The role and molecular mechanism of gut microbiota in Graves' orbitopathy.

PURPOSE: Graves' orbitopathy (GO) is an autoimmune orbital disorder. Gut microbiota dysfunction plays a vital role in autoimmune diseases, including Graves' disease (GD) and GO. In the present study, we aimed to investigate the change of gut microbiota in GD/GO using mouse model. METHODS: The murine model of GD/GO was established by the challenge of adenovirus expressing thyroid-stimulating hormone (TSH) receptor (TSHR) (Ad-TSHR). The histological changes of orbital and thyroid tissues were analyzed by hematoxylin and eosin (H&E), Masson staining, and immunohistochemistry (IHC) staining. The fecal samples were collected for 16S rRNA gene sequencing and bioinformatics analysis. RESULTS: The GD/GO model was established successfully, as manifested as the broadened eyelid, exophthalmia and conjunctive redness, severe inflammatory infiltration among thyroid glands and between extraocular muscle space, hypertrophic extraocular muscles, elevated thyroxine (T4) and decreased TSH, and positive CD34, CD40, collagen I, and α-SMA staining. A total of 222 operational taxonomic units (OUTs) were overlapped between mice in the Ad-NC and Ad-TSHR groups. The microbial composition of the samples in the two groups was mainly Bacteroidia and Clostridia, and the Ad-NC group had a significantly lower content of Bacteroidia and higher content of Clostridia. KEGG orthology analysis results revealed differences in dehydrogenase, aspartic acid, bile acid, chalcone synthase, acetyltransferase, glutamylcyclotransferase, glycogenin, and 1-phosphatidylinositol-4-phosphate 5-kinase between two groups; enzyme commission (EC) analysis results revealed differences in several dehydrogenase, oxidase, thioxy/reductase between two groups; MetaCyc pathways analysis results revealed differences in isoleucine degradation, oxidation of C1 compounds, tricarboxylic acid (TCA) cycle IV, taurine degradation, and biosynthesis of paromamine, heme, colonic acid building blocks, butanediol, lysine/threonine/methionine, and histidine/purine/pyrimidine between two groups. CONCLUSION: This study induced a mouse model of GD/GO by Ad-TSHR challenge, and gut microbiota characteristics were identified in the GD/GO mice. The Bacteroidia and Clostridia abundance was changed in the GD/GO mice. These findings may lay a solid experimental foundation for developing personalized treatment regimens for GD patients according to the individual gut microbiota. Given the potential impact of regional differences on intestinal microbiota, this study in China may provide a reference for the global overview of the gut-thyroid axis hypothesis.

Water and oxygen co-induced microstructure relaxation and evolution in CH3NH3PbI3.

Owing to perovskite possessing the outstanding optoelectronic properties, perovskite-based solar cells show prominent performance. The stability of perovskite-based solar cells hampers the progress of commercialization, so it is important to understand the microstructure mechanism of perovskite degradation under the humidity and oxygen environmental conditions. In this study, a meaningful Debye-type dielectric relaxation was observed under water vapor and oxygen co-treatment conditions. Interestingly, the relaxation was not observed under water vapor or oxygen treatment individually. This new dielectric relaxation is identified as a direct result of dipole jump, and its activation energy was measured to be 630 ± 6 meV. According to photoelectron spectroscopy and 13C nuclear magnetic resonance data, we suggest that the dipoles are formed by CH3NH3+ (MA+) and superoxide (O2-), which originate from the distorted crystal lattice and water vapor-weakened hydrogen bonds of Pb-I cages. In addition, the activation energy fitted by dielectric relaxation might be the energy of ion migration. This study contributes to understanding the mechanism of perovskite degradation from the view of microstructure relaxation and evolution, and also provides a method for the analysis of ion migration energy.

Resection of the irradiated esophagus: the impact of lymph node yield on survival.

There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal (<9) or extensive (≥9) lymph node yield. Demographic, operative, and postoperative outcomes were compared between the groups. Kaplan-Meier analysis with the log rank test was used to compare survival between the yield groups. Cox proportional hazards model was used to determine the association between lymph node yield and survival. In total, 886 cases were included: 349 (39%) belonging to the minimal node group and 537 (61%) to the extensive group. Unadjusted 5-year survival was similar between the minimal and extensive groups, respectively (37.3% vs. 38.8%; P > 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66-0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ(2)=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01). Conclusion: The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

[Surgical management of elderly patients with medial wall pyriform sinus cancer].

Objective: To investigate the clinical efficacy of preoperative-, postoperative-radiotherapy and surgery for preserving laryngeal function in patient over 70 years of age with medial wall pyriform sinus cancer. Methods: Clinical data of 48 patients over 70 years of age with medial wall pyriform sinus cancer who received surgical treatment from January 2001 to December 2010 were retrospectively analyzed. Among them, 21 cases were given preoperative radiotherapy and surgery (R+ S). The radiation therapy dose was 45 Gy. And 14 cases' larynx is preserved. In addition, 27 cases were given postoperative radiotherapy and surgery (S+ R). The radiation therapy dose was 65 Gy. And 10 cases had preserved laryngeal function. Survival rates were analyzed by the Kaplan-Meier method. Chi-square test was used to compare complications between two groups. Results: The larynx preservation rate in R+ S group [66.7% (14/21)] was significantly higher than that in S+ R group [37.0% (10/27), P<0.05]. The complication rate and decannulation rate in R+ S group were 42.9% (9/21) and 64.3% (9/14), respectively, showing no difference compared with those in S+ R group [37.0% (10/27) and 50.0% (5/10), respectively] (all P>0.05). The complication rates of patients with and without larynx preservation were 41.7% (10/24) and 37.5% (9/24), respectively, showing no difference between two groups (P>0.05). The overall 3-years and 5-years survival rates for all patients were 54.2% (26/48) and 35.4% (17/48), respectively. There was no significant difference in survival rates between R+ S [38.1% (8/21)] group and S+ R group [33.3% (9/27), P>0.05)]. In the R+ S group, the survival rates in patients with and without larynx preservation were 40.0% (4/10) and 29.4% (5/17), respectively, showing no significant difference between two groups (P>0.05). Conclusions: It is secure and effective to choose the operation with laryngeal preservation for patient over 70 years of age with medial wall pyriform sinus cancer based on their physical conditions and the tumor extension. The preoperative- and postoperative-radiotherapy have the similar effect. Preoperative radiotherapy and surgery increases the laryngeal preservation rate.

Association of the expression levels in the skeletal muscle and a SNP in the CDC10 gene with growth-related traits in Japanese Black beef cattle.

Growth performance, as well as marbling, is the main breeding objective in Japanese Black (JB) cattle, the major beef breed in Japan. The septin 7 (CDC10) gene, involved in cellular proliferation, is located within a genomic region of a quantitative trait locus for growth-related traits. In this study, we first showed that the expression levels of the CDC10 gene in the skeletal muscle were higher in JB steers with extremely high growth performance than in JB steers with extremely low growth, using real-time PCR. Further, a single nucleotide polymorphism (SNP), NC_007302.5:g.63264949G>C, was detected in the promoter region of the CDC10 gene and genotyped in three Japanese cattle breeds (known as 'Wagyu' in Japan) and the Brown Swiss dairy cattle breed. All four cattle populations showed a moderate genetic diversity at the SNP of the CDC10 gene. An association analysis indicated that the SNP was associated with growth-related traits in JB cattle. These findings suggest possible effects of the expression levels in the skeletal muscle and the SNP of the CDC10 gene on growth-related traits in JB cattle. The CDC10 SNP may be useful for effective marker-assisted selection to increase beef productivity in JB beef cattle.

Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis.

Cathepsin B (CB), an important proteinase that participates in joint destruction in rheumatoid arthritis (RA), exhibits higher expression in fibroblast-like synoviocyte (FLS) of abnormal proliferative synovial tissues. Whether and how it affects the biological behaviours of RA-FLS, such as migration and invasion, are poorly understood. In the present study, CB expression in synovial tissues of patients with RA and ostearthritis (OA) were measured by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. Stable depletion of endogenous CB was achieved by small interfering RNA (siRNA) transfection, and decrease of CB activity was acquired by using its specific inhibitor (CA074Me). The effects of CA074Me and RNA interference (RNAi) treatments on proliferation, migration, invasion, matrix metalloproteinase (MMP)-2/-9 expression, focal adhesion kinase (FAK) activation, and mitogen-activated protein kinases (MAPKs) phosphorylation of FLS were analysed. In RA synovial tissues, CB was expressed at elevated levels compared with OA synovial tissues. CA074Me could inhibit invasion of FLS obtained from RA patients in an ex-vivo invasion model. CA074Me and siRNA treatments suppressed the migration and invasion of FLS, reduced the activity, expression and mRNA level of MMP-2, restrained the activation of FAK and reduced the expression of F-actin. Moreover, CA074Me decreased the phosphorylation of P38 MAPK and c-Jun N-terminal kinase (JNK) in FLS, while siCB treatment reduced the phosphorylation of P38 but not JNK. CB substantially contributes to the invasive phenotype of FLS that leads to joint destruction in RA. This proteinase may show promise as a therapeutic target in inflammatory arthritis.

Precision medicine approaches in obstructive sleep apnoea: The role of dentist-sleep physician partnerships.

Obstructive Sleep Apnoea (OSA) is a common heterogenous sleep disorder that is associated with a wide range of comorbidities and consequences, including the development of neurocognitive and cardiometabolic disorders. The heterogeneity of OSA necessitates a precision medicine approach to accurately diagnose this condition and to effectively manage patients. One of the primary models of precision medicine is described by the P4 approach of predicting those who are susceptible to disease, preventing the occurrence of disease, personalizing treatment, and encouraging patients to participate in their individual healthcare journey. Recent advances in oral appliance therapy and OSA monitoring techniques have fostered an exciting opportunity for enhanced collaboration between dentists and sleep physicians to optimize OSA precision medicine care. This review aims to discuss the sources of heterogeneity among OSA patients, provide an overview of the growing applications of oral appliance therapy and tailored monitoring programs for OSA that are shifting treatment to a more personalized and participatory model of care, and outline the pivotal role of dentists in managing patients with OSA.

Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Semen collection and polymerase chain reaction-based sex determination of black-headed and straw-necked ibis.

This study aimed to develop a polymerase chain reaction (PCR)-based sexing and effective semen collection methods for black-headed and straw-necked ibis species. However, most birds are not sexually dimorphic, that is, the sexes appear similar. Therefore, the gender should be determined before semen collection. DNA was extracted from the blood samples of 11 black-headed and 4 straw-necked ibis. The sex was determined after PCR amplification of the EE0.6 region of W-chromosome. The PCR products were separated using gel electrophoresis. A single band indicated the presence of the EE0.6 region and that the individual was a female, while no band indicated that the individual was a male. Further, the single bands from seven specimens were amplified. Semen collection was performed by massage or a combination of massage with electro-ejaculation and was attempted during all four seasons. The semen was successfully collected in March from male straw-necked ibis using the massage method. Limited motility, viability and concentration of straw-necked ibis sperm were observed. The sperm length was 180 µm and that of the nucleus was 30 µm with acrosome located at the tip of the nucleus. Thus, the PCR-based sexing proved to be an accurate molecular sexing method for black-headed and straw-necked ibis. Furthermore, we successfully collected semen and observed the stained sperm nucleus and acrosome of the straw-necked ibis sperm. We propose that the use of this PCR methodology can be applied as a routine method for sex determination and semen collection in ibis species for future ecological research. However, considering our limited success, further studies on semen collection method are required.

Association of variants in FABP4, FASN, SCD, SREBP1 and TCAP genes with intramuscular fat, carcass traits and body size in Chinese Qinchuan cattle.

This study aimed to genotype the variants in FABP4, FASN, SCD, SREBP1 and TCAP genes, and to analyze their associations with intramuscular fat (IMF) content, carcass traits and body size in Chinese Qinchuan cattle (QC). The association studies showed that the FABP4 c.220A > G polymorphism was significantly associated with ultrasound longissimus muscle depth (ULMD) and IMF, the FASN g.16024A > G polymorphism was significantly associated with ULMD and some body size traits, the SREBP1 84 bp indel was significantly associated with back fat thickness, ULMD and some body size traits. The frequencies of well-characterized A allele in FABP4 c.220A > G in Korean cattle (KOR) and Japanese Black cattle (JB), T allele in SCD g.8586C > T in KOR, SS genotype in SREBP1 84 bp indel in KOR and JB, DELDEL genotype in TCAP g.592-597CTGCAGinsdel in KOR were significantly higher than in Chinese cattle breeds. Thus, the associated four polymorphisms were expected to be genetic selection markers for meat quality, carcass traits and body size of QC.

[A prospective cohort study on BMI levels and risk of acute pancreatitis].

Objective: To investigate the effects of body mass index (BMI) levels at different baseline on the risk of new-onset acute pancreatitis (AP). Methods: The subjects were from the Kailuan Study Cohort and divided into 3 groups according to baseline BMI levels: BMI<24 kg/m2, normal weight; BMI 24-28 kg/m2, overweight; BMI≥28 kg/m2, obesity. The incidence of new-onset AP in these three groups was analyzed. The survival curve was plotted by Kaplan-Meier method, the cumulative incidence was calculated and tested by log-rank method. Multivariate Cox proportional hazards regression model was used to calculate HR of baseline BMI levels for AP. Results: A total of 123 841 subjects were included and followed up for (11.94±2.13) years, during which, 395 cases were found with AP. The incidence of AP was 2.67 per 10 000 person years in total population, and the incidences of AP were 2.20, 2.72 and 3.58 per 10 000 person-years in the normal, overweight and obesity groups, respectively. The cumulative incidences of AP was 0.32%, 0.40% and 0.49% in normal, overweight and obesity groups, respectively, which showed a significant inter-group difference by log-rank test (χ 2=13.17,P<0.01). The results of multivariable adjusted Cox proportional hazards regression model analysis indicated that obesity group (HR=1.45, 95%CI: 1.10-1.92) had a higher risk for AP compared with the normal BMI group. The subgroup analyses by age and sex showed that compared with the normal weight group,the HRs for AP in the obesity group was 1.58(95%CI:1.14-2.19) and 1.40(95%CI:1.03-1.90) among subjects younger than 60 years old and male subjects, respectively. After excluded onset AP within two years from baseline,with a control group from normal weight,the results of multivariate Cox proportional hazards regression model analysis indicated that the AP in the obesity group was 1.60 (95%CI: 1.18-2.15). Conclusion: Obesity may increase the risk of developing AP, particularly among young and middle-aged men.

[In vivo dynamic changes of inner ear guinea pigs with 9.4 T esla MRI].

Objective: To observe the imaging characteristics of guinea pig cochlear structure using 9.4 Tesla magnetic resonance imaging system at different time intervals of contrast agent distribution in the inner ear. Methods: Form May 2015 to October 2015, five albino guinea pigs were injected with Gd-DTPA via the right internal jugular vein (3 ml/kg). Inner ears were scanned with 9.4T MRI. At the 10 th, 30 th, 60 th, 90 th and 120 th minutes post-Gd-DTPA, we took inner ear images to detect changes of endolymph and perilymph. Using Image J software, we acquired MRI gray value through the first, second, third and apical turn of cochlear at different time points. Analysis by one-way ANOVA was taken to analyze the resultsusing GraphPad Prism 5 software. Results: Only outlines of the cochlea and vestibule were visible before Gd-DTPA injection and there was no clear distinction between endolymph and perilymph. Cochlea vestibule on T1 weighted images was enhanced at the 10 th (the first turn of cochlear 8 203±819) after injection, and then imaging of each part of cochlea, including cochlea, vestibule, semicircular canal and even endolymph and perilymph, can be distinguished clearly, because they enhanced gradually at the 30 th(10 489±819), 60 th(13 965±591), and at 90 th(18 050±1 250) after injection. While at the 120 th(18 952±1 185) minute, imaging was not significantly enhanced than at the 90 th minute. The speed and volume of contrast agent spreaded into the various parts of the inner ear were different, and changes with distribution of contrast agent in each part of the inner ear showed a rising process in a certain period of time. The distribution of contrast agent in the inner ear had concentration gradient via basal turn higher and apical turn lower. Conclusions: Endolymph of inner ear can be distinguished from the perilymph using a 9.4T MRI system with Gd-DTPA, and the best observation timer was 90 minutes after intravenous injection of contrast agent. In summary, our study provides the clearly visualized imaging evidence of the changes of the lymphatic fluid, which may be useful for diagnosis of inner ear diseases such as Meniere's Disease.

[Study on preparation of 3D printing degradable tissue engineering ossicles].

Objective: In combination with 3D printing technology and degradable composite materials, to discuss the preparation method of tissue engineering ossicles for middle ear hearing reconstruction. Methods: Domestic polymer (polylactic acid-glycolic acid copolymer, PLGA) and degradable ceramic material (ß-tricalcium phosphate, ß-TCP) were selected and prepared by low temperature deposition method according to the design ratio to Program according to the outline design code of the required scaffold to generate appropriate print files, and then the self-developed low-temperature deposition printing device was used to prepare tissue-engineered osseous scaffolds in accordance with the print files in a low-temperature environment. The scaffolds was freeze-dried and sterilized for later use after printing. Light microscopy and scanning electron microscopy were used to observe the apparent characteristics and internal structure of the scaffolds and to check its pore size, porosity and mechanical properties. Results: After printing, a degradable scaffold was obtained. Under the optical microscope, it was a small cylindrical shape with a diameter of 1.5 mm and a length of 6.0 mm, and its surface had micropores. The degradable scaffold had a horizontal and vertical interlaced warp and weft structure, the wire spacing was 1.2 mm, and the pores were connected to each other. The surface could see circular or quadrangular pores with a pore size of about 100-400 µm. The diameter of the inter-pore cross-linked channels was about 50 µm and the diameter of the surrounding circular micropores was about 10-40 µm. ß-TCP particles with a size of about 700 nm were attached to the surface of the PLGA material. The average porosity of the whole scaffolds was (83.43±0.01)%, and the content of BMP-2 loaded was about 0.7 µg/mm(3). After freeze-drying, the mechanical strength of the scaffold was moderate, and there was no obvious deformation during stretching and compression, which met the mechanical requirements of tissue engineering ossicles. Conclusions: Using the low-temperature deposition printing method and strictly controlled processes and conditions, a polymer-degradable ceramic ossicle tissue engineering scaffold can be prepared for implantation experiments. The scaffold has suitable porosity and mechanical properties, and can be loaded with osteoinductive factors.

Performance Evaluation Of Convolutions And Atrous Convolutions In Deep Networks For Retinal Disease Segmentation On Optical Coherence Tomography Volumes.

The deterioration of the retina center could be the main reason for vision loss. Older people usually ranging from 50 years and above are exposed to age-related macular degeneration (AMD) disease that strikes the retina. The lack of human expertise to interpret the complexity in diagnosing diseases leads to the importance of developing an accurate method to detect and localize the targeted infection. Approaching the performance of ophthalmologists is the consistent main challenge in retinal disease segmentation. Artificial intelligence techniques have shown enormous achievement in various tasks in computer vision. This paper depicts an automated end-to-end deep neural network for retinal disease segmentation on optical coherence tomography (OCT) scans. The work proposed in this study shows the performance difference between convolution operations and atrous convolution operations. Three deep semantic segmentation architectures, namely U-net, Segnet, and Deeplabv3+, have been considered to evaluate the performance of varying convolution operations. Empirical outcomes show a competitive performance to the human level, with an average dice score of 0.73 for retinal diseases.

[Relationship between waist circumference trajectory and new-onset non alcoholic fatty liver disease in the non-obese population].

Objective: To investigate the relationship between waist circumference trajectory and new-onset nonalcoholic fatty liver disease (NAFLD) in the non-obese population. Methods: The study cohort was composed of the ones who met the selection criteria in Kailuan study. Waist circumference trajectories of the participants in 2006-2007, 2008-2009 and 2010-2011 were determined by SAS Proc Traj program. Four groups with different waist circumference trajectories were generated, including low-, medium-, medium-high- and high-stability groups. All groups were followed up for their health conditions in 2012-2013, 2014-2015 and 2016-2017, respectively. Incidence rates of NAFLD during physical examination were compared among different waist circumference trajectory groups. Cox regression model was used to analyze the correlation between different waist circumference trajectory groups and new-onset NAFLD. Results: Finally, 12 477 observers were included in the statistical analysis, including 8 181 males and 4 296 females. There were 1 026 (8.2%), 5 183 (41.5%), 5 481 (44.0%) and 787 cases (6.3%) in the low, medium, medium-high and high stability-stability groups, respectively. There were 4 123 NAFLD cases occurred during the follow-up period. The cumulative incidence of NAFLD increased along with the increase of waist circumference trajectory (21%, 43%, 59%, 72%, respectively) (P<0.01). The risks of NAFLD were 2.411 (95%CI: 2.021-2.877), 4.050 (95%CI: 3.402-4.820) and 5.489 (95%CI: 4.506-6.686) times higher in medium-, medium-high- and high-stability group than that in the low-stability group (P<0.01). After adjusting for age, sex and other confounding factors, the risks of NAFLD in the medium-, medium-high- and high-stability groups were 2.150 (95%CI: 1.789-2.582), 3.176 (95%CI: 2.623-3.846) and 3.732 (95%CI: 2.987-4.662) times higher than that in the low-stability group. Conclusion: The risk of NAFLD in non-obese people increased along with the increase of waist circumference trajectory, which seemed to have played an independent risk factor for NAFLD.

Yuan-Hu Zhi Tong Prescription Mitigates Tau Pathology and Alleviates Memory Deficiency in the Preclinical Models of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by memory dysfunction, Aß plaques together with phosphorylated tau-associated neurofibrillary tangles. Unfortunately, the present existing drugs for AD only offer mild symptomatic cure and have more side effects. As such, developments of effective, nontoxic drugs are immediately required for AD therapy. Present study demonstrates a novel role of Chinese medicine prescription Yuan-Hu Zhi Tong (YZT) in treating AD, and it has substantiated the in vivo effectiveness of YZT in two different transgenic mice models of AD, namely P301S tau and 3XTg-AD mice. Oral treatment of YZT significantly ameliorates motor dysfunction as well as promotes the clearance of aggregated tau in P301S tau mice. YZT improves the cognitive function and reduces the insoluble tau aggregates in 3XTg-AD mice model. Furthermore, YZT decreases the insoluble AT8 positive neuron load in both P301S tau and 3XTg-AD mice. Using microarray and the "Connectivity Map" analysis, we determined the YZT-induced changes in expression of signaling molecules and revealed the potential mechanism of action of YZT. YZT might regulate ubiquitin proteasomal system for the degradation of tau aggregates. The research results show that YZT is a potential drug candidate for the therapy of tau pathogenesis and memory decline in AD.

Modulation of the sis gene transcript during endothelial cell differentiation in vitro.

Endothelial cells, which line the interior walls of blood vessels, proliferate at the site of blood vessel injury. Knowledge of the factors that control the proliferation of these cells would help elucidate the role of endothelial cells in wound healing, tumor growth, and arteriosclerosis. In vitro, endothelial cells organize into viable, three-dimensional tubular structures in environments that limit cell proliferation. The process of endothelial cell organization was found to result in decreased levels of the sis messenger RNA transcript and increased levels of the messenger RNA transcript for fibronectin. This situation was reversed on transition from the organized structure to a proliferative monolayer. These results suggest a reciprocity for two biological response modifiers involved in the regulation of endothelial cell proliferation and differentiation in vitro.

Different genetic and morphological outcomes for phages targeted by single or multiple CRISPR-Cas spacers.

CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against genetic invaders, such as bacteriophages. The systems integrate short sequences from the phage genome into the bacterial CRISPR array. These 'spacers' provide sequence-specific immunity but drive natural selection of evolved phage mutants that escape the CRISPR-Cas defence. Spacer acquisition occurs by either naive or primed adaptation. Naive adaptation typically results in the incorporation of a single spacer. By contrast, priming is a positive feedback loop that often results in acquisition of multiple spacers, which occurs when a pre-existing spacer matches the invading phage. We predicted that single and multiple spacers, representative of naive and primed adaptation, respectively, would cause differing outcomes after phage infection. We investigated the response of two phages, ϕTE and ϕM1, to the Pectobacterium atrosepticum type I-F CRISPR-Cas system and observed that escape from single spacers typically occurred via point mutations. Alternatively, phages escaped multiple spacers through deletions, which can occur in genes encoding structural proteins. Cryo-EM analysis of the ϕTE structure revealed shortened tails in escape mutants with tape measure protein deletions. We conclude that CRISPR-Cas systems can drive phage genetic diversity, altering morphology and fitness, through selective pressures arising from naive and primed acquisition events. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.