Label-Free Colorimetric Method for Detection of Vibrio parahaemolyticus by Trimming the G-Quadruplex DNAzyme with CRISPR/Cas12a.

Vibrio parahaemolyticus (V. parahaemolyticus), which may cause gastrointestinal disorders in humans, is a pathogen commonly found in seafood. There are many methods for detecting V. parahaemolyticus, yet they have some shortcomings, such as high cost, labor-intensiveness, and complicated operation, which are impractical for resource-limited settings. Herein, we present a sequence-specific, label-free, and colorimetric method for visual detection of V. parahaemolyticus. This method utilizes CRISPR/Cas12a to specifically recognize the loop-mediated isothermal amplification (LAMP) products for further trans-cleaving the G-quadruplex DNAzyme and depriving its peroxidase-mimicking activity. In this way, the results can be directly observed with the naked eyes via the color development of 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS2-), which displays colorless for positive samples while green for target-free samples. We term such Cas12a-crRNA preventing ABTS2- from developing color by trimming the G-quadruplex DNAzyme as Cascade. The proposed method can detect 9.8 CFU (per reaction) of pure cultured V. parahaemolyticus, and the sensitivity is comparable to real-time LAMP. It has been applied for practical use and showed the capability to detect 6.1 × 102 CFU/mL V. parahaemolyticus in shrimp samples. Based on this, the newly established Cascade method can be employed as a universal biosensing strategy for pathogenic bacterial testing in the field.

Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson's disease symptoms by regulating brain amyloid ß1-42 level.

Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson's disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aß1-42 and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aß1-42 in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p-c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aß1-42 level and decreased brain Aß1-42 level.

The paternal genetic structure of Jingpo and Dai in southwest China.

Yunnan province harbours substantial genetic, cultural and linguistic diversity, with the largest number of Aborigines in China, but the relationship among these Aborigines remains enigmatic. This study genotyped 45 Y chromosomal single nucleotide polymorphisms (SNPs) of 500 males from two aboriginal cross-border populations, Jingpo and Dai, from Dehong, Yunnan. It is reported that Haplogroup O2a2b1a1-M117 is the dominant lineage in both Jingpo and Dai. The Jingpo people show affinity with Tibeto-Burman speaking populations with a relatively high frequency of Haplogroup D-M174, and the Dai people are generally genetically similar with Tai-Kadai speaking populations with high frequencies of Haplogroup O1a-M119 and O1b1a1a-M95, which is consistent with their language classification.

[The derivation and validation of a prediction rule for differential diagnosis of thyroid nodules].

OBJECTIVE: To set up a prediction rule for the pro-operative differential diagnosis of thyroid nodules and evaluate its clinical value. METHODS: All patients of thyroid nodules underwent thyroid operations in Changzheng hospital from June, 1997 to July, 2012 were included in this study. They were randomly divided into the derivation cohort (2/3) and the validation cohort (1/3). A prediction rule was developed based on the logistic regression model and the scoring system was established in accordance with assigning of the value of each variable ß in the model. The prediction consistency, discriminatory power and diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. RESULTS: A total of 13 980 patients were enrolled in the study with 9195 in the derivation cohort and 4785 in the validation cohort. The prediction rule consisted of 18 variables, which were gender, clinical manifestations including fever, neck sore, neck mass, palpitation and sweating, serum level of thyroid stimulating hormone (TSH) , free triiodothyronine (FT3) , thyroid peroxidase antibody (TPOAb) , thyroglobulin antibody (TgAb) , thyroglobulin (Tg) , calcitonin and carcinoembryonic antigen (CEA) , ultrasonography features including nodules number, location, size, boundaries and ethological patterns and the presence and patterns of lymph nodes. The model showed good calibration consistency (P = 0.437) and discrimination power (area under the receiver operating characteristic curve was 0.928) in the derivation cohort. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the model were 89.3%, 81.5%, 83.2%, 56.8%, 96.6%, 4.83 and 0.13, respectively. CONCLUSION: The prediction rule and its scoring system established in the study are efficacious for the calibration and discrimination of thyroid nodules in Chinese population, which could be a useful tool for the pro-operative risk stratification.

Identification of Clec7a as the therapeutic target of rTMS in alleviating Parkinson's disease: targeting neuroinflammation.

Parkinson's disease (PD) is a neurodegenerative disease. Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic tool in PD. High-throughput sequencing was performed to screen potential therapeutic targets in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. The candidate gene, Clec7a, was screened out and validated. Clec7a is a pattern recognition receptor involved in neuroinflammation. The higher expression of Clec7a was observed in the substantia nigra (SN) and striatum of PD rats with dopaminergic neurons damage and was mainly localized in the microglial. Adeno-associated virus (AAV)-mediated specific knockdown of Clec7a in microglial alleviated 6-OHDA induced motor deficits and nigrostriatal dopaminergic neuron damage of rats, as evidenced by the increase of tyrosine hydroxylase (TH) -positive neurons in SN, as well as dopaminergic nerve fibers in the striatum. Clec7a knockdown restrained the neuroinflammation by suppressing inflammatory factors (IFN-γ, TNF-α, IL-1ß, IL-18, and IL-6) release in SN, which might result from enhanced Arg-1 expression (M2 polarization) and defective inducible nitric oxide synthase (iNOS) expression (M1 polarization). The same phenomena were also observed in the LPS inflammatory rat model of PD. In vitro, α-synuclein fibrils induced upregulation of Clec7a expression and microglia polarization to a pro-inflammatory state of BV2 cells, leading to increased release of cytokines. However, Clec7a knockdown reversed those changes and induced a shift to an anti-inflammatory phenotype in BV2 cells. In conclusion, our study suggested that Clec7a was involved in PD pathogenesis, and its inhibition might protect rats from PD by depressing neuroinflammation through microglial polarization.

Improving the regional Y-STR haplotype resolution utilizing haplogroup-determining Y-SNPs and the application of machine learning in Y-SNP haplogroup prediction in a forensic Y-STR database: A pilot study on male Chinese Yunnan Zhaoyang Han population.

Improving the resolution of the current widely used Y-chromosomal short tandem repeat (Y-STR) dataset is of great importance for forensic investigators, and the current approach is limited, except for the addition of more Y-STR loci. In this research, a regional Y-DNA database was investigated to improve the Y-STR haplotype resolution utilizing a Y-SNP Pedigree Tagging System that includes 24 Y-chromosomal single nucleotide polymorphism (Y-SNP) loci. This pilot study was conducted in the Chinese Yunnan Zhaoyang Han population, and 3473 unrelated male individuals were enrolled. Based on data on the male haplogroups under different panels, the matched or near-matching (NM) Y-STR haplotype pairs from different haplogroups indicated the critical roles of haplogroups in improving the regional Y-STR haplotype resolution. A classic median-joining network analysis was performed using Y-STR or Y-STR/Y-SNP data to reconstruct population substructures, which revealed the ability of Y-SNPs to correct misclassifications from Y-STRs. Additionally, population substructures were reconstructed using multiple unsupervised or supervised dimensionality reduction methods, which indicated the potential of Y-STR haplotypes in predicting Y-SNP haplogroups. Haplogroup prediction models were built based on nine publicly accessible machine-learning (ML) approaches. The results showed that the best prediction accuracy score could reach 99.71% for major haplogroups and 98.54% for detailed haplogroups. Potential influences on prediction accuracy were assessed by adjusting the Y-STR locus numbers, selecting Y-STR loci with various mutabilities, and performing data processing. ML-based predictors generally presented a better prediction accuracy than two available predictors (Nevgen and EA-YPredictor). Three tree models were developed based on the Yfiler Plus panel with unprocessed input data, which showed their strong generalization ability in classifying various Chinese Han subgroups (validation dataset). In conclusion, this study revealed the significance and application prospects of Y-SNP haplogroups in improving regional Y-STR databases. Y-SNP haplogroups can be used to discriminate NM Y-STR haplotype pairs, and it is important for forensic Y-STR databases to develop haplogroup prediction tools to improve the accuracy of biogeographic ancestry inferences.

Association of Serum Nonesterified Fatty Acids with Cardiovascular Event in Patients with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) has been suggested to be associated with a high risk of cardiovascular diseases (CVD). The study aimed to evaluate the prognostic significance of nonesterified fatty acid (NEFA), also well known as free fatty acid, on predicting cardiovascular events in patients with CKD. METHODS: A total of 957 hospitalized patients with CKD in a stable clinical condition were enrolled at baseline. Then, the serum NEFA levels were measured. These included patients were prospectively followed up for a median of 10.2 years (range=0.4-11.5 years). We assessed whether serum NEFA levels at baseline can predict cardiovascular event during the follow-up. RESULTS: A total of 278 (29.1%) patients experienced cardiovascular events during follow-up. The Kaplan-Meier curve demonstrated that patients with higher serum NEFA levels (≥19.8 mg/dl) had a higher rate of cardiovascular events than patients with lower NEFA levels (<19.8 mg/dl). Multivariate Cox regression analysis suggested that elevated serum NEFA levels (HR=1.62; 95% CI 1.40-2.16, P<0.001) were independently associated with increased risk of cardiovascular events after correction for clinical confounding factors. CONCLUSION: Elevated serum NEFA levels were associated with higher risk of cardiovascular events and may be a new parameter predicting cardiovascular events in patients with CKD, which may strengthen its potential effect in clinical practice.

Co-delivery of antibiotic and baicalein by using different polymeric nanoparticle cargos with enhanced synergistic antibacterial activity.

To evaluate the effect of polymer structures on their unique characteristics and antibacterial activity, this study focused on developing amphiphilic copolymers by using three different molecules through RAFT polymerization. Three amphiphilic copolymers, namely, PBMA-b-(PDMAEMA-r-PPEGMA) (BbDrE), (PBMA-r-PDMAEMA)-b-PPEGMA (BrDbE), and PBMA-r-PDMAEMA-r-PPEGMA (BrDrE), are successfully self-assembled into spherical or oval shaped nanoparticles in aqueous solution and remain stable in PBS, LB, and 10% FBS solutions for at least 3 days. The critical micelle concentrations are 0.012, 0.025, and 0.041 mg/mL for BbDrE, BrDbE, and BrDrE, respectively. The zeta potential values under pH 5.5 and pH 7.4 conditions are 3.18/0.19, 8.57/0.046, and 2.54/-0.69 mV for BbDrE, BrDbE, and BrDrE nanoparticles, respectively. The three copolymers with similar monomer compositions show similar molecular weight and thermostability. Baicalein (BA) and ciprofloxacin (CPX) are encapsulated into the three nanoparticles to obtain BbDrE@BA/CPX, BrDbE@BA/CPX, and BrDrE@BA/CPX nanocomposites, with LC values of 63.9/78.3, 63.9/74.7, and 55.3/64.8, respectively. The two drugs are released from the three drug-loaded nanocomposites with 60%-95% release in pH 5.5 over 24 h and 15%-30% release in pH 7.4. The drug-loaded nanocomposites show synergistic antibacterial activity than the naked drug (2-8 fold reduction for CPX) or single drug-loaded nanocomposites (4-8 fold reduction for CPX) against Pseudomonas aeruginosa and Staphylococcus aureus. The drug-loaded nanocomposites inhibit the formation of bacterial biofilms above their MIC values and eliminate bacterial biofilms observed by fluorescent microscope. Finally, the nanocomposites improve the healing of infection induced by P. aeruginosa and S. aureus on rat dermal wounds. These results indicate that antimicrobial agents with different structures could be an alternative treatment strategy for bacteria-induced infection.

Genetic Reconstruction and Forensic Analysis of Chinese Shandong and Yunnan Han Populations by Co-Analyzing Y Chromosomal STRs and SNPs.

Y chromosomal short tandem repeats (Y-STRs) have been widely harnessed for forensic applications, such as pedigree source searching from public security databases and male identification from male-female mixed samples. For various populations, databases composed of Y-STR haplotypes have been built to provide investigating leads for solving difficult or cold cases. Recently, the supplementary application of Y chromosomal haplogroup-determining single-nucleotide polymorphisms (SNPs) for forensic purposes was under heated debate. This study provides Y-STR haplotypes for 27 markers typed by the Yfiler™ Plus kit and Y-SNP haplogroups defined by 24 loci within the Y-SNP Pedigree Tagging System for Shandong Han (n = 305) and Yunnan Han (n = 565) populations. The genetic backgrounds of these two populations were explicitly characterized by the analysis of molecular variance (AMOVA) and multi-dimensional scaling (MDS) plots based on 27 Y-STRs. Then, population comparisons were conducted by observing Y-SNP allelic frequencies and Y-SNP haplogroups distribution, estimating forensic parameters, and depicting distribution spectrums of Y-STR alleles in sub-haplogroups. The Y-STR variants, including null alleles, intermedia alleles, and copy number variations (CNVs), were co-listed, and a strong correlation between Y-STR allele variants ("DYS518~.2" alleles) and the Y-SNP haplogroup QR-M45 was observed. A network was reconstructed to illustrate the evolutionary pathway and to figure out the ancestral mutation event. Also, a phylogenetic tree on the individual level was constructed to observe the relevance of the Y-STR haplotypes to the Y-SNP haplogroups. This study provides the evidence that basic genetic backgrounds, which were revealed by both Y-STR and Y-SNP loci, would be useful for uncovering detailed population differences and, more importantly, demonstrates the contributing role of Y-SNPs in population differentiation and male pedigree discrimination.

Title: Developmental validation of Y-SNP pedigree tagging system: A panel via quick ARMS PCR.

The Y chromosomal short tandem repeats (Y-STRs) have been used widely to establish paternal relatedness and examine sub-structures in different geographical regions. However, the applications of Y-STRs showed their limitations when it comes to resolving the complicated relationships within close relatives or among unrelated individuals from different geographic areas. Here, we overcome these limitations by introducing a new strategy for Y-SNP multiplex typing using rapid ARMS (amplification-refractory mutation system) PCR. Newly developed Y-SNP Pedigree Tagging System is able to profile 24 Y-SNPs in a single reaction while the whole process takes 4-5 hours. The panel precisely defines the 11 haplogroups (E-M96, D-JST021355, N-M231, C-M130, O-P186, I-M170, IJ-M429, K-M9, QR-M45, G-M201, and IJK-M522) and 13 sub-haplogroups (D1a1a1-N1, D1a2a-P47, C2-M217, N1a1-M46, O1a-M119, O1b-M268, O1b2-M176, O2-M122, O2a1-KL1, O2a2-P201, O2a2b-P164, O2a2a1a2-M7 and O2a2b1a1-M117). This system could contribute to providing the haplogroup affiliation of unknown pedigree and resolving the sub-structures of East Asian populations. In this study, the multiplex system was validated for: ability to detect degraded DNA, sensitivity, species specificity, reproducibility/repeatability, stability, performance in different scenarios, mixture studies, PCR amplification conditions, and population surveys. The Y-SNP information showed a consistent pattern within 40 father-son or brother-brother pairs. The results of this multiplex system showed the different distribution patterns of male donors from two Chinese Han populations. In this study, we try to discriminate the suspect's pedigree on the level of Y-SNP haplogroups. These results show that Y-SNP Pedigree Tagging System is a robust and reliable amplification kit which can be used for male haplogroup determination.

Two-dimensional differential in-gel electrophoresis for identification of gastric cancer-specific protein markers.

Gastric cancer is the second most common fatal malignancy in the world. Proteomics studies of clinical tumor samples have led to the identification of specific protein markers of gastric cancer detection and better understanding the carcinogenesis of gastric cancer. Gastric cancer tissue of epithelial origin and adjacent normal mucosa were examined in pair by fluorescence 2-D differential in-gel electrophoresis proteomics analysis utilizing 2-D PAGE protein separation. Intensity changes of 33 spots were detected with statistical significance. Twenty-two out of the 33 spots were identified by MALDI-TOF MS or MS/MS. Of the 9 up-regulated proteins, 7 were identified, including heat shock protein 60 (HSP60), mutant desmin, effector cell proteinase receptor 1 splice form 1b, hypothetical protein, unnamed protein product, and manganese superoxide dismutase (MnSOD), a protein similar to alpha-actin. Of the 20 down-regulated proteins, 16 were identified, including selenium binding protein 1, fibrinogen gamma, HSP27, tubulin alpha 6, zinc finger protein 160, prostaglandin F synthase, and eukaryotic translation elongation factor 1 alpha 1. Our results suggest that MnSOD may be a potential serum marker for molecular diagnosis of gastric carcinoma, and DIGE is a useful technique for screening differentially expressed proteins in cancer tissues.

Administration of Repetitive Transcranial Magnetic Stimulation Attenuates Aß 1-42-Induced Alzheimer's Disease in Mice by Activating ß-Catenin Signaling.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and painless technique that has been applied for the treatments of diverse neurodegenerative disorders. In the current study, its anti-Alzheimer's disease (AD) effect was assessed and the mechanism driving the effect was explored. The AD symptoms were induced via the intracranial injection of Aß 1-42 in mice and then treated with rTMS of 1 Hz or 10 Hz. The anti-AD effect of rTMS was assessed by Morris water maze (MWM), histological staining and western blotting. The results showed that rTMS administrations of both frequencies improved the cognitive function and suppressed neuron apoptosis in AD mice. Moreover, the treatment also increased the brain BDNF, NGF, and doublecortin levels, which represented the increased viability of neurons by rTMS. The injection of Aß 1-42 also increased the expressions of p-GSK-3ß, p-Tau, and p-ß-catenin and suppressed the level of total ß-catenin. After the treatments of rTMS, the level of ß-catenin was restored, indicating the activation of ß-catenin signaling. In conclusion, the findings outlined in the current study demonstrated that the anti-AD effect of rTMS was associated with the activation of ß-catenin, which would promote the survival of neurons.

Magnetic and self-healing chitosan-alginate hydrogel encapsulated gelatin microspheres via covalent cross-linking for drug delivery.

In order to broaden the abilities of injectable hydrogel scaffolds, a self-healing chitosan/alginate hydrogel encapsulated with magnetic gelatin microspheres (MGMs) was prepared for anti-cancer drug delivery and soft tissue engineering. The hydrogel was formulated by cross-linking carboxyethyl chitosan (CEC) and oxidized alginate (OAlg) via the Schiff-base reaction. To strengthen the mechanical and biological capabilities of hydrogel, MGMs containing 5-fluorouracil (5-Fu) were prepared by an emulsion cross-linking method. In vitro gelation time, swelling ratio, degradation, compressive modulus and rheological behaviors were tested to monitor the effect of MGMs on the CEC-OAlg hydrogel. With a concentration of 30 mg/mL MGMs, the composite hydrogel provided with the suitable performance and showed excellent self-healing ability under physiological condition. Moreover, this composite hydrogel showed the sustained in vitro drug release compared with control MGMs and CEC-OAlg hydrogel. Our results demonstrated that this magnetic and self-healing CEC-OAlg hydrogel scaffold encapsulated MGMs containing 5-Fu was expected to be a platform for drug delivery and soft tissue engineering.

Lithium manganese(II) diaqua-boro-phosphate monohydrate.

The title compound, LiMn(H(2)O)(2)[BP(2)O(8)]·H(2)O, is built up of an open framework of helical borophosphate ribbons inter-connected by MnO(4)(H(2)O)(2) octa-hedra, forming one-dimensional channels along [001] occupied by Li(+) cations and disordered H(2)O mol-ecules (site occupancy 0.5). The Li cations reside in two partially occupied sites [occupancies = 0.42 (3) and 0.289 (13)] near the helices.

[Interventions on the exposure of non-smoking pregnant women to passive smoking].

OBJECTIVE: To investigate the extent of exposure of non-smoking pregnant women to passive smoking; to undertake interventions on the knowledge, attitudes and behaviors of those women toward passive smoking; and to evaluate the effectiveness of the interventions. METHODS: A total of 128 non-smoking pregnant women participated in the survey. Their knowledge, attitudes and behaviors towards passive smoking were measured by a self-administered questionnaire. A sixteen-week intervention was undertaken. RESULTS: The knowledge and attitudes of the non-smoking pregnant women towards passive smoking improved significantly, as well as their attempts to avoid exposure to the passive smoking brought by their smoking husbands or other family members. Telephone counseling, booklets and doctors' advices were the most acceptable approaches of health education. CONCLUSION: The comprehensive interventions are effective for improving the knowledge, attitudes and behaviors of non-smoking women toward passive smoking.

Injectable polysaccharide hydrogel embedded with hydroxyapatite and calcium carbonate for drug delivery and bone tissue engineering.

To meet the progressive requirements for bone regeneration purpose, injectable hydrogels have attracted increasing attention in tissue regeneration and local drug delivery applications. In this study, we report a facile method to prepare injectable and degradable polysaccharide-based hydrogels doubly integrated with hydroxyapatite (HAp) nanoparticles and calcium carbonate microspheres (CMs) under physiological condition. The mechanism of cross-linking is attributed to the Schiff-base reaction between amino and aldehyde groups of carboxymethyl chitosan (CMCS) and oxidized alginate (OAlg), respectively. Synchronously, tetracycline hydrochloride (TH) loaded CMs were fabricated by the precipitation reaction with an average diameter of 6.62 µm. To enhance bioactive and mechanical properties, nano-HAp and CMs containing TH were encapsulated into the polysaccharide-based hydrogel to form injectable gel scaffolds for imitation of bone niche. The gelation time, morphology, mechanical properties, swelling ratio and in vitro degradation of the gel scaffolds could be controlled by varying HAp and CMs contents. Moreover, the composite gel scaffolds had good sustained drug release and antibacterial properties, as confirmed by drugs release calculation and antibacterial evaluation. In addition, the gel scaffolds were found to be self-healing due to dynamic equilibrium of the Schiff-base linkages. These results suggested that the prepared composite gel scaffolds hold great potential for drug delivery and regeneration of irregular bone defects.

Dynamical release nanospheres containing cell growth factor from biopolymer hydrogel via reversible covalent conjugation.

For practical adipose regeneration, the challenge is to dynamically deliver the key adipogenic insulin-like growth factors in hydrogels to induce adipogenesis. In order to achieve dynamic release, smart hydrogels to sense the change in the blood glucose concentration is required when glucose concentration increases. In this study, a heparin-based hydrogel has been developed for use in dynamic delivery of heparin nanospheres containing insulin-like growth factor. The gel scaffold was facilely prepared in physiological conditions by the formation of boronate-maltose ester cross-links between boronate and maltose groups of heparin derivatives. Due to its intrinsic glucose-sensitivity, the exposure of gel scaffold to glucose induces maltose functionalized nanospheres dissociation off hydrogel network and thereby could dynamically move into the microenvironment. The potential of the hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this dynamic hydrogel could support survival and proliferation of ASCs. This biocompatible coupling chemistry has the advantage that it introduces no potentially cytotoxic groups into injectable gel scaffolds formed and can create a more biomimetic microenvironment for drug and cell delivery, rendering them more suitable for potential in vivo biomedical applications. All these results indicate that this biocompatible gel scaffold can render the formulation of a therapeutically effective platform for diabetes treatment and adipose regeneration.

The synthetic retinoid CD437 selectively induces apoptosis in human lung cancer cells while sparing normal human lung epithelial cells.

The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induces apoptosis in a variety of cancer cells including lung cancer cells. Our previous studies have demonstrated that cancer cells with wild-type p53 are more sensitive to CD437 than those having mutant p53, although CD437 can induce both p53-dependent and -independent apoptosis. Because normal human lung epithelial cells have wild-type p53, the question arose as to whether they are also sensitive to CD437-induced apoptosis. To address this question, we compared and contrasted the effects of CD437 on apoptosis induction and the expression of several p53-regulated apoptosis-related genes between normal human lung epithelial cells and human lung cancer cells containing wild-type p53. CD437 induced apoptosis as evidenced by apoptotic morphological changes, increased DNA fragmentation, and activation of caspase cascades in two lung cancer cell lines but not in two normal human lung epithelial cells. CD437 selectively increased the p53 protein level and concomitantly induced the expression of several p53-regulated apoptosis-related genes including Bax, Fas, DR4, and DR5 only in the two lung cancer cell lines. Furthermore, the normal lung epithelial cells, which expressed constitutively higher levels of two antiapoptotic decoy receptors DcR1 and DcR2 than lung cancer cells, exhibited an increase in the expression of these receptors after CD437 treatment, whereas no increase was detected in lung cancer cells. These results predict a differential effect of CD437 on tumor and normal cells in vivo and strongly suggest that CD437 may be a useful agent for chemoprevention and/or treatment of human cancer, especially lung cancer.

A new computational model for human thyroid cancer enhances the preoperative diagnostic efficacy.

Considering the high rate of missed diagnosis and delayed treatments for thyroid cancer, an effective systematic model for the differential diagnosis is highly needed. Thus we analyzed the data on the clinicopathological characteristics, routine laboratory tests and imaging examinations in a cohort of 13,980 patients with thyroid cancer to establish a new diagnostic model for differentiating thyroid cancer in clinical practice. Here, we randomly selected two-thirds of the population to develop the thyroid malignancy risk scoring system (TMRS) for preoperative differentiation between thyroid cancer and benignant thyroid diseases, and then validated its differential diagnostic power in the rest one-third population. The 18 predictors finally enrolled in the TMRS included male gender, clinical manifestations (fever, neck sore, neck lump, palpitations or sweating), laboratory findings (TSH>1.56mIU/L, FT3>5.85pmol/L, TPOAb>14.97IU/ml, TgAb>48.00IU/ml, Tg>34.59µg/L, Ct>64.00ng/L, and CEA>0.41µg/L), and ultrasound features (tumor number≤ 23mm, site, size, echo texture, margins, and shape of neck lymphnodes). The TMRS is validated to be well-calibrated (P = 0.437) and excellently discriminated (AUC = 0.93, 95% CI [0.92, 0.94]), with an accuracy of 83.2%, a sensitivity of 89.3%, a specificity of 81.5%, positive and negative predictive values of 56.8% and 96.6%, positive and negative likelihood ratios of 4.83 and 0.13 in the development cohort, respectively. The TMRS highlights that this differential diagnostic system could help provide accurate preoperative risk stratification for thyroid cancer, and avoid unnecessary over- and under-treatment for such patients.

Expression of the high mobility group proteins HMGI(Y) correlates with malignant progression in Barrett's metaplasia.

Expression of the high mobility group proteins HMGI(Y) has been shown to be a marker of malignancy in thyroid and pancreatic lesions and to correlate significantly with malignant progression in the colon. The aim of this study was to determine whether HMGI(Y) expression is associated with malignant progression in Barrett's metaplasia (BM). Immunoperoxidase staining for HMGI(Y) was performed on sections of formalin-fixed paraffin-embedded endoscopic esophageal biopsies from 42 patients with BM. These consisted of 19 biopsies negative for dysplasia (ND), 16 with low-grade dysplasia (LGD)/indeterminate for dysplasia (IND), and 7 with high-grade dysplasia (HGD)/adenocarcinoma (CA). The percentage of positive cells was recorded, and nuclear HMGI(Y) immunoreactivity in >10% of the cells was considered positive. Statistical analysis was performed using Fisher's exact test. Positive HMGI(Y) staining was detected in 2 of 19 (11%) cases ND, 5 of 16 (30%) LGD/IND cases, and 7 of 7 (100%) HGD/CA cases. Biopsies with HGD/CA were significantly more likely to be positive for HMGI(Y) than biopsies ND (P < 0.0001) or with LGD/IND (P = 0.0046). We conclude that HMGI(Y) expression is significantly associated with malignant progression in BM. Additional studies are needed to determine whether BM biopsies that are ND or LGD/IND and positive for HMGI(Y) are more likely to progress to adenocarcinoma.