Muirburt6524

Tissue contractures are processes of cell-mediated contraction, irreversible in nature and typically associated with fibrotic phenomena. Contractures can be reproduced in vitro; here, we have used a medium-throughput model based on fibroblast-seeded fibrin (the 'contracture well'). Firstly, we show how profoundly these processes depend on the location of the contractile cells when on top of the material, fibroblasts produce an interfacial contracture (analog to capsular contraction around an implant), which tries and bends the construct; when seeded inside the material, they initiate a bulk contracture (analogue to a wound bed closure) that shrinks it from within. Secondly, we demonstrate that the interfacial and bulk contractures are also mechanically and biologically different processes. Thirdly, we show the potentially predictive value of this model, since it not only recapitulates the effect of pro-fibrotic factors (TGF-β1 for dermal (myo)fibroblasts), but can also indicate the fibrotic potential of a given cell population (here, dystrophic myoblasts more fibrotic than healthy or genetically corrected ones), which may have important implications in the identification of appropriate therapies.There is an urgent need for vascular scaffolds as a treatment option for cardiovascular diseases in the clinic. Here, we developed a simple and effective method to fabricate vascular scaffolds by direct 3D printing in air with gelatine (Gt) - alginate (Alg) - montmorillonite (MMT) nanocomposite bioinks. This work includes the optimization of key 3D printing parameters and the characterization of microscopic morphology, physicochemical properties, mechanical properties and preliminary biological properties. Successful 3D printing of linear and branched vascular scaffolds showed that the addition of nano-MMT improved the printability and shape accuracy. Scanning electron microscopy revealed that the inner and outer surfaces of the vascular scaffolds exhibited interconnected microporous structures favourable for nutrient delivery and cell infiltration. Axial and radial tensile tests indicated that the tensile strength and elastic modulus were similar to those of the native artery. The burst pressure of Gt-4%Alg-MMT was also in good accordance with the physiological pressure of natural blood vessels. In addition, a haemolysis test demonstrated that the haemolysis rate of Gt-4%Alg-MMT matched the gold standard of blood vessel substitution. A Live & Dead stain and a CCK-8 test confirmed the safe applicability of Gt-Alg-MMT as a biomaterial. Overall, the 3D-printed vascular scaffolds are promising candidates for in situ vascular tissue regeneration.Implant failure caused by unsatisfying osseointegration is still a noteworthy clinical problem. Strontium (Sr) has been confirmed to be a bioactive element that facilitates bone growth. In this study, Sr was surface incorporated in titanium (Ti) implant with different contents. The XRD results demonstrated that Sr existed mainly in the form of SrTiO3. All Sr-contained implants showed sustainable Sr2+ release behavior. Meanwhile, the Sr2+ release rate was proportional to the Sr content. The in vitro immersing test showed that the apatite-forming ability on the implant surface was decreased with the increase of Sr content. Conversely, the cell experiments manifested that implants with high content of Sr were more favorable to cell spreading, proliferation, osteogenic differentiation, and extracellular matrix mineralization. The in vivo implant experiment revealed that Sr-incorporation could improve osseointegration, new bone formation and mineralization, and bone-implant bonding strength. In addition, Ti5Sr, which possessed a combined good osteogenic activity and apatite-forming ability, exhibited the best in vivo overall performance. In summary, we first put forward the competitive effect of osteogenic activity and apatite-forming ability on bone-implant osseointegration, which would provide a new strategy for implant design.Exosomes are emerging in tissue engineering as up-and-coming acellular therapeutics, circumventing common restrictions inherent to cell-based therapies. The characteristics and function of exosomes are affected by the bidirectional communication of their original cells and the local microenvironment in which the cells reside (e.g., the stem cell niche). However, mesenchymal stem cells (MSCs) are customarily cultured in a traditional two-dimensional monolayer, with mechanical microenvironments varying substantially in physiological one. Few reports have addressed the effects of the 3D microenvironment on exosomal osteoinductivity. Herein, a 3D culture model is engineered through collagen hydrogel. Exosomes derived from three-dimensional culture (3D-Exos) and the conventional monolayer culture (2D-Exos) are collected and compared. The 3D culture resulted in high yield exosomes and greatly improved the efficiency of exosomes collection. The in vitro results demonstrated that the 3D-Exos induced significant promotions in osteogenic gene and protein expression (e.g., Runx2, OCN, OPN, COL1A1, and ALP), proliferation, and migration of Human bone marrow mesenchymal stem cells (hBMSCs) and inhibited hBMSCs apoptosis. Importantly, mechanistic studies revealed that the upregulation of the YAP signaling pathway is the underlying mechanism. Moreover, the 3D-Exos resulted in enhanced new bone formation and Runx2/OPN activation in rats with alveolar bone defects. These findings proposed a novel idea of the 3D culture strategy used to enhance the osteoinductivity of MSC-derived exosomes. This study also provided valuable references for exosome-based clinical applications for the treatment and regeneration of tissue defects from the perspective of culture dimensions.The development of biomimetic materials with anisotropic topological structure and wide range of adjustable mechanical properties is central to tissue engineering fields. In this work, on the basis of a stiff/stretchable dually crosslinked hydrogel, we paid more attention to the synergistic contribution of the confined drying and re-swelling (CDR) effect and Hofmeister effect to its micro structures, polymer aggregation states and mechanical strength. Specifically, by changing the pre-strains of the CDR procedure and the soaking time during the salting-out procedure, the arrangement structure orientation, chain-entanglement density, and supramolecular interaction strength within the polymer can be adjusted by changing the processing sequence of the two procedures, so that to obtain anisotropic biomimetic hydrogels with adjustable mechanical properties in a wide range. Thus, this engineered anisotropic polymer can mimic the natural tissues' mechanical properties in regeneration. Moreover and importantly, these anisotropic hydrogels exhibit prominent self-recovery properties. In summary, with the integration of molecular and structural engineering approaches, this study presents a universal strategy for developing anisotropic hydrogels, which could be widely used as biomimetic substitutes with anisotropic features in tissue regeneration.

The combination of targeted and systematic biopsies during MR/US-fusion prostate biopsy improves cancer detection over either modality alone.

To identify factors associated with disparity in detection of prostate cancer between systematic and targeted biopsies in magnetic resonance imaging positive zones.

We retrospectively analyzed 171 men receiving initial MR/US fusion biopsy at our institution from 2015 to 2018.

Disparity was defined as positive targeted but negative systematic biopsy within an magnetic resonance imaging-positive zone (PIRADS 3+), or vice versa. Multivariable logistic regression was used to identify factors associated with disparity in detection of cancer on a per lesion basis.

Three hundred and fifty-five lesions were targeted. For any cancer and clinically significant prostate cancer (csPCa), 37 (10%) and 24 (7%) lesions were target positive/systematic negative, respectively, while 30 (8%) and 23 (6%) lesions were target negative/systematic positive. In multivariable analysis, anterior location (OR 4.1, 95% CI 1.5-11.4, P = 0.007) was associated with csPCa target positive/systematic negative disparity, while higher prostate volume (OR 1.14, 95% CI 1.0-1.29, P = 0.04) was associated with csPCa target negative/systematic positive disparity. Shorter distance from apex (OR 1.02, 95% CI 1.01-1.04, P = 0.02) was associated with target positive/systematic negative disparity for any cancer. Limitations included relatively limited sample size and lack of prostatectomy specimen as a gold standard.

Anterior or apical lesion location favors better disease capture on targeted biopsies. When doing systematic-only biopsies, surgeons may consider sampling the anterior zone separately.

Anterior or apical lesion location favors better disease capture on targeted biopsies. When doing systematic-only biopsies, surgeons may consider sampling the anterior zone separately.

Most urologists use a 10-12 core template during transrectal ultrasound guided prostate biopsy (TRUS-B). A similar consensus template does not exist for transperineal prostate biopsy (TP-B) including the optimal number and location of biopsy cores. We examined our institutional cohort to develop an optimal systematic template for TP-B.

We prospectively monitored our first 200 consecutive free-hand TP-B. selleck kinase inhibitor These included men who were biopsy naïve (n = 117), had elevated PSA with prior negative biopsy (n = 18), and men on active surveillance (n = 65). All men underwent a 20 core TP-B with each core placed in a separate specimen container. This allowed the 20-core TP-B to be easily broken down as though fewer cores had been taken in each patient. Ten, 12, and 16 core templates were designed a priori and compared within each patient to the 20 core template. The highest Grade Group (GG) at pathologic analysis was assigned to each biopsy. Primary outcome was detection of clinically significant prostate cancer, detematic biopsy template for men undergoing TP-B.PII proteins are multitasking information-processing proteins occurring in bacteria, archaea, and plastids, decoding the metabolic state of the cells and providing this information to various regulatory targets. Research in recent years identified a wide range of novel PII targets mainly through ligand fishing assays, indicating that PII proteins evolved into major regulatory hubs of cellular metabolism. PII proteins orchestrate not only key steps of nitrogen and carbon metabolism but rather control a wide range of transporters and can also regulate the production of signaling molecules (c-di-GMP) and cofactors (NAD+). A recently identified class of PII-interacting proteins, which by themselves have no enzymatic activity, modulate cellular processes through protein interactions, further extending the regulatory range of PII proteins.

An outbreak of SARS-CoV-2 Delta variant infection occurred in Pingtung, Taiwan, in June 2021. In this study, we aimed to elucidate the clinical characteristics of the Delta-variant SARS-CoV-2 infection and the treatment outcome of antiviral agents in patients from Pingtung County in Southern Taiwan.

A total of 11 patients with Delta-variant COVID-19 were consecutively admitted to a governmental hospital in June 2021. Baseline characteristics and treatment outcome were evaluated.

All patients were symptomatic. The most common symptoms were cough (72.7%), followed by fever (54.5%), headache (18.2%) and dysosmia/dysgeusia (18.2%). Two patients developed pneumonia without mechanical ventilation requirement. Compared to patients without pneumonia, those with pneumonia had higher aspartate aminotransferase (AST) (21.0 vs. 126.0 IU/L, P=0.03) and lactate dehydrogenase (LDH) (143.1 vs. 409.0 IU/mL, P=0.03), and ferritin (0.2 vs. 2.0mg/L, P=0.046) levels. Pneumonia improved after 2-week treatment, and no mortality occurred after 30 days of diagnosis.