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This molecular tool can potentially replace its genetic and viral forms in the cardiac reprogramming of fibroblasts to induce a cardiac transcriptional profile in an integration-free manner and elucidating its role in various biological processes and diseases. KEY POINTS • Screening of the suitable gene construct was performed and identified. • Screening of optimal expression conditions was performed and identified. • Native purification of recombinant human MESP1 protein from E. coli was performed. • Recombinant MESP1 protein has retained its secondary structure after purification.Nitrate leaching is severe in greenhouse where excessive nitrogen is often applied to maintain high crop productivities. In this study, we investigated the effects of carbon amendment in the subsoil on nitrate leaching and the emission of greenhouse gases (CH4 and N2O) using a soil column experiment. Carbon amendment resulted in over 39% reduction in nitrate leaching and 25.3% to 60.6% increase of total N content in the subsoil zone as compared to non-amended control. Strikingly, the abundance of nirS, nosZ, and 16S rRNA were higher in the treatment than the corresponding controls while no significant effect was detected for nirK. Carbon amendment explained 14%, 10%, and 4% of the variation in the community of nosZ, nirS, and nirK, respectively. It also considerably (more than 7 times) enriched genera such as Anaerovorax, Pseudobacteroides, Magnetospirillum, Prolixibacter, Sporobacter, Ignavibacterium, Syntrophobacter, Oxobacter, Hydrogenispora, Desulfosporomusa, Mangrovibacterium, and Sporomusa, as revealed by the analysis of 16S rRNA amplicon. Network analysis further uncovered that carbon amendment enriched three microbial hubs which mainly consists of positively correlated nirS, nosZ, and anaerobic bacterial populations. In summary, carbon amendment in the subsoil mitigated nitrate leaching and increased the nitrogen pool by possible activation of denitrifying and anaerobic bacterial populations. KEY POINTS • Carbon amendment in subsoil reduced NO3- leaching by over 39% under high N input. • Carbon amendment increased the total N in subsoil from 25.3% to 60.6%. check details • Carbon amendment enriched nirS- and nosZ-type denitrifying bacteria in subsoil.Many soft tissue masses have an indeterminate appearance on MRI, often displaying varying degrees and extent of T2 hyperintensity. However, a subset of neoplasms and tumor-like lesions may exhibit prominent areas of T2 hypointensity relative to skeletal muscle. The hypointensity observed on T2-weighted MRI can be caused by a variety of substances, including evolving blood products, calcifications or other inorganic crystals, or fibrous tissue. Carefully evaluating the presence and pattern of T2 hypointensity in soft tissue masses and considering potential causes in their associated clinical contexts can help to narrow the differential diagnosis among neoplastic and non-neoplastic possibilities. These include endometriosis, aneurysmal bone cysts, tenosynovial giant cell tumor, arteriovenous malformation and pseudoaneurysm, calcium pyrophosphate and hydroxyapatite deposition diseases, tumoral calcinosis, gout, amyloidosis, hemangiomas with phleboliths, low-grade fibromyxoid sarcoma, ossifying fibromyxoid tumor, collagenous fibroma, desmoid-type fibromatosis, myxofibrosarcoma, peripheral nerve sheath tumors, dedifferentiated liposarcoma, and treated sarcoma.Organophosphate pesticides (OPs) are known to inhibit acetylcholine esterase (AChE), a critical effect used to establish health-based guidance values. This study developed a combined in vitro-in silico approach to predict AChE inhibition by the OP profenofos in rats and humans. A physiologically based kinetic (PBK) model was developed for both species. Parameter values for profenofos conversion to 4-bromo-2-chlorophenol (BCP) were derived from in vitro incubations with liver microsomes, liver cytosol, and plasma from rats (catalytic efficiencies of 1.1, 2.8, and 0.19 ml/min/mg protein, respectively) and humans (catalytic efficiencies of 0.17, 0.79, and 0.063 ml/min/mg protein, respectively), whereas other chemical-related parameter values were derived using in silico calculations. The rat PBK model was evaluated against literature data on urinary excretion of conjugated BCP. Concentration-dependent inhibition of rat and human AChE was determined in vitro and these data were translated with the PBK models to predicted dose-dependent AChE inhibition in rats and humans in vivo. Comparing predicted dose-dependent AChE inhibition in rats to literature data on profenofos-induced AChE inhibition revealed an accurate prediction of in vivo effect levels. Comparison of rat predictions (BMDL10 of predicted dose-response data of 0.45 mg/kg bw) and human predictions (BMDL10 of predicted dose-response data of 0.01 mg/kg bw) suggests that humans are more sensitive than rats, being mainly due to differences in kinetics. Altogether, the results demonstrate that in vivo AChE inhibition upon acute exposure to profenofos was closely predicted in rats, indicating the potential of this novel approach method in chemical hazard assessment.

To assess the relationship between MRE stiffness of prostate cancer (PCa) and the extent of lymph node metastasis (LNM) in patients with PCa undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

The local institutional review board approved this retrospective study. We retrospectively analyzed 49 patients, who had undergone MRE, mpMRI and pelvic MRI on a 3.0T MRI scanner, with histopathological confirmed PCa after RP (from June 2015 to December 2019). For each patient, preoperative clinical data and characteristics of MRE, mpMRI and pelvic MRI were recorded. Independent-samples t test, univariate and multivariate logistic regression analyses were performed. And receiver operating characteristic (ROC) analysis were performed to compare the diagnostic performances of multivariate models with the Briganti 2019 nomogram.

PCa MRE stiffness and maximum diameter were independent predictors of LNM. When PCa MRE stiffness at 60Hz (odds ratio [OR] = 20.223, P = 0.013) and maximum diameter (OR = 4.575, P = 0.046) were combined, the sensitivity and specificity were 100% and 91.9% to predict LNM. When PCa MRE stiffness at 90Hz (OR = 7.920, P = 0.013) and maximum diameter (OR = 2.810, P = 0.045) were combined, the sensitivity and specificity were 100% and 86.5% to predict LNM. The areas under curves (AUCs) of the combinations were higher than the AUC of the Briganti 2019 nomogram (0.982 vs. 0.904, P = 0.040 [60Hz]; 0.975 vs. 0.904, P = 0.060 [90Hz], respectively).

MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.

MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.Magnetic resonance imaging (MRI) is the current reference standard imaging modality for restaging rectal cancer after neoadjuvant chemoradiation and is used to guide clinical management decisions. This pictorial essay provides an illustrative atlas of the key MRI features used to assess rectal cancer after treatment. MRI findings of residual tumor including non-mucinous, mucinous, and signet-ring cell adenocarcinoma subtypes are correlated with histopathology. Imaging appearances of treatment changes that mimic residual tumor in the setting of confirmed pathological complete response at resection are illustrated. Treatment complications are also shown. Knowledge of these imaging findings and their importance may help radiologists comply with all elements of the structured reporting templates proposed by the Rectal Cancer Disease Focused Panel of the Society of Abdominal Radiology and by the European Society of Gastrointestinal and Abdominal Radiology.Mass photometry (MP) is a relatively new experimental technique with a quickly expanding list of applications. Using optical detection, MP measures the mass of individual molecules to obtain molecular mass distributions of proteins and other biomolecules in solution. The combination of speed, sensitivity, and very low sample consumption with label- and immobilization-free detection sets MP apart from other analytical methods. An increasing number of laboratories incorporates mass photometry as a routine sample analysis technique. However, MP measurements can sometimes be challenging, especially for users without previous experience with single-molecule techniques. Here, we present a protocol for the determination of protein molecular mass distributions by MP. It describes the sample and materials preparation as well as data collection and analysis. The advantages and limitations of this technique and the potential sources of artifacts are also given. This protocol can be used by new MP users and serve as a checklist for laboratories routinely performing MP experiments to guide consistent data collection and documentation.Among elderly participants from the Cardiovascular Health Study, we found that non-esterified trans fatty acid levels had a significant prospective association with hip fracture risk. Other non-esterified fatty acid classes were not associated with hip fracture risk.

Serum non-esterified fatty acids (NEFAs) are bioactive metabolic intermediates that can be taken up by bone tissue. Their associations with hip fracture risk have not been previously examined.

Thirty-five individual NEFAs in five classes (saturated [SFA], mono-un-saturated [MUFA], poly-unsaturated n-6 and n-3 [PUFA], and trans-FA) were measured in Cardiovascular Health Study participants (n = 2139, mean age 77.8 years) without known diabetes. The multivariable associations of NEFA levels with hip fracture risk were evaluated in Cox hazards models.

We documented 303 incident hip fractures during 11.1 years of follow-up. Among the five NEFA classes, total trans FA levels were positively associated with higher hip fracture risk (HR 1.17 [95% CI, 1.04, 1.31; p = 0.01] per one standard deviation higher level). The SFA lignoceric acid (240) was positively associated with higher risk (HR 1.09 [1.04, 1.1]; p < 0.001), while behenic (220) and docosatetraenoic (224 n6) acids were associated with lower risk (HR 0.76 [0.61, 0.94]; p = 0.01; 0.84 [0.70, 1.00]; p = 0.05, respectively).

Total plasma trans NEFA levels are related to hip fracture risk, suggesting an unrecognized benefit of their systematic removal from food. Novel associations of individual NEFAs with hip fracture risk require confirmation in other cohort studies.

Total plasma trans NEFA levels are related to hip fracture risk, suggesting an unrecognized benefit of their systematic removal from food. Novel associations of individual NEFAs with hip fracture risk require confirmation in other cohort studies.

Diabetes is a major burden on Australia's Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. MicroRNAs (miRNAs) are key players in the regulation of angiogenesis. HDL-cholesterol (HDL-c) levels are inversely associated with the risk of developing diabetic complications and HDL can carry miRNAs. HDL-miRNA profiles differ in disease states and may present as biomarkers with the capacity to act as bioactive signalling molecules. Recent studies have demonstrated that HDL becomes dysfunctional in a diabetic environment, losing its vasculo-protective effects and becoming more pro-atherogenic. We sought to determine whether HDL-associated miRNA profiles and HDL functionality were predictive of the severity of diabetic vascular complications in Australia's Indigenous population.

HDL was isolated from plasma samples from Indigenous participants without diabetes ('Healthy'), with type 2 diabetes mellitus ('T2DM') and with diabetes-associated macrovascular complications (specifically peripheral artery disease, 'T2DM+Comp').

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