Miracle-dz/UniFAR-FTUs huggingface dataset:
KLF11 (Krüppel-Like Factor 11) Inhibits Arterial Thrombosis via Suppression of Tissue Factor in the Vascular Wall

Objective— Mutations in Krüppel like factor-11 (KLF11), a gene also known as maturity-onset diabetes mellitus of the young type 7, contribute to the development of diabetes mellitus. KLF11 has anti-inflammatory effects in endothelial cells and beneficial effects on stroke. However, the function of KLF11 in the cardiovascular system is not fully unraveled. In this study, we investigated the role of KLF11 in vascular smooth muscle cell biology and arterial thrombosis. Approach and Results— Using a ferric chloride–induced thrombosis model, we found that the occlusion time was significantly reduced in conventional Klf11 knockout mice, whereas bone marrow transplantation could not rescue this phenotype, suggesting that vascular KLF11 is critical for inhibition of arterial thrombosis. We further demonstrated that vascular smooth muscle cell–specific Klf11 knockout mice also exhibited significantly reduced occlusion time. The expression of tissue factor (encoded by the F3 gene), a main initiator of the coagulation cascade, was increased in the artery of Klf11 knockout mice, as determined by real-time quantitative polymerase chain reaction and immunofluorescence. Furthermore, vascular smooth muscle cells isolated from Klf11 knockout mouse aortas showed increased tissue factor expression, which was rescued by KLF11 overexpression. In human aortic smooth muscle cells, small interfering RNA–mediated knockdown of KLF11 increased tissue factor expression. Consistent results were observed on adenovirus-mediated overexpression of KLF11. Mechanistically, KLF11 downregulates F3 at the transcriptional level as determined by reporter and chromatin immunoprecipitation assays. Conclusions— Our data demonstrate that KLF11 is a novel transcriptional suppressor of F3 in vascular smooth muscle cells, constituting a potential molecular target for inhibition of arterial thrombosis.
Aberrant hiPSCs-Derived from Human Keratinocytes Differentiates into 3D Retinal Organoids that Acquire Mature Photoreceptors

Human induced pluripotent stem cell (hiPSC)-derived three-dimensional retinal organoids are a new platform for studying the organoidogenesis. However, recurrent genomic aberration, acquired during generation of hiPSCs, limit its biomedical application and/or aberrant hiPSCs has not been evaluated for generation of differentiated derivatives, such as organoids and retinal pigment epithelium (RPE). In this study, we efficiently differentiated mosaic hiPSCs into retinal organoids containing mature photoreceptors. The feeder-free hiPSCs were generated from the human epidermal keratinocytes that were rapid in process with improved efficiency over several passages and maintained pluripotency. But, hiPSCs were cytogenetically mosaic with normal and abnormal karyotypes, while copy number variation analysis revealed the loss of chromosome 8q. Despite this abnormality, the stepwise differentiation of hiPSCs to form retinal organoids was autonomous and led to neuronal lamination. Furthermore, the use of a Notch inhibitor, DAPT, at an early timepoint from days 29–42 of culture improved the specification of the retinal neuron and the use of retinoic acid at days 70–120 led to the maturation of photoreceptors. hiPSC-derived retinal organoids acquired all subtypes of photoreceptors, such as RHODOPSIN, B-OPSIN and R/G-OPSIN. Additionally, the advanced maturation of photoreceptors was observed, revealing the development of specific sensory cilia and the formation of the outer-segment disc. This report is the first to show that hiPSCs with abnormal chromosomal content are permissive to the generation of three-dimensional retinal organoids.
Clathrate hydrates in interstellar environment

Significance Formation of clathrate hydrate (CH) requires high pressures and moderate temperatures, which enable their existence in marine sediments and the permafrost region of earth. The presence of CHs in interstellar medium (ISM) is still in question due to the extreme high vacuum and ultracold conditions present there. Here, we conclusively identified methane and carbon dioxide hydrates in conditions analogous to ISM. We found that molecular mobility and interactions play crucial roles in the formation of CHs, even though there is no external pressure to force cage formation. Various chemical processes on these hydrates in ISM may lead to relevant prebiotic molecules. Clathrate hydrates (CHs) are ubiquitous in earth under high-pressure conditions, but their existence in the interstellar medium (ISM) remains unknown. Here, we report experimental observations of the formation of methane and carbon dioxide hydrates in an environment analogous to ISM. Thermal treatment of solid methane and carbon dioxide–water mixture in ultrahigh vacuum of the order of 10−10 mbar for extended periods led to the formation of CHs at 30 and 10 K, respectively. High molecular mobility and H bonding play important roles in the entrapment of gases in the in situ formed 512 CH cages. This finding implies that CHs can exist in extreme low-pressure environments present in the ISM. These hydrates in ISM, subjected to various chemical processes, may act as sources for relevant prebiotic molecules.
The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection

Phagocytic cells capture and kill most invader microbes within the bactericidal phagosome, but some pathogens subvert killing by damaging the compartment and escaping to the cytosol. To prevent the leakage of pathogen virulence and host defence factors, as well as bacteria escape, host cells have to contain and repair the membrane damage, or finally eliminate the cytosolic bacteria. All eukaryotic cells engage various repair mechanisms to ensure plasma membrane integrity and proper compartmentalization of organelles, including the Endosomal Sorting Complex Required for Transport (ESCRT) and autophagy machineries. We show that during infection of Dictyostelium discoideum with Mycobacterium marinum, the ESCRT-I component Tsg101, the ESCRT-III protein Snf7/Chmp4/Vps32 and the AAA-ATPase Vps4 are recruited to sites of damage at the Mycobacterium-containing vacuole. Interestingly, damage separately recruits the ESCRT and the autophagy machineries. In addition, the recruitment of Vps32 and Vps4 to repair sterile membrane damage depends on Tsg101 but appears independent of Ca2+. Finally, in absence of Tsg101, M. marinum accesses prematurely the cytosol, where the autophagy machinery restricts its growth. We propose that ESCRT has an evolutionary conserved function to repair small membrane damage and to contain intracellular pathogens in intact compartments.
Qualitative analysis of the experiences of gay, bisexual and other men who have sex with men who use GetCheckedOnline.com: a comprehensive internet-based diagnostic service for HIV and other STIs

Objectives To describe the factors that influence gay, bisexual and other men who have sex with men’s (gbMSM) experiences with GetCheckedOnline.com (GCO) in British Columbia (BC), Canada. GCO clients complete an internet-based risk assessment and print a laboratory test requisition form for HIV and other STIs to take to a private laboratory for diagnostic services. Methods Drawing on a purposive stratified sampling framework, we conducted 37 in-depth semistructured interviews with gbMSM who had used GCO at least once between 2015 and 2017. Results Participants expressed a preference for GCO (instead of clinic-based testing) because of convenience, privacy and control over specimen collection (specifically with doing one’s own throat or anal swab). Participants preferred receiving their results online via GCO compared with phone or email follow-up by clinic staff. GCO was viewed positively because it offers gbMSM living outside of urban city centres easy access to diagnostic services, including access to pooled nucleic acid amplification testing. Many participants also continued to positively view the clinic-based services available for gbMSM in their community. These services were frequently described as highly competent, tailored and comprehensive in responding to more complex needs. For example, attending a clinic was viewed as preferential to GCO in instances where there was a desire to access services addressing co-occurring health issues (eg, mental health; substance use disorders). Almost all of the participants anticipated using both GCO and clinic-based services in the future. Conclusions gbMSM report positive experiences and perceptions of GCO; however, they do not view GCO as a panacea. The results of this study point to the need to ensure that a wide range of integrated service options (eg, online; clinic-based) are available to address the range of sexual health needs of gbMSM living in BC's diverse settings.
β6‐integrin serves as a novel serum tumor marker for colorectal carcinoma

Colorectal cancer (CRC) is one of the leading causes of cancer‐related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6‐integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro‐ and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non‐CRC control patients. A cut‐off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6‐levels were assessed in 26 CRC patients, pre‐ and post‐surgery, as well as during follow‐up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow‐up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.
Color Stability of CAD/CAM Ceramics Prepared with Different Surface Finishing Procedures.

PURPOSE To investigate the color stability of zirconia-reinforced lithium silicate glass-ceramic and lithium disilicate reinforced glass-ceramic, which were prepared with various surface finishing procedures, following 1-week, 2-week, 1-month, and 2-month storage in various beverages, and after the application of polishing paste. MATERIALS AND METHODS Lithium disilicate glass-ceramic (IPS e.max CAD HT) and zirconia-reinforced lithium silicate ceramic (Vita Suprinity HT) CAD/CAM blocks were sectioned with a diamond saw (Metkon) under water cooling into 1.5 × 7 × 12 mm dimensions (N = 120). All specimens were polished with silicon carbide paper (600-, 800-, and 1200-grit) under water for 120 seconds. The specimens were prepared using 3 surface finishing procedures: glaze, mechanical polishing, and external staining and glaze in accordance with manufacturers' instructions. Then, each group was divided into 2 storage subgroups, black tea and coffee (n = 10/group). Color values were measured in CIELAB color space with dental spectrophotometer (VITA Easyshade) at the initial stage, and following 1-week, 2-week, 1-month, 2-month storage, and after fine-grit polishing paste application (Proxyt). Color changes (ΔE) were calculated and statistically analyzed using ANOVA followed by Bonferroni corrected post-hoc tests using Number Cruncher Statistical System 2007 (α < 0.05). RESULTS For lithium disilicate glass-ceramic, glaze procedure showed statistically lower color change values than mechanical polishing and external staining and glaze surface finishing groups (p < 0.05) following storage in both beverages, whereas for zirconia-reinforced lithium silicate ceramic, glaze procedure showed statistically lower color change values than mechanical polishing, but statistically insignificant values with respect to external staining and glaze group, following storage in both beverages. Lithium disilicate glass-ceramic groups showed statistically lower or statistically insignificant color change values with respect to zirconia-reinforced lithium silicate ceramic groups, except for the external staining and glaze surface finishing group in coffee. Significantly lower discoloration values were obtained following polishing paste application, with respect to 2-month storage in beverages (p < 0.05). CONCLUSION Glazing alone led to more color stability with respect to mechanical polishing and external staining and glaze for zirconia-reinforced lithium silicate and lithium disilicate glass-ceramic. Lithium disilicate glass-ceramic showed higher color stability compared to zirconia-reinforced lithium silicate ceramic. Polishing paste resulted in a decrease in discoloration to clinically acceptable values.
Genetic effects of vascular endothelial growth factor and its receptor 2 on feather maturity in three chicken breeds

ABSTRACT 1. The goal of the current study was to evaluate the genetic effects of the vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2) on feather maturity in the Qingyuan partridge chicken, Guangxi sanhuang chicken and Princess chicken. 2. Both SSCP-PCR and qPCR were employed to detect the polymorphism and gene expression of the VEGF and VEGFR-2 genes. 3. Four SNPs were identified in the VEGFR-2 gene. Exon10-A69G was associated with feather maturity (P < 0.01). Princess chickens with the genotype EF had higher feather maturity scores (P < 0.01). Higher expression levels of VEGF and VEGFR-2 were detected in the immature feather group of Qingyuan partridge chickens, especially in the skin. 4. The VEGF and VEGFR-2 genes play critical roles in feather maturity. In addition, exon10-A69G and genotype EF in the Princess chicken could potentially be utilised as genetic markers to improve efficiency in breeding.
Serum Testosterone Level Within Normal Range Is Positively Associated with Nonalcoholic Fatty Liver Disease in Premenopausal but Not Postmenopausal Women.

BACKGROUND A positive relationship between testosterone level and nonalcoholic fatty liver disease (NAFLD) in women has been reported, but findings concerning the association are conflicting and inconclusive. MATERIALS AND METHODS We examined the association between testosterone level and the risk of NAFLD after stratification by menopausal status in 613 women (223 premenopausal women aged 21-52 years and 390 postmenopausal women aged 46-75 years). A diagnosis of fatty liver was based on abdominal ultrasonography. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD with 1 nmol/L increment in the log testosterone concentration were calculated after adjusting for confounding variables using multiple logistic regression analysis. RESULTS The prevalence of NAFLD was 19.2% among premenopausal women and 33.3% among postmenopausal women. After adjusting for age, regular exercise, type 2 diabetes, body mass index, mean arterial pressure, fasting plasma glucose, triglyceride, and high-density lipoprotein cholesterol, and testosterone levels, the OR (95% CI) for NAFLD was 2.79 (1.11-7.08) with 1 nmol/L increment of the log testosterone concentration in premenopausal women. However, these positive associations were not found in postmenopausal women after adjusting for the same covariables. CONCLUSION Serum testosterone level was positively associated with NAFLD in premenopausal women but not in postmenopausal women. Our findings suggest that higher androgenic activity may be at least partly involved in the pathogenesis of NAFLD, particularly in premenopausal women.
Longitudinal effects of maternal love withdrawal and guilt induction on Chinese American preschoolers’ bullying aggressive behavior

Abstract Bullying has been understudied among preschool children, especially those from Chinese American families. Previous research has also neglected the dimensional effects of psychological control on child bullying development. This study examined two psychological control dimensions, love withdrawal and guilt induction, and their effects on children's bullying aggressive behavior using a longitudinal design. Participants were first-generation Chinese American mothers (N = 133; mean age [Mage] = 37.82) and their preschool children (Mage = 4.48). Chinese immigrant mothers reported their psychologically controlling parenting and teachers rated children's bullying aggressive behaviors in the school setting. Confirmatory factor analyses were conducted to establish the psychometric properties and cross-wave measurement equivalence of the study constructs. Cross-lagged structural equation modeling analysis indicated that maternal love withdrawal prospectively predicted more bullying aggressive behavior, whereas guilt induction predicted less bullying aggressive behavior in children 6 months later. These results held after controlling for the initial level of children's problem behaviors and demographic variables (child age, gender, and maternal education). For child effects, child bullying aggressive behavior predicted more maternal guilt induction over time but not love withdrawal. Our findings highlight the importance of construct specificity and cultural context in understanding associations between parenting and child development.
Preclinical stress originates in the rat optic nerve head during development of autoimmune optic neuritis

Optic neuritis is a common manifestation of multiple sclerosis, an inflammatory demyelinating disease of the CNS. Although it is the presenting symptom in many cases, the initial events are currently unknown. However, in the earliest stages of autoimmune optic neuritis in rats, pathological changes are already apparent such as microglial activation and disturbances in myelin ultrastructure of the optic nerves. αB‐crystallin is a heat‐shock protein induced in cells undergoing cellular stress and has been reported to be up‐regulated in both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Therefore, we wished to investigate the timing and localization of its expression in autoimmune optic neuritis. Although loss of oligodendrocytes was not observed until the later disease stages accompanying immune cell infiltration and demyelination, an increase in oligodendrocyte αB‐crystallin was observed during the preclinical stages. This was most pronounced within the optic nerve head and was associated with areas of IgG deposition. Since treatment of isolated oligodendrocytes with sera from myelin oligodendrocyte glycoprotein (MOG)‐immunized animals induced an increase in αB‐crystallin expression, as did passive transfer of sera from MOG‐immunized animals to unimmunized recipients, we propose that the partially permeable blood–brain barrier of the optic nerve head may present an opportunity for blood‐borne components such as anti‐MOG antibodies to come into contact with oligodendrocytes as one of the earliest events in disease development.
Activation of liver X receptor suppresses osteopontin expression and ameliorates nephrolithiasis

Nephrolithiasis is a common disease of the urinary system, of which idiopathic calcium oxalate (CaOx) kidney stones, in particular, are one of the special types. In the initial stages of CaOx kidney stone formation, Randall's plaques (RPs) develop. Liver X receptors (LXRs) inhibit oxidative stress and inﬂammatory in other diseases; nevertheless, the role of LXRs in nephrolithiasis has yet to be elucidated. In this study, the role of LXRs in the progression of RP formation was investigated. Microarray analysis revealed that LXR/RXR levels were significantly greater in low‐plaque tissues (<5%) than in high‐plaque tissues (>5%), confirming the link between LXR activation and RP formation. Correspondingly, expression levels of two LXR target genes, LXRα and LXRβ, were lower in high‐plaque tissues than in low‐plaque tissues. In vitro, LXR agonist alleviated calcium oxalate monohydrate‐induced cellular calcium deposits and apoptosis. LXR activation decreased reactive oxygen species production and gene expression of inflammatory mediators, including osteopontin that has recently been demonstrated to correlate with the development of RPs. Moreover, p38 MAPK and JNK signaling may mediate LXR‐regulated expression in HK‐2 cells. In an animal model, the deposition was reduced by activating LXR, and osteopontin expression was also inhibited. Our findings suggest a role for LXRs in the progression of idiopathic CaOx kidney stones; LXR agonists may have therapeutic potential for the treatment of nephrolithiasis.
The Circadian Rhythm of Breakthrough Pain Episodes in Terminally-ill Cancer Patients

Opioid therapy must be adjusted to the rhythm of a cancer patient’s pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective longitudinal study was aimed at verifying the existence of a circadian rhythm of BTP episodes in terminally-ill cancer patients. Consecutive adult cancer patients at their EOL treated with long-acting major opioids to control background pain (Numeric Rating Scale ≤ 3/10) were recruited from two Italian palliative care services. Using a personal diary, patients recorded the frequency and onset of BTP episodes and the analgesic rescue therapy taken for each episode over a 7-day period. Rhythms identified in BTP episodes were validated by Cosinor analysis. Overall, 101 patients were enrolled; nine died during the study period. A total of 665 BTP episodes were recorded (average of 7.2 episodes, mean square error 0.8) per patient, with 80.6% of episodes recorded between 8:00 a.m. and 12:00 a.m. At Cosinor analysis, a circadian rhythm of BTP episodes was observed, with a Midline Estimating Statistics of the Rhythm (MESOR) of 1.5, a double amplitude of 1.8, and an acrophase at 12:30 p.m. (p < 0.001). Oral morphine was the most frequent analgesic rescue therapy employed. In terminally-ill cancer patients, BTP episodes follow a circadian rhythm; thus, tailoring the timing of opioid administration to this rhythm may prevent such episodes. This circadian rhythm of BTP episodes in terminally-ill cancer patients should be confirmed in larger samples.