The host HLA-A*02 allele is associated with the response to pegylated interferon and ribavirin in patients with chronic hepatitis C virus infection.

Human leukocyte antigen (HLA) alleles are associated with both the progression of chronic hepatitis C (CHC) and the sustained virological response (SVR) to antiviral therapy. HLA-A*02 is the most common HLA allele in people of European/Caucasian descent and the Chinese and Japanese population. Therefore, we investigated whether HLA-A*02 expression is associated with disease outcome in Chinese CHC patients. Three hundred thirty-one treatment-naïve CHC patients were recruited in this study. The expression of HLA-A*02 was tested by FACS and LABType SSO assays. All patients were treated weekly with pegylated interferon plus ribavirin (PEG-IFN/RBV) according to a standard protocol. Virological response was assessed by TaqMan assay at the 4th, 12th, 24th, and 48th week of therapy, and again at the 24th week post-therapy. By the end of the study, 293 CHC patients, including 144 HLA-A*02-positive patients and 149 HLA-A*02-negative patients, were evaluable for analysis. There were no statistical differences in clinicopathological parameters between HLA-A*02-positive and negative patients before antiviral therapy (P > 0.05). The HLA-A*02-positive patients had a higher rapid virological response (RVR, 74.3 % versus 62.4 %, P = 0.03) and SVR (78.5 % versus 64.4 %, P = 0.01) and a lower relapse rate (4.2 % versus 11.9 %, P = 0.03) than HLA-A*02-negative patients. Multivariable logistic regression analysis showed that HLA-A*02 expression, liver fibrosis stages

Toxicity of sodium fluoride to Caenorhabditis elegans.

OBJECTIVE: To investigate the toxic effect of sodium fluoride (NaF) on the nematode Caenorhabditis elegans (C. elegans). METHODS: Adult C. elegans were exposed to different concentrations of NaF (0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L) for 24 h. To assess the physiological effects of NaF, the brood size, life span, head thrashes, and body bend frequency were examined. Reactive oxygen species (ROS) and cell apoptosis were detected as parameters of biochemical response. The gene expressions were determined by real-time polymerase chain reaction (PCR) to assess the molecular-level response. RESULTS: At the physiological level, the brood size of C. elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 6%, 26%, and 28% respectively in comparison with the control group. The maximum life spans of C. elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 3 days and 5 days, respectively. Head thrashes and body bend frequency both decreased with increasing concentrations of NaF. At the biochemical level, the production of ROS and the incidence of cell apoptosis increased with increasing concentrations of NaF (P < 0.05). At the molecular level, different concentrations of NaF exposure raised the expression of stress-related genes, such as hsp16.1, sod-3, ctl-2, dhs-28, gst-1, and cep-1. CONCLUSION: NaF exposure could induce multiple biological toxicities to C. elegans in a concentration-dependent manner. These toxicities may be relevant to the oxidative stress induced by increased ROS production and accumulation in C. elegans.

[Preparation and in vitro evaluation of pH-sensitive TAT peptide conjugated micelles].

Doxorubicin loaded micelles were prepared by film-hydration method using stearyl sulfadiazine (SA-SD) which is pH sensitive, methoxy (polyethylene glycol)-2000-1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (mPEG-DOPE) and transactivator of transcription (TAT) peptide conjugated PEG-DOPE. Mean diameter of the pH-sensitive micelles was about 20 nm with a (99.1 +/- 2.1) % drug entrapment efficiency at pH 7.4. Flow cytometry studies revealed that the simple TAT micelles was taken up rapidly at the same level at pH 6.8 and pH 7.4. However, the pH-sensitive micelles entered the tumor cell less at pH 7.4 and significantly increase at pH 6.8. After 1 h incubation at pH 6.8, the amount of the pH-sensitive micelles taken up by cancer cell 4T1 was almost similar to simple TAT micelles. The confocal microscopy indicated that the pH-sensitive micelles entered the 4T1 cells at pH 6.8 more than at pH 7.4. It was indicated that the pH-sensitive micelles could shield TAT peptide at normal pH 7.4 and deshield it at pH 6.8. Hence, TAT peptides lead the drug-loaded micelles into the tumor cells and killed them selectively. The pH-sensitive micelle may provide a novel strategy for design of cancer targeting drug delivery system.

Changes in notifiable infectious disease incidence in China during the COVID-19 pandemic.

Nationwide nonpharmaceutical interventions (NPIs) have been effective at mitigating the spread of the novel coronavirus disease (COVID-19), but their broad impact on other diseases remains under-investigated. Here we report an ecological analysis comparing the incidence of 31 major notifiable infectious diseases in China in 2020 to the average level during 2014-2019, controlling for temporal phases defined by NPI intensity levels. Respiratory diseases and gastrointestinal or enteroviral diseases declined more than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Early pandemic phases with more stringent NPIs were associated with greater reductions in disease incidence. Non-respiratory diseases, such as hand, foot and mouth disease, rebounded substantially towards the end of the year 2020 as the NPIs were relaxed. Statistical modeling analyses confirm that strong NPIs were associated with a broad mitigation effect on communicable diseases, but resurgence of non-respiratory diseases should be expected when the NPIs, especially restrictions of human movement and gathering, become less stringent.

Epidemiological Characteristics of Notifiable Infectious Diseases among Foreign Cases in China, 2004-2017.

OBJECTIVE: We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases. METHODS: We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System (NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed. RESULTS: A total of 67,939 cases of 33 different infectious diseases were reported among foreigners. These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus (HIV) of 18,713 cases, hepatitis B (6,461 cases), hand, foot, and mouth disease (6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces. CONCLUSIONS: This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.

Impact of Dentinal Tubule Orientation on Dentin Bond Strength.

This study aimed to determine the impact of dentinal tubule orientation on dentin bond strength to provide a reference for clinical cavity preparation in resin-bonded restoration. Patients aged 13-16 years were selected, including 18 males and 21 females. Forty-eight human maxillary first premolars from orthodontic extractions were chosen to prepare the test models with the dentinal tubule orientations perpendicular and parallel to the bonding substrate. The test models in the vertical and parallel groups were divided into three groups: total-etching with 20% phosphoric acid, total-etching with 35% phosphoric acid and self-etching, with the dentinal tubule surfaces bonded with composite resin blocks in each group. After the standard test models of dentinal tubule-composite resin blocks were placed in distilled water and stored at 37°C for 24 h, shearing tests were performed using a universal material testing machine at a crosshead speed of 0.5 mm/min. The bond strength values in the vertical group were 19.33±1.59 MPa for the 20% phosphoric acid group, 21.39±2.34 MPa for the 35% phosphoric acid group, and 16.88±1.54 MPa for the self-etching group. The bond strength values in the parallel group were 24.53±1.99 MPa for the 20% phosphoric acid group, 25.16±2.88 MPa for the 35% phosphoric acid group, and 20.83±1.99 for the self-etching group. After using same total-etching adhesive, the shear bond strength of the parallel group was higher than that of the vertical group, and the difference was statistically significant (P<0.05). Regardless of vertical group or parallel group, the difference in the bond strength value between the total-etching groups and the self-etching group was statistically significant (P<0.05). It was concluded that the dentin bonding substrate which was parallel to the direction of the dentin tubule achieved an improved bond strength; the total-etching adhesives achieved higher bond strengths in dentin bond than the self-etching adhesives.

[Meta-analysis of the condylar position with mandibular deviation].

PURPOSE: This study was aimed to analyze the differences of condylar position between the mandibular deviation and the individual normal occlusion. METHODS: Databases of PubMed,Embase,CNKI ,Wanfang ,VIP and CBL were searched for the relevant articles about condylar position with mandibular deviation. The deadline was June 2017.Data quality evaluation and extraction were independently conducted by two authors. Then meta analysis was performed using Rev Man 5.3 software. RESULTS: Six articles on controlled study of the condylar position in patients with mandibular deviation and individuals with normal occlusion were included. 122 patients had mandibular deviation and 110 had normal occlusion. Meta analysis results showed that the condylar superior space[MD=-0.38,95%CI(-0.74,-0.01),P=0.04]and anterior space[MD=-0.72,95%CI(-0.99,-0.04),P＜0.00001]of the deviation side in mandibular deviation group were significantly greater than that of the opposite side; The condylar posterior space[MD=-0.35,95%CI(0.25,0.45),P＜0.00001]of the deviation side in mandibular deviation group was significantly smaller than that of the opposite side. The condylar posterior space of deviation side[MD=-0.58,95%CI(-0.88,-0.28),P=0.0002],opposite side[MD=-0.30,95%CI(-0.59,-0.00),P=0.05] and the anterior space of opposite side[MD=-0.85,95%CI(-1.58,-0.13),P=0.02] in the mandibular deviation group was significantly smaller than that in the individuals with normal occlusion; the differences were statistically significant. There was no significant difference in the condylar superior space between the deviation side[MD=-0.56,95%CI(-1.14,0.02),P=0.06] and the opposite side[MD=-0.58,95%CI(-1.27,0.10),P=0.10] and the anterior space[MD=-0.05,95%CI(-0.35,0.46),P=0.80]in deviation side in the mandibular deviation group ,comparing with individuals with normal occlusion. CONCLUSIONS: The condylar position of deviation side in patients with mandibular deviation is posterior and inferior, comparing with the opposite side. The condylar position of deviation side in patients with mandibular deviation is posterior, comparing with the individuals with normal occlusion.

Organocatalysts wrapped around by poly(ethylene glycol)s (PEGs): a unique host-guest system for asymmetric Michael addition reactions.

Asymmetric Michael addition reactions of unmodified ketones to nitroalkenes were performed in PEGs catalyzed by novel pyrrolidinyl-thioimidazolium salts to give products in up to 97% yield and 99% enantioselectivity; ESI mass spectrometric detection for the first time gave evidence of the presence of the PEG-organocatalyst host-guest complex.

Histone demethylase KDM2B inhibits the chondrogenic differentiation potentials of stem cells from apical papilla.

Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSCs differentiation. Previous studies determined that KDM2B can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2B is involved in the other cell lineages differentiation of MSCs. Here we used the stem cells from apical papilla (SCAPs) to study the role of KDM2B on the chondrogenic differentiation potentials in MSCs. In this study, Gain- and loss-of-function assays were applied to investigate the role of KDM2B on the chondrogenic differentiation. Alcian Blue Staining and Quantitative Analysis were used to investigate the synthesis of proteoglycans by chondrocytes. Real-time RT-PCR was used to detect the expressions of chondrogenesis related genes. The Alcian Blue staining and Quantitative Analysis results revealed that overexpression of KDM2B decreased the proteoglycans production, and real-time RT-PCR results showed that the expressions of the chondrogenic differentiation markers, COL1, COL2 and SOX9 were inhibited by overexpression of KDM2B in SCAPs. On the contrary, depletion of KDM2B increased the proteoglycans production, and inhibited the expressions of COL1, COL2 and SOX9. In conclusion, our results indicated that KDM2B is a negative regulator of chondrogenic differentiation in SCAPs and suggest that inhibition of KDM2B might improve MSC mediated cartilage regeneration.

Enriched trimethylation of lysine 4 of histone H3 of WDR63 enhanced osteogenic differentiation potentials of stem cells from apical papilla.

INTRODUCTION: Dental tissue-derived mesenchymal stem cells (MSCs) are a reliable cell source for dental tissue regeneration. However, the molecular mechanisms underlying their directed differentiation remain unclear, thus limiting their use. Trimethylation of lysine 4 of histone H3 (H3K4Me3) correlates with gene activation and osteogenic differentiation. We used stem cells from apical papilla (SCAPs) to investigate the effects of genomic changes in H3K4Me3 modification at gene promoter regions on MSC osteogenic differentiation. METHODS: ChIP-on-chip assays were applied to compare the H3K4Me3 profiles at gene promoter regions of undifferentiated and differentiated SCAPs. Alkaline phosphatase activity assay, alizarin red staining, quantitative analysis of calcium, the expressions of osteogenesis-related genes, and transplantation in nude mice were used to investigate the osteogenic differentiation potentials of SCAPs. RESULTS: In differentiated SCAPs, 119 gene promoters exhibited >2-fold increases of H3K4Me3; in contrast, the promoter regions of 21 genes exhibited >2-fold decreases of H3K4Me3. On the basis of enriched H3K4Me3 and up-regulated gene expression on the osteogenic differentiation of SCAPs, WDR63 may be a potential regulator for mediating SCAP osteogenic differentiation. Through gain-of-function and loss-of-function studies, we discovered that WDR63 enhances alkaline phosphatase activity, mineralization, and the expression of BSP, OSX, and RUNX2 in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis is triggered by activated WDR63. CONCLUSIONS: These results indicate that WDR63 is a positive enhancer for SCAP osteogenic differentiation and suggest that activation of WDR63 signaling might improve tissue regeneration mediated by MSCs of dental origin.

Fate of biopolymers during rapeseed meal and wheat bran composting as studied by two-dimensional correlation spectroscopy in combination with multiple fluorescence labeling techniques.

Detailed knowledge of the molecular events during composting is important in improving the efficiency of this process. By combining two-dimensional Fourier transform infrared (FTIR) correlation spectroscopy and multiple fluorescent labeling, it was possible to study the degradation of biopolymers during rapeseed meal and wheat bran composting. Two-dimensional FTIR correlation spectroscopy provided structural information and was used to deconvolute overlapping bands found in the compost FTIR spectra. The degradation of biopolymers in rapeseed meal and wheat bran composts followed the sequence: cellulose, heteropolysaccharides, and proteins. Fluorescent labeling suggested that cellulose formed an intact network-like structure and the other biopolymers were embedded in the core of this structure. The sequence of degradation of biopolymers during composting was related to their distribution patterns.

Experimental research of RB94 gene transfection into retinoblastoma cells using ultrasound-targeted microbubble destruction.

The purpose of this study was to explore the transfection of the recombinant expression plasmid pEGFP-C1/RB94 into human retinoblastoma cells (HXO-Rb44) using ultrasound-targeted microbubble destruction (UTMD). pEGFP-C1/RB94 was transfected into HXO-Rb44 in vitro by UTMD, with liposome as the positive control. After 24 to 72 h, the expression of the reporter gene enhanced green fluorescent protein (EGFP) was observed using fluorescent microscopy and flow cytometry. The cell viability of HXO-Rb44 was measured by a MTT assay. The mRNA and proteins of RB94, caspase-3 and Bax were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Moreover, the apoptosis rate and cell cycle progression of the cells were detected by flow cytometry. This study demonstrated that UTMD can enhance the transfection efficiency of RB94, which has an obvious impact on the inhibition of the growth process of retinoblastoma cells, suggesting that the combination of UTMD and RB94 compounds might be a useful tool for use in the gene therapy of retinoblastoma.

Study of aggregation induced emission of cyano-substituted oligo (p-phenylenevinylene) by femtosecond time resolved fluorescence.

The aggregation induced emission (AIE) mechanism of the cyano-substituted oligo (p-phenylenevinylene)1,4-bis [1-cyano-2-(4-(diphenylamino) phenyl) vinyl] benzene (TPCNDSB) is investigated by time resolved fluorescence technique. By reconstructing the time resolved emission spectra (TRES), it is found that in solvent of low polarity, the emission is mainly from the local emission (LE) state with high quantum yield, but in high polarity solvent, the emission is mainly from the intramolecular charge transfer (ICT) state, which is a relatively dark state, with low quantum yield. In crystal form, the restriction of transfer from LE state to ICT state results in efficient AIE.

Protein adsorption under electrical stimulation of neural probe coated with polyaniline.

Polyaniline (PANI) nanoparticles were successfully polymerized on the surface of Pt electrode to form nanostructured films. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) micrographs showed that the just-synthesized films were compact with diameter of nanoparticles on films about 50 and 30nm for HClO(4) and citric acid doped PANI films, respectively. And the surface of the electrode was coated completely with PANI films. After electrical stimulation for 1 month in 0.9% sodium chloride solution, there were no fissures appearing on PANI films. The compact film would act as a protecting membrane of the Pt surface, and is suitable to be used as the electrode coating for long-time performance. The time frame of human plasma fibronectin (FN) and bovine serum albumin (BSA) adsorption illustrated that electrical stimulation enhanced the amount of protein adsorption on PANI films up to 1.7-fold increase as compared to that without electrical stimulation. The SEM images of BSA adsorption for 120min indicated that electrical stimulation might initiate the aggregation of BSA, and the nanostructure of the PANI films could inhibit the aggregation. We also found that the protein adsorption decreased conductivity of PANI films, which maybe due to the protein barriers formed on them. These results provided a good reference for the use of conducting polymers as neural probe coating.