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The trap stiffness us the key property in using optical tweezers as a force transducer. Force reconstruction via maximum-likelihood-estimator analysis (FORMA) determines the optical trap stiffness based on estimation of the particle velocity from statistical trajectories. Using a modification of this technique, we determine the trap stiffness for a two micron particle within 2 ms to a precision of ∼10% using camera measurements at 10 kfps with the contribution of pixel noise to the signal being larger the level Brownian motion. This is done by observing a particle fall into an optical trap once at a high stiffness. This type of calibration is attractive, as it avoids the use of a nanopositioning stage, which makes it ideal for systems of large numbers of particles, e.g., micro-fluidics or active matter systems.CX3C Motif Chemokine Ligand 1 (CX3CL1; fractalkine) has been implicated in the pathogenesis of rheumatoid arthritis (RA) and its inhibition was found to attenuate arthritis in mice as well as in a clinical trial. BMS303141 Therefore, we investigated the effects of an anti-CX3CL1 monoclonal antibody (mAb) on immune-mediated interstitial lung disease (ILD) in SKG mice, which exhibit similar pathological and clinical features to human RA-ILD. CX3CL1 and CX3C chemokine receptor 1 (CX3CR1), the receptor for CX3CL1, were both expressed in the fibroblastic foci of lung tissue and the number of bronchoalveolar fluid (BALF) cells was elevated in ILD in SKG mice. No significant changes were observed in lung fibrosis or the number of BALF cells by the treatment with anti-CX3CL1 mAb. However, significantly greater reductions were observed in the number of M1 macrophages than in M2 macrophages in the BALF of treated mice. Furthermore, CX3CR1 expression levels were significantly higher in M1 macrophages than in M2 macrophages. These results suggest the stronger inhibitory effects of the anti-CX3CL1 mAb treatment against the alveolar infiltration of M1 macrophages than M2 macrophages in ILD in SKG mice. Thus, the CX3CL1-CX3CR1 axis may be involved in the infiltration of inflammatory M1 macrophages in RA-ILD.Among Citrus species, lemon is one of the most susceptible to mal secco disease, a tracheomycosis caused by the mitosporic fungus Plenodomus tracheiphilus, which induces chlorosis followed by leaf drop and progressive desiccation of twigs and branches. Severe infection can cause the death of the plant. Since no effective control strategies are available to efficiently control the pathogen spread, host tolerance is the most desirable goal in the struggle against mal secco disease. To date, both traditional breeding programs and biotechnological techniques were not efficient in developing novel varieties coupling tolerance to mal secco with optimal fruit quality. Furthermore, the genetic basis of host resistance has not been fully deciphered yet, hampering the set-up of marker-assisted selection (MAS) schemes. This paper provides an overview of the biotechnological approaches adopted so far for the selection of mal secco tolerant lemon varieties and emphasizes the promising contribution of marker-trait association analysis techniques for both unraveling the genetic determinism of the resistance to mal secco and detecting molecular markers that can be readily used for MAS. Such an approach has already proved its efficiency in several crops and could represent a valuable tool to select novel lemon varieties coupling superior fruit quality traits and resistance to mal secco.In this study, we developed a radial artery pulse acquisition system based on finger-worn dense pressure sensor arrays to enable three-dimensional pulse signals acquisition. The finger-worn dense pressure-sensor arrays were fabricated by packaging 18 ultra-small MEMS pressure sensors (0.4 mm × 0.4 mm × 0.2 mm each) with a pitch of 0.65 mm on flexible printed circuit boards. Pulse signals are measured and recorded simultaneously when traditional Chinese medicine practitioners wear the arrays on the fingers while palpating the radial pulse. Given that the pitches are much smaller than the diameter of the human radial artery, three-dimensional pulse envelope images can be measured with the system, as can the width and the dynamic width of the pulse signals. Furthermore, the array has an effective span of 11.6 mm-3-5 times the diameter of the radial artery-which enables easy and accurate positioning of the sensor array on the radial artery. This study also outlines proposed methods for measuring the pulse width and dynamic pulse width. The dynamic pulse widths of three volunteers were measured, and the dynamic pulse width measurements were consistent with those obtained by color Doppler ultrasound. The pulse wave velocity can also be measured with the system by measuring the pulse transit time between the pulse signals at the brachial and radial arteries using the finger-worn sensor arrays.Recent work has shown that bilirubin has a hormonal function by binding to the peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that drives the transcription of genes to control adiposity. Our previous in silico work predicted three potential amino acids that bilirubin may interact with by hydrogen bonding in the PPARα ligand-binding domain (LBD), which could be responsible for the ligand-induced function. To further reveal the amino acids that bilirubin interacts with in the PPARα LBD, we harnessed bilirubin's known fluorescent properties when bound to proteins such as albumin. Our work here revealed that bilirubin interacts with threonine 283 (T283) and alanine 333 (A333) for ligand binding. Mutational analysis of T283 and A333 showed significantly reduced bilirubin binding, reductions of 11.4% and 17.0%, respectively. Fenofibrate competitive binding studies for the PPARα LBD showed that bilirubin and fenofibrate possibly interact with different amino acid residues. Furthermore, bilirubin showed no interaction with PPARγ. This is the first study to reveal the amino acids responsible for bilirubin binding in the ligand-binding pocket of PPARα. Our work offers new insight into the mechanistic actions of a well-known molecule, bilirubin, and new fronts into its mechanisms.Resveratrol can affect the physiology or biochemistry of offspring in the maternal-fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4-8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p less then 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut-liver axis in the offspring.Immune-checkpoint inhibitors (ICIs) have widened the therapeutic scenario of different cancer types. Phase I/II trials have been designed to evaluate the role of ICIs both as single agents and in combination in neuroendocrine neoplasms (NENs), but as yet no randomized controlled phase III trials have been carried out. A systematic review and meta-analysis of studies published could help to reduce the biases of single-phase II trials. Efficacy data were obtained on 636 patients. Pooled percentages of the overall response rate (ORR) and disease control rate (DCR) were 10% (95% CI 6-15%, I2 = 67%, p less then 0.1) and 42% (95% CI 28-56%, I2 = 93%, p less then 0.1), respectively. Median progression-free survival (mPFS) was 4.1 months (95% CI 2.6-5.4; I2 = 96%, p less then 0.1) and median overall survival (mOS) was 11 months (95% CI 4.8-21.1; I2 = 98%, p less then 0.1). Among the ICIs used as single agents, the anti-PD1 toripalimab achieved the highest ORR. Combination regimens were superior to monotherapy, e.g., the ICI combination nivolumab + ipilimumab, and the ICI + anti-angiogenetic combination atezolizumab + bevacizumab, both of which warrant further investigation. Promising efficacy and a good safety profile of ICIs represent a valid opportunity for expanding the therapeutic landscape of NENs. Predictive biomarkers are needed to identify the most suitable candidates for these regimens.The prevalence of overweight/obesity in the adult population in the Philippines has doubled in the past 20 years. Zumba exercise has recently been implemented throughout the Philippines. However, there is scarce information on the effects of Zumba on obesity and Zumba participants' characteristics in the Philippines. This study described the current practice of Zumba in the Philippines, along with the practitioners' characteristics, and identified factors associated with Zumba participation. In this observational, cross-sectional study, a structured questionnaire was used to survey 10 Zumba locations in September 2019. Anthropometric measurements of participants were assessed. Respondents included 171 women (88.6%) and 22 men (11.4%), with a mean (±standard deviation [SD]) age of 44.1 (±8.9) years. All respondents answered that Zumba was enjoyable, and some answered "very enjoyable". Determinants of frequent participation were as follows being older than the mean age of participants, starting Zumba to enjoy dancing, starting Zumba not to lose weight, shopping mall location, and participation fee required. "To enjoy dance" being a motivation for Zumba practice was identified as a determinant of frequent participation rather than "to lose weight." The element of "enjoyable" may strongly influence the continuation and frequent participation of Zumba exercise in the Philippines.The potential of tannic acid (TA) as a dispersing agent for graphene (G) in aqueous solutions and its interaction with riboflavin have been studied under different experimental conditions. TA induces quenching of riboflavin fluorescence, and the effect is stronger with increasing TA concentration, due to π-π interactions through the aromatic rings, and hydrogen bonding interactions between the hydroxyl moieties of both compounds. The influence of TA concentration, the pH, and the G/TA weight ratio on the quenching magnitude, have been studied. At a pH of 4.1, G dispersed in TA hardly influences the riboflavin fluorescence, while at a pH of 7.1, the nanomaterial interacts with riboflavin, causing an additional quenching to that produced by TA. When TA concentration is kept constant, quenching of G on riboflavin fluorescence depends on both the G/TA weight ratio and the TA concentration. The fluorescence attenuation is stronger for dispersions with the lowest G/TA ratios, since TA is the main contributor to the quenching effect.
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