In addition, through a sonothermal treatment in vivo, bone infection induced by multidrug-resistant Staphylococcus aureus (MRSA) is successfully eliminated in under 20 min of US without tissue damage. This work provides a new strategy for combating MRSA by strong sonothermal therapy through US interfacial engineering.A new mode of aromatic metamorphosis has been developed, which allows thiophenes and their benzo-fused derivatives to be converted to a variety of exotic heteroles. This transformation involves 1) the efficient generation of key 1,4-dianions by means of desulfurative dilithiation with lithium powder and 2) the subsequent trapping of the dianions with heteroatom electrophiles in a one-pot manner. Via the desulfurative dilithiation, the sulfur atoms of thiophenes are replaced also with a carbon-carbon double bond or a 1,2-phenylene for the construction of benzene rings.Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannaffective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Suggestions for disease severity grading and treatment goals are provided. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs. The treatment options discussed in this guideline are as follows acitretin, ciclosporin, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.

Single-sided

H-NMR is proposed for the estimation of morphological parameters of trabecular bone, and potentially the detection of pathophysiological alterations of bone structure. In this study, a new methodology was used to estimate such parameters without using an external reference signal, and to study intratrabecular and intertrabecular porosities, with a view to eventually scanning patients.

Animal trabecular bone samples were analyzed by a single-sided device. The Carr-Purcell-Meiboom-Gill sequence of

H nuclei of fluids, including marrow, confined inside the bone, was analyzed by quasi-continuous T

distributions and separated into two

H pools short and long T

components. The NMR parameters were estimated using models of trabecular bone structure, and compared with the corresponding micro-CT.

Without any further assumptions, the internal reference parameter (short T

signal intensity fraction) enabled prediction of the micro-CT parameters BV/TV (volume of the trabeculae/total sample volume) and BS/TV (external surface of the trabeculae/total sample volume) with linear correlation coefficient >0.80. The assignment of the two pools to intratrabecular and intertrabecular components yielded an estimate of average intratrabecular porosity (33±5)%. Using the proposed models, the NMR-estimated BV/TV and BS/TV were found to be linearly related to the corresponding micro-CT values with high correlation (>0.90 for BV/TV; >0.80 for BS/TV) and agreement coefficients.

Low-field, low-cost portable devices that rely on intrinsic magnetic field gradients and do not use ionizing radiation are viable tools for in vitro preclinical studies of pathophysiological structural alterations of trabecular bone.

Low-field, low-cost portable devices that rely on intrinsic magnetic field gradients and do not use ionizing radiation are viable tools for in vitro preclinical studies of pathophysiological structural alterations of trabecular bone.Normal mode analysis (NMA) is a fast and inexpensive approach that is largely used to gain insight into functional protein motions, and more recently to create conformations for further computational studies. However, when the protein structure is unknown, the use of computational models is necessary. Here, we analyze the capacity of NMA in internal coordinate space to predict protein motion, its intrinsic flexibility, and atomic displacements, using protein models instead of native structures, and the possibility to use it for model refinement. Our results show that NMA is quite insensitive to modeling errors, but that calculations are strictly reliable only for very accurate models. Our study also suggests that internal NMA is a more suitable tool for the improvement of structural models, and for integrating them with experimental data or in other computational techniques, such as protein docking or more refined molecular dynamics simulations.Encapsulated peritoneal sclerosis (EPS) is a rare, but frequently fatal, long-term complication of peritoneal dialysis. Endometriosis is a common gynecological problem but hemoperitoneum due to endometriosis has been reported to be extremely rare in hemodialysis (HD) patients. A 25-year-old female HD patient was admitted to our clinic with nausea, vomiting, abdominal pain, and weight loss for last 3 months. Candida tropicalis and Candida glabrata were isolated in the fungal cultures from peritoneal fluid. Her abdominal computerized tomography scan has shown irregular peritoneal calcifications, diffuse peritoneal thickening, dilatation of the small bowel loops, and cocoon formation which all were typical for EPS. Hemoperitoneum was reported to recur for four times with intervals suggesting menstrual cycles. Her peritoneal biopsy, along with the signs of EPS, has also revealed the presence of endometriosis. The patient died with symptoms of septic shock in the first year of EPS diagnosis.Rapid diagnosis is critical for the treatment and prevention of diseases. An advanced nanomaterial-based biosensing platform that detects COVID-19 antibodies within seconds is reported. The biosensing platform is created by 3D nanoprinting of three-dimensional electrodes, coating the electrodes by nanoflakes of reduced-graphene-oxide (rGO), and immobilizing specific viral antigens on the rGO nanoflakes. The electrode is then integrated with a microfluidic device and used in a standard electrochemical cell. When antibodies are introduced on the electrode surface, they selectively bind with the antigens, changing the impedance of the electrical circuit which is detected via impedance spectroscopy. Antibodies to SARS-CoV-2 spike S1 protein and its receptor-binding-domain (RBD) are detected at a limit-of-detection of 2.8 × 10-15 and 16.9 × 10-15 m, respectively, and read by a smartphone-based user interface. The sensor can be regenerated within a minute by introducing a low-pH chemistry that elutes the antibodies from the antigens, allowing successive sensing of test samples using the same sensor. Sensing of S1 and RBD antibodies is specific, which cross-reacts neither with other antibodies such as RBD, S1, and nucleocapsid antibody nor with proteins such as interleukin-6. The proposed sensing platform could also be useful to detect biomarkers for other infectious agents such as Ebola, HIV, and Zika.Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD) synthesis and is involved in cancer cell proliferation through regulation of energy production pathways. Therefore, NAMPT inhibitors are promising drugs for cancer therapy by limiting energy supply of tumours. Herein, we demonstrated that the NAMPT inhibitor FK866 ((E)-N-(4-(1-Benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) dose-dependently inhibited growth and cell motility of DU-145 prostate tumour spheroids and decreased the intracellular ATP concentration. The apoptosis marker cleaved caspase-3 remained unchanged, but the autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) was upregulated. Growth inhibition was reversed upon co-administration of NAD to the cell culture medium. FK866 decreased calcein as well as pheophorbide A efflux from tumour spheroids and increased doxorubicin toxicity, indicating interference with function of drug efflux transporters. DU-145 multicellular tumour spheroids expressed the stem cell associated markers CD133, CD44, Oct4, Nanog, Sox2, and drug transporters ABCB1, ABCG2, and ABCC1 which are associated with stem cell properties in cancer cells. The ABCB1 inhibitor zosuquidar, the ABCG2 inhibitor Ko143, and the ABCC1 inhibitor MK571 increased calcein retention. Neither protein expression of stem cell markers, nor drug transporters was significantly changed upon FK866 treatment. In conclusion, our data suggest that FK866 inhibits prostate cancer cell proliferation by interference with the energy metabolism, and function of drug efflux transporters.The regulatory circuitry underlying embryonic stem (ES) cell self-renewal is well defined, but how this circuitry is disintegrated to enable lineage specification is unclear. RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and preliminary data suggest that they might regulate ES cell fate. By combining bioinformatic analyses with functional screening, we identified seven RBPs played important roles for the exit from pluripotency of ES cells. We characterized hnRNPLL, which mainly functions as a global regulator of alternative splicing in ES cells. Specifically, hnRNPLL promotes multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation. hnRNPLL depletion thus leads to sustained expression of ES cell-preferred isoforms, resulting in a differentiation deficiency that causes developmental defects and growth impairment in hnRNPLL-KO mice. In particular, hnRNPLL-mediated alternative splicing of two transcription factors, Bptf and Tbx3, is important for pluripotency exit. These data uncover the critical role of RBPs in pluripotency exit and suggest the application of targeting RBPs in controlling ES cell fate.Pectus excavatum (PE) can be associated with cardiac disorders that also require surgical repair. Totally endoscopic robot-assisted mitral valve plasty for mitral valve regurgitation was performed while elevating the sternum with the aid of our original electrical sternum lifting system. Then, the Nuss procedure was performed successfully via small incision. Simultaneous robot-assisted cardiac surgery and the Nuss procedure is effective. Sternal elevation during cardiac surgery is very important for a safe procedure. The Nuss technique prevents perioperative cardiac compression and allows for correction of the pectus deformity with good cosmetic and functional results.