Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering in vivo production of α-branched polyesters.

Polymers are an important class of materials that are used for a broad range of applications, from drug delivery to packaging. Given their widespread use, a major challenge in this area is the development of technology for their production from renewable sources and efforts to promote their efficient recycling and biodegradation. In this regard, the synthesis of polyesters based on the natural polyhydroxyalkanoate (PHA) pathway offers an attractive route for producing sustainable polymers. However, monomer diversity in naturally-occurring polyesters can be limited with respect to the design of polymers with material properties suitable for various applications. In this work, we have engineered a pathway to produce α-methyl branched PHA. In the course of this work, we have also identified a PHA polymerase (CapPhaEC) from activated sludge from waste water treatment that demonstrates a higher capacity for incorporation of α-branched monomer units than those previously identified or engineered. Production in Escherichia coli allows the construction of microbial strains that produce the copolyesters with 21-36% branched monomers using glucose and propionate as carbon sources. These polymers have typical weight-average molar masses (Mw) ranging between 1.7-2.0 × 105 g mol-1 and display no observable melting transition, only relatively low glass transition temperatures from -13 to -20 °C. The lack of a melting transition indicates that these polymers are amorphous materials with no crystallinity, which is in contrast to the natural poly(hydroxybutyrate) homopolymer. Our results expand the utility of PHA-based pathways and provide biosynthetic access to α-branched polyesters to enrich the properties of bio-based sustainable polymers.
Interstitial Flow Recapitulates Gemcitabine Chemoresistance in A 3D Microfluidic Pancreatic Ductal Adenocarcinoma Model by Induction of Multidrug Resistance Proteins

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers due to a high chemoresistance and poor vascularization, which results in an ineffective systemic therapy. PDAC is characterized by a high intratumoral pressure, which is not captured by current 2D and 3D in vitro models. Here, we demonstrated a 3D microfluidic interstitial flow model to mimic the intratumoral pressure in PDAC. We found that subjecting the S2-028 PDAC cell line to interstitial flow inhibits the proliferation, while maintaining a high viability. We observed increased gemcitabine chemoresistance, with an almost nine-fold higher EC50 as compared to a monolayer culture (31 nM versus 277 nM), and an alleviated expression and function of the multidrug resistance protein (MRP) family. In conclusion, we developed a 3D cell culture modality for studying intratissue pressure and flow that exhibits more predictive capabilities than conventional 2D cell culture and is less time-consuming, and more scalable and accessible than animal models. This increase in microphysiological relevance might support improved efficiency in the drug development pipeline.
Salt Reduction Intervention in Families Investigating Metabolic, Behavioral and Health Effects of Targeted Intake Reductions: Study Protocol for a Four Months Three-Armed, Randomized, Controlled “Real-Life” Trial

Reductions in salt intake have the potential to markedly improve population health at low cost. Real life interventions that explore the feasibility and health effects of a gradual salt reduction lasting at least four weeks are required. The randomized controlled SalT Reduction InterVEntion (STRIVE) trial was developed to investigate the metabolic, behavioral and health effects of four months of consuming gradually salt reduced bread alone or in combination with dietary counselling. This paper describes the rationale and methods of STRIVE. Aiming at 120 healthy families, participants were recruited in February 2018 from the Danish Capital Region and randomly allocated into: (A) Salt reduced bread; (B) Salt reduced bread and dietary counseling; (C) Standard bread. Participants were examined before the intervention and at four months follow-up. Primary outcome is change in salt intake measured by 24 h urine. Secondary outcomes are change in urine measures of potassium and sodium/ potassium ratio, blood pressure, plasma lipids, the renin-angiotensin system, the sympathetic nervous response, dietary intake as well as salt taste sensitivity and preferences. The results will qualify mechanisms affected during a gradual reduction in salt intake in compliance with the current public health recommendations.
A New Cell Model for Investigating Prion Strain Selection and Adaptation

Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for strain selection and/or adaptation, but the underlying molecular mechanisms are unknown. Prion strains can be distinguished by their cell tropism in vivo and in vitro, which suggests that susceptibility to distinct prion strains is determined by cellular factors. The neuroblastoma cell line PK1 is refractory to the prion strain Me7, but highly susceptible to RML. We challenged a large number of clonal PK1 lines with Me7 and successfully selected highly Me7-susceptible subclones (PME) to investigate whether the prion strain repertoire of PK1 can be expanded. Notably, the Me7-infected PME clones were more protease-resistant when compared to RML-infected PME clones, which suggested that cell-adapted Me7 and RML are distinct prion strains. Strikingly, Me7-refractory cells, including PK1 and astrocytes in cortico-hippocampal cultures, are highly susceptible to prions, being derived from homogenates of Me7-infected PME cells, suggesting that the passage of Me7 in PME cells leads to an extended host range. Thus, PME clones represent a compelling cell model for strain selection and adaptation.
Bifunctionalized Silver Nanoparticles as Hg2+ Plasmonic Sensor in Water: Synthesis, Characterizations, and Ecosafety

In this work, hydrophilic silver nanoparticles (AgNPs), bifunctionalized with citrate (Cit) and L-cysteine (L-cys), were synthesized. The typical local surface plasmon resonance (LSPR) at λ max = 400 nm together with Dynamic Light Scattering (DLS) measurements (<2RH> = 8 ± 1 nm) and TEM studies (Ø = 5 ± 2 nm) confirmed the system nanodimension and the stability in water. Molecular and electronic structures of AgNPs were investigated by FTIR, SR-XPS, and NEXAFS techniques. We tested the system as plasmonic sensor in water with 16 different metal ions, finding sensitivity to Hg2+ in the range 1–10 ppm. After this first screening, the molecular and electronic structure of the AgNPs-Hg2+ conjugated system was deeply investigated by SR-XPS. Moreover, in view of AgNPs application as sensors in real water systems, environmental safety assessment (ecosafety) was performed by using standardized ecotoxicity bioassay as algal growth inhibition tests (OECD 201, ISO 10253:2006), coupled with determination of Ag+ release from the nanoparticles in fresh and marine aqueous exposure media, by means of ICP-MS. These latest studies confirmed low toxicity and low Ag+ release. Therefore, these ecosafe AgNPs demonstrate a great potential in selective detection of environmental Hg2+, which may attract a great interest for several biological research fields.
Miniature Switchable Millimeter-Wave BiCMOS Low-Noise Amplifier at 120/140 GHz Using an HBT Switch

A 120–140 GHz frequency-switchable, very compact low-noise amplifier (LNA) fabricated in a 0.13 µm SiGe:C BiCMOS technology is proposed. A single radio-frequency (RF) switch composed of three parallel hetero junction bipolar transistors (HBTs) in a common-collector configuration and a multimodal three-line microstrip structure in the input matching network are used to obtain a LNA chip of miniaturized size. A systematic design procedure is applied to obtain a perfectly balanced gain and noise figure in both frequency states (120 GHz and 140 GHz). The measured gain and noise figure are 14.2/14.2 dB and 8.2/8.2 dB at 120/140 GHz respectively, in very good agreement with circuit/electromagnetic co-simulations. The LNA chip and core areas are 0.197 mm2 and 0.091 mm2, respectively, which supposes an area reduction of 23.4% and 15.2% compared to other LNAs reported in this frequency band. The experimental results validate the design procedure and its analysis.
Evaluation of High-Resolution Mass Spectrometry for the Quantitative Analysis of Mycotoxins in Complex Feed Matrices

The selective and sensitive analysis of mycotoxins in highly complex feed matrices is a great challenge. In this study, the suitability of OrbitrapTM-based high-resolution mass spectrometry (HRMS) for routine mycotoxin analysis in complex feeds was demonstrated by the successful validation of a full MS/data-dependent MS/MS acquisition method for the quantitative determination of eight Fusarium mycotoxins in forage maize and maize silage according to the Commission Decision 2002/657/EC. The required resolving power for accurate mass assignments (<5 ppm) was determined as 35,000 full width at half maximum (FWHM) and 70,000 FWHM for forage maize and maize silage, respectively. The recovery (RA), intra-day precision (RSDr), and inter-day precision (RSDR) of measurements were in the range of 94 to 108%, 2 to 16%, and 2 to 12%, whereas the decision limit (CCα) and the detection capability (CCβ) varied from 11 to 88 µg/kg and 20 to 141 µg/kg, respectively. A set of naturally contaminated forage maize and maize silage samples collected in northern Germany in 2017 was analyzed to confirm the applicability of the HRMS method to real samples. At least four Fusarium mycotoxins were quantified in each sample, highlighting the frequent co-occurrence of mycotoxins in feed.
An IKK/NF-κB Activation/p53 Deletion Sequence Drives Liver Carcinogenesis and Tumor Differentiation

Background: Most liver tumors arise on the basis of chronic liver diseases that trigger inflammatory responses. Besides inflammation, subsequent defects in the p53-signaling pathway frequently occurs in liver cancer. In this study, we analyzed the consequences of inflammation and p53 loss in liver carcinogenesis. Methods: We used inducible liver-specific transgenic mouse strains to analyze the consequences of NF-κB/p65 activation mimicking chronic inflammation and subsequent p53 loss. Results: Ikk2ca driven NF-κB/p65 activation in mice results in liver fibrosis, the formation of ectopic lymphoid structures and carcinogenesis independent of p53 expression. Subsequent deletion of Trp53 led to an increased tumor formation, metastasis and a shift in tumor differentiation towards intrahepatic cholangiocarcinoma. In addition, loss of Trp53 in an inflammatory liver resulted in elevated chromosomal instability and indicated a distinct aberration pattern. Conclusions: In conclusion, activation of NF-κB/p65 mimicking chronic inflammation provokes the formation of liver carcinoma. Collateral disruption of Trp53 supports tumor progression and influences tumor differentiation and heterogeneity.
Suppressing Antibacterial Resistance: Chemical Binding of Monolayer Quaternary Ammonium Salts to Polymethyl Methacrylate in an Aqueous Solution and Its Clinical Efficacy

Antibacterial resistance (ABR) poses an enormous threat to human health. ABR mainly develops due to bacteria being constantly exposed to diluted levels of disinfectants. Here, we propose a method for suppressing ABR through the chemical binding of disinfectants to polymethyl methacrylate (PMMA) device surfaces in solutions of 5%, 10%, and 20% disinfectant concentrations. PMMA discs were fabricated from a commercial orthodontic acrylic resin system (Ortho-Jet) and quaternary ammonium salts (QAS), 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride (42% in methanol), were used as the disinfectant. The PMMA surfaces were activated in 3 M sulfuric acid at 80 °C for 5 h for the esterification of hydrolyzed QAS to PMMA. Fourier transform infrared difference spectra confirmed that the carboxy-terminated PMMA was chemically bound to the QAS. In vitro cell viability tests using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays revealed that 5%QAS-c-PMMA was more biocompatible than 10%QAS-c-PMMA and 20%QAS-c-PMMA. The results of antibacterial tests and clinical trials demonstrated the excellent antibacterial power of 5%QAS-c-PMMA. This method is the first solution-based approach to successfully avoid disinfectant leakage and subsequent ABR, as revealed by mass spectrometry studies of the solution obtained by agitating the disinfectant-bound PMMA for 28 days.
miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

Diabetic nephropathy (DN) is a common clinically relevant complication of diabetes that is associated with damage to the capillaries, yet the etiology of this condition remains unclear. Nuclear factor‐kappa B (NF‐κB) activation is known to be associated with DN‐related inflammation and disease progression. Recent work indicated that microRNAs are diagnostic biomarkers of DN progression associated with inﬂammation in the progression of DN. miR‐218 is known to play key regulatory roles in certain cancers in humans, while its influence on DN pathology remains uncertain. The present study, therefore, sought to assess how miR‐218 influences the progression of disease in both a rat streptozotocin‐induced model of DN and as well as an in vitro model system in which mouse podocytes were stimulated with high glucose levels. We found miR‐218 to be markedly downregulated in both model systems relative to appropriate controls, and this downregulation was associated with IKK‐β upregulation. In DN rat model, overexpressing miR‐218 was sufficient to reduce renal injury. We further determined that podocyte proliferation was markedly impaired by glucose treatment, leading to the apoptotic death of these cells, and miR‐218 mimics were able to reduce these phenotypes. Overexpressing miR‐218 also significantly dampened inflammatory responses in this model system, as evidenced by reduced tumor necrosis factor‐α, interleukin‐6 (IL‐6), IL‐1β, and MCP‐1 levels. We then confirmed that miR‐218 targeting the messenger RNA encoding IKK‐β using a dual‐luciferase reporter assay. Together, our results provide clear evidence that miR‐218 regulate NF‐κB‐mediated inflammation, which is central to DN progression.
The Mediating Effect of Workplace Spirituality on the Relation between Job Stress and Job Satisfaction of Cancer Survivors Returning to Work

This study aimed to investigate the mediating effect of workplace spirituality in the relation between job stress and job satisfaction as well as the level of job stress, job satisfaction, and workplace spirituality of cancer survivors returning to work. A total of 126 cancer survivors who returned to work more than six months prior to the research participated in this study. Participants were recruited through snowball sampling; they were visiting the outpatient clinic at two general hospitals located in a metropolitan city and their clinical stage was stage 0 or stage 1. The collected data were analyzed using SPSS 22.0. Job stress, workplace spirituality, and job satisfaction had a negative correlation, whereas workplace spirituality and job satisfaction had a positive correlation. The Sobel test was performed to verify the significance of the mediating effect size of workplace adaptation, the results confirmed a partial mediating effect of workplace spirituality on the relation between job stress and job satisfaction (Z = –4.72, p < 0.001). This study confirmed the mediating effect of workplace spirituality in the relation between job stress and job satisfaction. A systematic program needs to be developed to enhance workplace spirituality, a spiritual approach, to relieve job stress and increase job satisfaction.
Setting surface wipe limits for skin sensitizers

Guidance for managing potential dermal exposures has historically been qualitative in nature, for example, in the form of a DSEN notation. We propose a method that can provide quantitative guidance on how to establish and use surface wipe limits for skin sensitizers. The murine local lymph node assay (LLNA) is a validated test that not only identifies potential skin sensitizers but also provides an effective concentration (EC3) value. This provides quantitative dose–response information on induction of skin sensitization that permits estimates of sensitization thresholds and potency. Building upon the previously established correlation between LLNA EC3 values and human repeat insult patch testing no-effect levels, we present a quantitative method for setting surface wipe guidelines using the LLNA EC3. These limits can be used to assign compounds to occupational exposure bands and provide handling guidance for skin sensitizers of varying potency, supporting both exposure assessment and control strategies. A table is included that suggests a band of reasonable surface wipe limits (mg/100 cm2) for potentially all chemical sensitizers. When used in conjunction with a comprehensive industrial hygiene program that includes hazard communication, engineering controls, and personal protective equipment, skin exposure and consequent skin sensitization risks in the workplace can be minimized.
The role of C-reactive protein levels on the association of physical activity with lung function in adults

Objective Regular physical activity may be associated with improved lung function via reduced systemic inflammation, although studies exploring this mechanism are rare. We evaluated the role of C-reactive protein in blood, which is a common marker of systemic inflammation, on the association of physical activity with forced expiratory volume in one second and forced vital capacity. Methods Cross-sectional data on spirometry, C-reactive protein levels and self-reported physical activity (yes/no; ≥2 times and ≥1hr per week of vigorous physical activity) were available in the European Community Respiratory Health Survey (N = 2347 adults, 49.3% male, 28–56 years-old). A subsample was also assessed 10 years later using the International Physical Activity Questionnaire, and tertiles of Metabolic Equivalent of Task—minutes per week spent in vigorous, moderate and walking activities were calculated (N = 671, 49.6% male, 40–67 years-old). Adjusted cross-sectional mixed linear regression models and the “mediate” package in “R” were used to assess the presence of mediation. Results Despite positive significant associations between nearly all physical activity metrics with forced expiratory volume in one second and forced vital capacity, there was no evidence that C-reactive protein levels played a role. An influence of C-reactive protein levels was only apparent in the smaller subsample when comparing the medium to low tertiles of moderate activity (mean difference [95% CIs]: 21.1ml [5.2, 41.9] for forced expiratory volume in one second and 17.3ml [2.6, 38.0] for forced vital capacity). Conclusions In a population of adults, we found no consistent evidence that the association of physical activity with forced expiratory volume in one second or forced vital capacity is influenced by the level of C-reactive protein in blood.
Impact of exercise training program attendance and physical activity participation on six minute walk distance in patients with heart failure

ABSTRACT Background: Exercise training is recommended for all people with stable heart failure (HF) however adherence is poor. This study sought to describe exercise participation in recently hospitalized HF patients who participated in a 12-week exercise training program. The association between exercise training variables and improvement in 6-min walk distance (6MWD) was also investigated. Methods: This study is a secondary analysis of results from the intervention arm of the EJECTION-HF trial (ACTRN12608000263392), (n = 140). Exercise program attendance was defined according to session frequency (< 12 sessions vs ≥ 12 sessions) and attendance duration (< 6 weeks attendance vs ≥ 6 weeks) over the 12 weeks. Physical activity at baseline and follow up were reported according to self-report of 150 min of moderate intensity exercise per week. Primary outcome was change in 6MWD at 12 weeks. Results: Being physically active (OR 3.8, CI 1.3–11.5) and frequent program attendance (OR 2.7, CI 1.2–5.9) were associated with significant improvements in 6MWD. Program duration and baseline physical activity were not significantly associated with the outcome. Conclusions: Attainment of 150 min of moderate intensity exercise per week and at least weekly attendance at the program, were associated with significant improvements in 6MWD at follow up. Efforts should be made to assist patients with HF to achieve these targets.
Microfluidic-Based Approaches for Foodborne Pathogen Detection

Food safety is of obvious importance, but there are frequent problems caused by foodborne pathogens that threaten the safety and health of human beings worldwide. Although the most classic method for detecting bacteria is the plate counting method, it takes almost three to seven days to get the bacterial results for the detection. Additionally, there are many existing technologies for accurate determination of pathogens, such as polymerase chain reaction (PCR), enzyme linked immunosorbent assay (ELISA), or loop-mediated isothermal amplification (LAMP), but they are not suitable for timely and rapid on-site detection due to time-consuming pretreatment, complex operations and false positive results. Therefore, an urgent goal remains to determine how to quickly and effectively prevent and control the occurrence of foodborne diseases that are harmful to humans. As an alternative, microfluidic devices with miniaturization, portability and low cost have been introduced for pathogen detection. In particular, the use of microfluidic technologies is a promising direction of research for this purpose. Herein, this article systematically reviews the use of microfluidic technology for the rapid and sensitive detection of foodborne pathogens. First, microfluidic technology is introduced, including the basic concepts, background, and the pros and cons of different starting materials for specific applications. Next, the applications and problems of microfluidics for the detection of pathogens are discussed. The current status and different applications of microfluidic-based technologies to distinguish and identify foodborne pathogens are described in detail. Finally, future trends of microfluidics in food safety are discussed to provide the necessary foundation for future research efforts.
d-amino Acids in Health and Disease: A Focus on Cancer

d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.