Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivation, Aggregation and Conformational Changes of Polyphenol Oxidase from Quince (Cydonia oblonga Miller) Juice Subjected to Thermal and High-Pressure Carbon Dioxide Treatment

Polyphenol oxidase (PPO) causes the browning reaction in fruits and vegetables and deteriorates the quality. Thermal treatment for enzyme inactivation may result in defects as opposed to high pressure CO2 (HPCD) processing. In this study, the changes in activity, dissociation, aggregation and conformation of purified PPO from thermal and HPCD treated juice were investigated. HPCD exhibited inactivation of PPO at 55–65 °C whereas thermal processing alone at the same temperature resulted in PPO still showing activity. Under thermal treatment at 25 and 65 °C, the browning degree was higher (0.39 and 0.24) than for HPCD-treated juice (0.23 and 0.12). Fluorescence and circular dichroism spectral results indicated that HPCD induced large decreases in intensities, revealing a rearrangement of the secondary structure and destruction of the native configuration of the PPO molecule. The particle size distribution (PSD) pattern revealed structural modification leading to initial dissociation and subsequent aggregation of PPO after HPCD treatment. Polyacrylamide gel electrophoresis (PAGE) analysis exhibited that molecular size of protein was 40 kDa. In conclusion, the HPCD method was found to be more effective than thermal treatment to inactivate PPO. Structural modifications provided better insights into the phenomena of activation and inactivation of PPO.
The Epidemiology of Herpes Simplex Virus Type 1 in Asia: Systematic Review, Meta-analyses, and Meta-regressions

Abstract Background Herpes simplex virus type 1 (HSV-1) epidemiology in Asia was characterized by assessing seroprevalence levels and extent to which HSV-1 is isolated from clinically diagnosed genital ulcer disease (GUD) and genital herpes. Methods HSV-1 reports in Asia were systematically reviewed and synthesized, following PRISMA guidelines. Random-effects meta-analyses estimated pooled mean seroprevalence and proportion of HSV-1 detection in GUD and genital herpes. Random-effects meta-regressions identified predictors of seroprevalence and sources of between-study heterogeneity. Results Forty-nine relevant publications were identified. Fifty-four overall seroprevalence measures (182 stratified measures), and 8 and 24 proportions of HSV-1 detection in GUD and in genital herpes, respectively, were extracted. The pooled mean seroprevalence was 50.0% (n = 26; 95% confidence interval [CI], 41.3%–58.7%) for children and 76.5% (n = 151; 73.3%–79.6%) for adults. By age group, the pooled mean was lowest at 55.5% (n = 37; 95% CI, 47.5%–63.4%) in individuals aged <20 years, followed by 67.9% (n = 48; 62.4%–73.3%) in those aged 20–39 and 87.5% (n = 44; 83.4%–91.1%) in those aged ≥40 years. In meta-regression, age was the major predictor of seroprevalence. The mean proportion of HSV-1 detection was 5.6% (n = 8; 95% CI, 0.8%–13.6%) in GUD and 18.8% (n = 24; 12.0%–26.7%) in genital herpes. Conclusions HSV-1 epidemiology is transitioning in Asia. HSV-1 is probably playing a significant role as a sexually transmitted infection, explaining one-fifth of genital herpes cases. There is a need for expanded seroprevalence monitoring and GUD/genital herpes etiological surveillance.
Long-term relative survival from melanoma in Germany 1997–2013

Up-to-date melanoma relative survival (RS) estimates and trend analysis facilitate close monitoring of melanoma patients’ prognosis. This study aimed to provide recent 5-year and 10-year RS from melanoma, stratified by prognostic factors, and identify latest survival trends. Data from 12 German cancer registries were analysed. We included patients with primary cutaneous malignant melanoma (ICD-10: C43.X) diagnosed in 1997–2013 who were at least 15 years old. Five-year and 10-year RS were estimated by period analysis. For 10-year RS analyses, we excluded patients who were 75 years of age or older. Analyses were stratified by sex, age, histology, tumour stage, and body site. We included 82 901 patients, of whom 51% were women. The median age at diagnosis was 62 years. Five-year and 10-year RS in 2007–2013 were 92.4 and 90.8%, respectively. RS was higher in women. The prognosis worsened with older age and higher stage. In superficial spreading melanoma and lentigo maligna melanoma, RS was high; it was lower in nodular, acral lentiginous and ‘other’ melanoma. RS was the highest for melanoma on the arms; RS for melanoma on unknown or overlapping sites of the skin was the lowest. Five-year and 10-year RS increased significantly from 2005–2007 and 2008–2010 to 2011–2013, by 3.5 and 3.3 percentage points, respectively. For melanoma of ‘other’ histology, 5-year and 10-year RS increased significantly. Ten-year RS also increased significantly in men with superficial spreading melanoma and T4 melanoma, and in women with T3 melanoma. Melanoma RS improved, especially in certain subgroups. The reasons for improvements need to be investigated further.
Survivin as a potential therapeutic target of acetylsalicylic acid in pituitary adenomas

Acetylsalicylic acid (ASA) is known as a cancer preventing agent, but there is no data available regarding the effect of ASA on pituitary cells. We investigated 66 nonfunctioning (NFPA) and growth hormone (GH)-producing adenomas and 15 normal pituitary samples. Functional assays (cell viability, proliferation, flow cytometry cell cycle analysis, caspase-3 activation and DNA degradation) were applied to explore the effect of ASA, YM155 (survivin inhibitor), survivin-targeting siRNA and TNF-related apoptosis-inducing ligand (TRAIL) in RC-4B/C and GH3 cells. Pituitary adenoma xenografts were generated in immunocompromised mice. We found that survivin was overexpressed and TRAIL was downregulated in NFPAs compared to normal pituitary tissue. ASA decreased proliferation but did not induce apoptosis in pituitary cells. Additionally, ASA treatment decreased cells in S phase and increased cells in G2/M phase of the cell cycle. Inhibition of survivin using an inhibitor or siRNA-mediated silencing reversed the ASA-induced growth inhibition partially. In addition, we also found survivin-independent effects of ASA on the cell cycle that were mediated through inhibition of cyclin A, cyclin dependent kinase 2 (CDK2) and phospho-CDK2. We also aimed to test the effect of acetylsalicylic acid in an animal model using RC-4 B/C cells, but in contrast to GH3 cells, RC-4 B/C cells failed to adhere and grow a xenograft. We concluded that ASA inhibited the growth of pituitary adenoma cells. Survivin inhibition is a key mechanism explaining its antineoplastic effects. Our results suggest that inhibition of survivin with small molecules or ASA could serve as potential therapeutic agents in NFPA.
Causes of death in Japanese patients with atrial fibrillation: The Fushimi Atrial Fibrillation Registry

Aims To investigate the causes of death and the associated clinical factors in patients with atrial fibrillation (AF) in the contemporary clinical practice. Methods and results The Fushimi AF Registry is a community-based prospective survey of AF patients since March 2011 in Fushimi-ku, Kyoto. We investigated causes of death and the clinical indicators of cardiovascular (CV) and non-CV death in 4045 patients with available follow-up data by the end of November 2016. The mean age was 73.6 ± 10.9 years and the mean CHA2DS2-VASc score was 3.38 ± 1.69. Oral anticoagulants were prescribed in 55% of patients. During a median follow-up of 1105 days, there were 705 all-cause deaths (5.5%/year); 180 CV (26% of total deaths), 381 non-CV (54%), and 144 undetermined causes (20%). The most common causes of CV and non-CV death were heart failure (14.5%), malignancy (23.1%), and infection/sepsis (17.3%), while mortality due to stroke was only 6.5%. Mortality due to infection/sepsis and undetermined causes increased with aging. On multivariate analysis, the strongest indicator of CV death was pre-existing heart failure [hazard ratio (HR) 2.42, 95% confidence interval (CI) 1.66-3.54; P < 0.001] and that of non-CV death was anaemia (HR 2.84, 95% CI 2.22-3.65; P < 0.001). Conclusion In a Japanese community-based AF cohort, CV death was not mainly related to stroke but to heart failure. Non-CV death, mainly malignancy and infection, comprised more than a half of all deaths, which increased substantially in accordance with aging. Clinical factors that were associated with CV and non-CV death were distinct.
Detection of Hyperexcitability by Functional Magnetic Resonance Imaging after Experimental Traumatic Brain Injury.

Diagnosis of ongoing epileptogenesis and associated hyperexcitability after brain injury is a major challenge. Given that increased neuronal activity in the brain triggers a blood oxygenation level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI), we hypothesized that fMRI could be used to identify the brain area(s) with hyperexcitability during post-injury epileptogenesis. We applied fMRI to detect onset and spread of BOLD activation after pentylenetetrazol (PTZ)-induced seizures (PTZ, 30 mg/kg, intraperitoneally) in 16 adult male rats at 2 months after lateral fluid percussion (FPI)-induced traumatic brain injury (TBI). In sham-operated controls, onset of the PTZ-induced BOLD response was bilateral and first appeared in the cortex. After TBI, 5 of 9 (56%) rats exhibited ipsilateral perilesional cortical BOLD activation, followed by activation of the contralateral cortex. In 4 of 9 (44%) rats, onset of BOLD response was bilateral. Interestingly, latency from the PTZ injection to onset of the BOLD response increased in the following order: sham-operated controls (ipsilateral 132 ± 57 sec, contralateral 132 ± 57 sec; p > 0.05) < TBI with bilateral BOLD onset (ipsilateral 176 ± 54 sec, contralateral 178 ± 52 sec; p > 0.05) < TBI with ipsilateral BOLD onset (ipsilateral 406 ± 178 sec, contralateral 509 ± 140 sec; p < 0.05). Cortical lesion area did not differ between rats with ipsilateral versus bilateral BOLD onset (p > 0.05). In the group of rats with ipsilateral onset of PTZ-induced BOLD activation, none of the rats showed a robust bilateral thalamic BOLD response, only 1 of 5 rats had robust ipsilateral thalamic calcifications, and 4 of 5 rats had perilesional astrocytosis. These findings suggest the evolution of the epileptogenic zone in the perilesional cortex after TBI, which is sensitive to PTZ-induced hyperexcitability. Further studies are warranted to explore the evolution of thalamo-cortical pathology as a driver of epileptogenesis after lateral FPI.
Metabolic engineering of Escherichia coli for the enhanced production of l‐tyrosine

Despite wide applications of l‐tyrosine in the market, microbial overproduction of l‐tyrosine has been a great challenge due to the complex gene regulations involved in its biosynthetic pathway. To this end, effects of knocking out tyrR on the l‐tyrosine production were further explored during the strain development. Also, blocking cellular uptake of l‐tyrosine by knocking out tyrosine transporters was examined with respect to l‐tyrosine production. Using feedback‐resistant aroG and tyrA genes (aroGfbr and tyrAfbr hereafter) as initial overexpression targets, which encode 3‐deoxy‐7‐phosphoheptulonate synthase and chorismate mutase or prephenate dehydrogenase, respectively, various combinations of genes were subsequently overexpressed in the Escherichia coli wild‐type and tyrR knockout strain, and their effects on the l‐tyrosine production were examined. Co‐overexpression of aroGfbr, aroL and tyrC, a gene from Zymomonas mobilis functionally similar to tyrAfbr, but insensitive to l‐tyrosine, led to the greatest l‐tyrosine production regardless of the strains and plasmid constructs examined in this study. The strain BTY2.13 overexpressing the abovementioned three genes together with the removal of the l‐tyrosine‐specific transporter (tyrP) produced 43.14 g/L of l‐tyrosine by fed‐batch fermentation using the exponential feeding followed by DO‐stat feeding method. This outcome suggested that the tyrR gene knockout was not mandatory for the l‐tyrosine overproduction, but the production performance of strains having tyrR appeared to be highly affected by vector systems and feeding methods. With an optimal vector system and a feeding method, tyrP knockout appeared to be more effective in enhancing the l‐tyrosine than tyrR knockout.
Inhibition Effect of Three-Dimensional (3D) Nanostructures on the Corrosion Resistance of 1-Dodecanethiol Self-Assembled Monolayer on Copper in NaCl Solution

A novel and simple method to improve the corrosion resistance of copper by constructing a three-dimensional (3D) 1-dodecanethiol self-assembled monolayer (SAM) in 3.5% NaCl solution is reported in this study. Several drops of 1% H3PO4 solution are thinly and uniformly distributed on copper surface to form a 3D nanostructure constituted by Cu3(PO4)2 nanoflowers. The anticorrosion properties of 1-dodecanethiol SAM on copper surface and on copper surface that is treated with H3PO4 solution were evaluated. Results demonstrated that 1-dodecanethiol SAM on bare copper surface exhibits good protection capacity, whereas a copper surface that is pretreated with H3PO4 solution can substantially enhance the corrosion resistance of 1-dodecanethiol SAM.
Long-Term Trajectories of Posttraumatic Stress Disorder: Categorical versus Continuous Assessment

Objective: Long-term trajectories of posttraumatic stress disorder (PTSD) may fluctuate over time and typically conform to four heterogeneous patterns: resilience, recovery, delayed-onset, and chronic symptomatology. However, such fluctuations are typically short ranged and have rarely been investigated over the course of decades after the trauma. Moreover, existing studies have used a variety of measurements, either employing a categorical Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented approach or a continuous measure of symptom severity. The aim of this study was to evaluate the two methods of analyzing trajectories of PTSD by examining the level of concordance between them, their sensitivity, and their validity. Method: A total of 349 Israeli veterans from the 1973 Yom Kippur War were examined at four time points over more than four decades since the war. A latent class growth analysis (LCGA) was conducted to identify different PTSD trajectories, using both categorical and continuous PTSD assessments. Results: Descriptive results revealed that the four commonly observed patterns of PTSD are insufficient for capturing the range of individual PTSD trajectories. Using a categorical measure in the explorative LCGA yielded three trajectories (resilient, chronic, and delayed onset). The continuous measure yielded five trajectories (resilient, chronic, recovered, and two delayed-onset trajectories), which provided a slightly more nuanced distinction of participants’ distress-induced psychosocial dysfunction as compared to the three-trajectory solution. Conclusion: These findings suggest that using a continuous PTSD trajectory measure provides a somewhat more sensitive estimation of PTSD trajectories. More specifically, taking into consideration symptom intensity and fluctuation over time may provide a more comprehensive picture of the survivors’ distress.
Prostatic Carcinogenesis: More Insights

Background: Prostatic carcinoma ranks as the second most common malignant tumor and the fifth cause of cancer-related deaths in men. Many studies now focus on the different molecules involved in prostatic carcinogenesis. Maspin and prohibitin (PHB) are suggested to play crucial roles in the development and progression of many cancers; however, their roles in prostatic carcinogenesis have not been fully elucidated. Aim: This work was designed to study the immunohistochemical expression of maspin and PHB in prostatic carcinoma in comparison to their expression in benign prostatic hyperplasia (BPH) to give more insights about their roles in prostatic carcinogenesis. Materials and Methods: Archival blocks of 30 cases of prostatic adenocarcinomas and 15 cases of BPH were subjected to histopathological examination and immunohistochemical evaluation of maspin and PHB expression. Results: Maspin showed higher expression in prostatic carcinoma (88.9% of cases) compared to BPH (20% of cases). PHB expression was detected only in prostatic carcinoma (84.4% of cases), while all cases of BPH were negative. The expression of both maspin and PHB showed statistically significant increase with increasing Gleason score (P = 0.0125 and 0.0065 respectively). Conclusions: Overexpression of maspin and PHB in prostatic carcinoma reflects their vital roles in prostatic carcinogenesis. Their upregulation with increasing Gleason score indicates their prognostic significance. Moreover, PHB may differentiate between prostatic carcinoma and BPH being expressed only by malignant cells.
Non-specific effects of vaccinations in high-income settings: How to address the issue?

ABSTRACT “Non-specific effects” of vaccines go beyond the specific protective effects against the targeted diseases. They, if real, could theoretically be beneficial, neutral or negative. This article intends to answer the following questions: Do the non-specific effects of vaccines exist? Almost certainly yes, and they can be important in low-income countries Are non-specific effects also present in high-income countries? At least to some extent, it seems quite logical Can non-specific effects be systematically identified by the current systems of side effects/unintended reactions monitoring? Most likely not Could the Institute of Medicine proposals and some ongoing attempts solve the issue? It seems unlikely Could there be better, feasible and ethically acceptable ways to achieve the aforementioned objective? A proposal is presented about this issue, with the potential both to solve the problem with the most valid methods, and to overcome the ethical problems that have so far precluded the adoption of RCTs to study possible vaccine non-specific effects, monitored by long follow-up.
Characterization of the Chloroplast Genome Sequence of Acer miaotaiense: Comparative and Phylogenetic Analyses

Acer miaotaiense is an endangered species within the Aceraceae family, and has only a few small natural distributions in China’s Qingling Mountains and Bashan Mountains. Comparative analyses of the complete chloroplast genome could provide useful knowledge on the diversity and evolution of this species in different environments. In this study, we sequenced and compared the chloroplast genome of Acer miaotaiense from five ecological regions in the Qingling and Mashan Regions of China. The size of the chloroplast genome ranged from 156,260 bp to 156,204 bp, including two inverted repeat regions, a small single-copy region, and a large single-copy region. Across the whole chloroplast genome, there were 130 genes in total, and 92 of them were protein-coding genes. We observed four genes with non-synonymous mutations involving post-transcriptional modification (matK), photosynthesis (atpI), and self-replication (rps4 and rpl20). A total of 415 microsatellite loci were identified, and the dominant microsatellite types were composed of dinucleotide and trinucleotide motifs. The dominant repeat units were AT and AG, accounting for 37.92% and 31.16% of the total microsatellite loci, respectively. A phylogenetic analysis showed that samples with the same altitude (Xunyangba, Ningshan country, and Zhangliangmiao, Liuba country) had a strong bootstrap value (88%), while the remaining ones shared a similar longitude. These results provided clues about the importance of longitude/altitude for the genetic diversity of Acer miaotaiense. This information will be useful for the conservation and improved management of this endangered species.
PKC epsilon signaling effect on actin assembly is diminished in cardiomyocytes when challenged to additional work in a stiff microenvironment

The stiffness of the microenvironment surrounding a cell can result in cytoskeletal remodeling, leading to altered cell function and tissue macrostructure. In this study, we tuned the stiffness of the underlying substratum on which neonatal rat cardiomyocytes were grown in culture to mimic normal (10 kPa), pathological stiffness of fibrotic myocardium (100 kPa), and a nonphysiological extreme (glass). Cardiomyocytes were then challenged by beta adrenergic stimulation through isoproterenol treatment to investigate the response to acute work demand for cells grown on surfaces of varying stiffness. In particular, the PKCɛ signaling pathway and its role in actin assembly dynamics were examined. Significant changes in contractile metrics were seen on cardiomyocytes grown on different surfaces, but all cells responded to isoproterenol treatment, eventually reaching similar time to peak tension. In contrast, the assembly rate of actin was significantly higher on stiff surfaces, so that only cells grown on soft surfaces were able to respond to acute isoproterenol treatment. Förster Resonance Energy Transfer of immunofluorescence on the cytoskeletal fraction of cardiomyocytes confirmed that the molecular interaction of PKCɛ with the actin capping protein, CapZ, was very low on soft substrata but significantly increased with isoproterenol treatment, or on stiff substrata. Therefore, the stiffness of the culture surface chosen for in vitro experiments might mask the normal signaling and affect the ability to translate basic science more effectively into human therapy.
Zika virus outbreak in the Pacific: Vector competence of regional vectors

Background In 2013, Zika virus (ZIKV) emerged in French Polynesia and spread through the Pacific region between 2013 and 2017. Several potential Aedes mosquitoes may have contributed to the ZIKV transmission including Aedes aegypti, the main arbovirus vector in the region, and Aedes polynesiensis, vector of lymphatic filariasis and secondary vector of dengue virus. The aim of this study was to analyze the ability of these two Pacific vectors to transmit ZIKV at a regional scale, through the evaluation and comparison of the vector competence of wild Ae. aegypti and Ae. polynesiensis populations from different Pacific islands for a ZIKV strain which circulated in this region during the 2013–2017 outbreak. Methodology/principal findings Field Ae. aegypti (three populations) and Ae. polynesiensis (two populations) from the Pacific region were collected for this study. Female mosquitoes were orally exposed to ZIKV (107 TCID50/mL) isolated in the region in 2014. At 6, 9, 14 and 21 days post-infection, mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination, transmission rates and transmission efficiency, respectively. According to our results, ZIKV infection rates were heterogeneous between the Ae. aegypti populations, but the dissemination rates were moderate and more homogenous between these populations. For Ae. polynesiensis, infection rates were less heterogeneous between the two populations tested. The transmission rate and efficiency results revealed a low vector competence for ZIKV of the different Aedes vector populations under study. Conclusion/significance Our results indicated a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other factors especially the vector density, the mosquito lifespan or the large immunologically naive fraction of the population that may have contributed to the rapid spread of the ZIKV in the Pacific region during the 2013–2017 outbreak.