Exosomal miRNA 16-5p/29a-3p from pancreatic cancer induce adipose atrophy by inhibiting adipogenesis and promoting lipolysis.

Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia. MicroRNA sequencing of exosomal components from normal and cancer-derived exosomes revealed enrichment of miR-16-5p, miR-21-5p, miR-29a-3p, and miR-125b-5p in serum exosomes of mice harboring PDAC and patients with PDAC. Further, miR-16-5p and miR-29a-3p inhibited adipogenesis through decreasing Erlin2 and Cmpk1 expression which downregulates C/EBPβ and PPARγ. Synergistically, miR-29a-3p promotes lipolysis through increasing ATGL expression by suppressing MCT1 expression. Furthermore, PDAC-exosomes deprived of miR-16-5p and miR-29a-3p fail to induce fat loss. Hence, miR-16-5p and miR-29a-3p exosomal miRs are essential for PDAC-induced fat loss. Thus, we unravel that PDAC induces adipose atrophy via exosomal miRs. This knowledge may provide new diagnostic and therapeutic strategies for PDAC-induced cachexia

BigraphTalk: verified design of IoT applications

Graphical IoT device management platforms, such as IoTtalk, make it easy to describe interactions between IoT devices. Applications are defined by dragging-and-dropping devices and specifying how they are connected, e.g. a door sensor controlling a light. While this allows simple and rapid development, it remains possible to specify unwanted device configurations – such as using the same device to drive a motor up and down simultaneously, risking damaging the motor. We propose , a verification framework for IoTtalk that utilizes formal techniques, based on bigraphs, to statically guarantee that unwanted configurations do not arise. In particular, we check for invalid connections between devices, as well as type errors, e.g. passing a float to a boolean switch. To the best of our knowledge, is the first platform to support the graphical specification of correct-by-design IoT applications. provides fully automated verification and feedback without end-users ever needing to specify a bigraph. This means any application, specifiable in IoTtalk, is guaranteed, so long as verification succeeds, not to violate the given configuration constraints when deployed; with no extra cost to the user

Microstructure and superelastic properties of FeNiCoAlTi single crystals with the <100> orientation under tension

The microstructure and superelastic response of an Fe41 Ni28 Co17 Al11.5 Ti2.5 (at.%) single crystal along the [removed] orientation was investigated under tension at room temperature after aging at 600◦ C for 24 h. From the superelastic results, the samples aged at 600◦ C for 24 h exhibited 4.5% recoverable strain at room temperature. The digital image correlation (DIC) method was used to observe the strain distribution during the 6.5% applied strain loading. The DIC results showed that the strain was uniformly distributed during the loading and unloading cycles. Only one martensite variant was observed from the DIC results. This was related to the aging heat treatment times. The martensite morphology became a single variant with a longer aging time. The thermo-magnetization results indicated that the phase transformation and temperature hysteresis was around 36◦ C. Increasing the magnetic field from 0.05 to 7 Tesla, the transformation temperatures increased. The maximum magnetization was 160 emu/g under the magnetic field of 7 Tesla. From the transmission electron microscopy results, the L12 precipitates were around 10 nm in size, and they were high in Ni content and low in Fe content

One-pot synthesis of poly (3,4-ethylenedioxythiophene)-Pt nanoparticle composite and its application to electrochemical H2O2 sensor.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Poly(3,4-ethylenedioxythiophene)-Pt nanoparticle composite was synthesized in one-pot fashion using a photo-assisted chemical method, and its electrocatalytic properties toward hydrogen peroxide (H2O2) was investigated. Under UV irradiation, the rates of the oxidative polymerization of EDOT monomer along with the reduction of Pt4+ ions were accelerated. In addition, the morphology of PtNPs was also greatly influenced by the UV irradiation; the size of PtNPs was reduced under UV irradiation, which can be attributed to the faster nucleation rate. The immobilized PtNPs showed excellent electrocatalytic activities towards the electroreduction of hydrogen peroxide. The resultant amperometric sensor showed enhanced sensitivity for the detection of H2O2 as compared to that without PtNPs, i.e., only with a layer of PEDOT. Amperometric determination of H2O2 at -0.55 V gave a limit of detection of 1.6 μM (S / N = 3) and a sensitivity of 19.29 mA cm-2 M-1 up to 6 mM, with a response time (steady state, t95) of 30 to 40 s. Energy dispersive X-ray analysis, transmission electron microscopic image, cyclic voltammetry (CV), and scanning electron microscopic images were utilized to characterize the modified electrode. Sensing properties of the modified electrode were studied both by CV and amperometric analysis

Synthesis of Boron-Containing Primary Amines

[[abstract]]In this study, boron-containing primary amines were synthesized for use as building blocks in the study of peptoids. In the first step, Gabriel synthesis conditions were modified to enable the construction of seven different aminomethylphenyl boronate esters in good to excellent yields. These compounds were further utilized to build peptoid analogs via an Ugi four-component reaction (Ugi-4CR) under microwave irradiation. The prepared Ugi-4CR boronate esters were then successfully converted to the corresponding boronic acids. Finally, the peptoid structures were successfully modified by cross-coupling to aryl/heteroaryl chlorides via a palladium-mediated Suzuki coupling reaction to yield the corresponding derivatives in moderate to good yields.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙

Superior Mesenteric Artery Syndrome: A Single-institution Experience

Background:Superior mesenteric artery syndrome (SMAS) is a rare disease in adult. SMAS is characterized by acute, or, more commonly, chronic nonspecific symptoms due to duodenal obstruction and severe malnutrition with reduced arterio-mesenteric angle and distance. Surgical treatment may be necessary in most cases with chronic symptoms or when conservative treatment fails in SMAS.Methods:A retrospective chart review was performed on patients who underwent operation for SMAS from January 2008 to August 2020 in Cardinal Tien Hospital. Patients’ clinical presentations, surgical intervention, and outcomes.Results:Data from a total of 14 patients diagnosed with SMAS were analyzed, of which seven were diagnosed with SMAS by abdominal computed tomography and upper gastrointestinal series with water-soluble barium contrast. Six of the confirmed cases underwent surgery, namely, gastric decompression using a nasogastric tube, andcorrection of electrolyte imbalance. The nasoduodenal tube was placed through the obstructed duodenum to provide a high-nutrient fluid supplement. After conservative treatment failure, the patients underwent surgery. Of the six patients, four underwent duodenojejunostomy, one underwent a mini-laparotomy duodenojejunostomy bypass, and the last one underwent Roux-en-Y duodenojejunal bypass with duodenal feeding tube insertion.Conclusion:Patients with SMAS should initially be treated conservative. Surgical intervention should be considered in patients in whom conservative treatments were not effective.Complete resolution of all symptoms may not always be guaranteed after surgical intervention. Laparoscopy is currently widely used. In well-selected patients, minimally invasive or mini-laparotomy duodenojejunostomy is a safe and effective treatment for SMAS. The main advantages of mini-laparotomy duodenojejunostomy over other surgical approaches include half-length surgical incision and a shorter operative time. Duodenojejunostomy is rapidly becoming the standard procedure of this condition, and it has excellent outcomes comparable with those of open surgery

The Efficacy and Safety of a Fixed Combination of Chinese Herbal Medicine in Chronic Urticaria: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Background: Chronic urticaria is a bothersome skin disease, and Chinese herbal medicine (CHM) is commonly used as adjuvant therapy. This study aimed to evaluate the effectiveness and safety of the mixture of two CHM formula, Xiao-Feng-San (XFS) and Qing-Shang-Fang-Feng-Tang (QSFFT), in treating urticaria through a randomized, double-blind, placebo-controlled clinical trial.Methods: 78 participants entered the screening phase between November 2012 and August 2015. Participants were randomly and equally allocated in either CHM group (2 gm XFS and 2 gm QSFFT four times a day and 5 mg levocetirizine once daily for 28 days followed by 5 mg levocetirizine once daily alone for 28 days) or control group (placebo and 5 mg levocetirizine daily followed by 5 mg levocetirizine once daily for 28 days alone). Symptom improvement was set as the primary outcome, and the influence on sleep quality and changes in serum markers were used as secondary outcomes. Per protocol design was applied to the final analysis.Results: A total of 56 participants entered the final analysis stage. Participants in the CHM group had more prominent symptom relief on day 56 (the weekly urticaria activity score, UAS7, as 9.9 ± 9.2 vs. 15.6 ± 10.8, p = 0.038). In the CHM group, participants' symptom severity reduced progressively (trend analysis, p &lt; 0.001) while the decreasing trend was less favored in the control group (trend analysis, p = 0.056). The life quality improved gradually in both groups, while the differences between CHM and control groups were statistically insignificant. For urticaria-related cytokines, interferon-γ seemed to decrease positively in the CHM group (about 30.8% reduction from baseline, trend analysis p = 0.013). For safety issue, the CHM prescription was well-tolerated with no noticeable long-term side effects when compared to the control group. At 6-month follow-up of symptom changes after the end of the trial, the CHM group participants reported positive results in no recurrence or ≥50% improvement (36.3% in CHM group vs. 20% in Control group, p = 0.103).Conclusions: The combination of XFS and QSFFT tended to be feasible and tolerable adjuvant therapy for urticaria in addition to standard therapy. However, larger study population with longer follow-up duration may be still needed.Trial registration: NCT01715740 (ClinicalTrials.gov)

Growth and Characteristics of High-quality InN by Plasma- Assisted Molecular Beam Epitaxy

The high-quality InN epifilms and InN microdisks have been grown with InGaN buffer layers at low temperatures by plasma-assisted molecular beam epitaxy. The samples were analyzed using X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, and photoluminescence. The characteristics of the InN epifilms and InN microdisks were studied, and the role of InGaN buffer was evaluated

Hydroxyurea differentially modulates activator and repressors of γ-globin gene in erythroblasts of responsive and non-responsive patients with sickle cell disease in correlation with Index of Hydroxyurea Responsiveness

Hydroxyurea (HU), the first of two drugs approved by the US Food and Drug Administration for treating patients with sickle cell disease (SCD), produces anti-sickling effect by re-activating fetal γ-globin gene to enhance production of fetal hemoglobin. However, approximately 30% of the patients do not respond to HU therapy. The molecular basis of non-responsiveness to HU is not clearly understood. To address this question, we examined HU-induced changes in the RNA and protein levels of transcription factors NF-Y, GATA-1, -2, BCL11A, TR4, MYB and NF-E4 that assemble the γ-globin promoter complex and regulate transcription of γ-globin gene. In erythroblasts cultured from peripheral blood CD34+ cells of patients with SCD, we found that HU-induced changes in the protein but not the RNA levels of activator GATA-2 and repressors GATA-1, BCL11A and TR4 correlated with HU-induced changes in fetal hemoglobin (HbF) levels in the peripheral blood of HU high and low responders. However, HU did not significantly induce changes in the protein or RNA levels of activators NF-Y and NF-E4. Based on HU-induced changes in the protein levels of GATA-2, -1 and BCL11A, we calculated an Index of Hydroxyurea Responsiveness (IndexHU-3). Compared to the HU-induced fold changes in the individual transcription factor protein levels, the numerical values of IndexHU-3 statistically correlated best with the HU-induced peripheral blood HbF levels of the patients. Thus, IndexHU-3 can serve as an appropriate indicator for inherent HU responsiveness of patients with SCD

Highly reliable GIGA-sized synthetic human therapeutic antibody library construction

BackgroundMonoclonal antibodies (mAbs) and their derivatives are the fastest expanding category of pharmaceuticals. Efficient screening and generation of appropriate therapeutic human antibodies are important and urgent issues in the field of medicine. The successful in vitro biopanning method for antibody screening largely depends on the highly diverse, reliable and humanized CDR library. To rapidly obtain potent human antibodies, we designed and constructed a highly diverse synthetic human single-chain variable fragment (scFv) antibody library greater than a giga in size by phage display. Herein, the novel TIM-3-neutralizing antibodies with immunomodulatory functions derived from this library serve as an example to demonstrate the library’s potential for biomedical applications.MethodsThe library was designed with high stability scaffolds and six complementarity determining regions (CDRs) tailored to mimic human composition. The engineered antibody sequences were optimized for codon usage and subjected to synthesis. The six CDRs with variable length CDR-H3s were individually subjected to β-lactamase selection and then recombined for library construction. Five therapeutic target antigens were used for human antibody generation via phage library biopanning. TIM-3 antibody activity was verified by immunoactivity assays.ResultsWe have designed and constructed a highly diverse synthetic human scFv library named DSyn-1 (DCB Synthetic-1) containing 2.5 × 1010 phage clones. Three selected TIM-3-recognizing antibodies DCBT3-4, DCBT3-19, and DCBT3-22 showed significant inhibition activity by TIM-3 reporter assays at nanomolar ranges and binding affinities in sub-nanomolar ranges. Furthermore, clone DCBT3-22 was exceptionally superior with good physicochemical property and a purity of more than 98% without aggregation.ConclusionThe promising results illustrate not only the potential of the DSyn-1 library for biomedical research applications, but also the therapeutic potential of the three novel fully human TIM-3-neutralizing antibodies