Notes

Exploration around the solid-phase synthesis regarding silybin prodrugs and their timed-release.
The removal access was new PCN access (n = 8), the tract missing PCN catheter (n = 3), pre-existing PCN access (n = 2), and percutaneous dissection (n = 1). The removal success rate was 92.9% (13/14) with either a simple (n = 8) or modified (n = 4; combination of a snare and guide wire is used) snare technique or a direct forceps grasp (n = 1). The mean procedure time for successful cases was 14.2 min (range 7-25 min). Procedure-related hematoma with (n = 2) or without (n = 1) renal pelvis injury occurred in three patients, which were all self-limited within one week.

Percutaneous antegrade removal is safe and effective for urinary tract foreign bodies.
Percutaneous antegrade removal is safe and effective for urinary tract foreign bodies.
Previous studies reported that single vascular atherosclerosis was an effective indicator for white matter lesions (WMLs).

To investigate the added value of femoral atherosclerosis for determining severity of WMLs by carotid atherosclerosis using three-dimensional vessel wall magnetic resonance imaging (MRI).

Elderly individuals without cardiovascular symptoms within the previous six months were recruited. The plaque features of carotid and femoral arteries were evaluated and compared between individuals with WML score ≤ 3 and those with WML score > 3. Logistic regression and receiver operating characteristic (ROC) analyses were used to determine the value of plaque features in discriminating WMLs with score > 3.

In total, 112 individuals (49 men, mean age 72.0±5.6 years) were included. Participants with a WML score > 3 showed a significantly greater carotid wall area and femoral artery stenosis and higher incidence of carotid calcification and femoral artery calcification and lipid-rich necrotic cores (LRNC) compared to those with a WML score ≤ 3 (all
 < 0.05). Carotid artery calcification and femoral artery calcification, LRNC, and stenosis were found to be significantly associated with severe WMLs before and after adjustment for clinical factors (odds ratio 1.51-3.79, all
 < 0.05). ROC analysis showed, in discriminating severe WMLs, the area under the curve increased from 0.615 to 0.754 after combining femoral artery LRNC and stenosis with carotid calcification compared to the carotid calcification alone.

Characteristics of femoral artery atherosclerosis determined by vessel wall MRI have added value for carotid atherosclerosis in determining the severity of WMLs.
Characteristics of femoral artery atherosclerosis determined by vessel wall MRI have added value for carotid atherosclerosis in determining the severity of WMLs.
Validated non-invasive examinations are necessary to monitor liver fibrosis in children with biliary atresia (BA) after the Kasai procedure.

To evaluate the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and the serologic biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for evaluating native liver fibrosis in children with BA.

We retrospectively reviewed same-day 2D-SWE and TE liver stiffness (LS) measurements of 63 patients with BA who underwent the Kasai procedure. The APRI and FIB-4 score were computed. Hepatic fibrosis was categorized into three clinical categories based on the ultrasound (US) hepatic morphology and clinical manifestations of liver cirrhosis I, pre-cirrhotic liver state (n = 15); II, US and/or clinical signs of liver cirrhosis with compensated liver function (n = 27); and III, liver cirrhosis with decompensated liver function (n = 21). We compared area under the receiver operating characteristic curve (AUC) data among 2D-SWE, TE, APRI, and FIB-4 score. Combined evaluation of serologic fibrosis indices and US elastography was conducted and AUCs of combinations were analyzed.

2D-SWE, TE, APRI, and FIB-4 score showed good to excellent diagnostic accuracy for differentiating clinical categories (AUCs 0.779-0.955). AUC values were significantly increased after adding TE to FIB-4 score for detecting liver cirrhosis (
 = 0.02).

2D-SWE, TE, APRI, and FIB-4 score are accurate non-invasive markers for monitoring native liver fibrosis in patients with BA. Combined use of serologic markers and US elastography could yield more accurate diagnoses of liver fibrosis than serologic markers alone.
2D-SWE, TE, APRI, and FIB-4 score are accurate non-invasive markers for monitoring native liver fibrosis in patients with BA. Combined use of serologic markers and US elastography could yield more accurate diagnoses of liver fibrosis than serologic markers alone.Tick-borne encephalitis is an important human arbovirus neuroinfection spread across the Northern Eurasia. Inhibitors of tick-borne encephalitis virus (TBEV) strain Absettarov, presumably targeting E protein n-octyl-β-d-glucoside (β-OG) pocket, were reported earlier. In this work, these inhibitors were tested in vitro against seven strains representing three main TBEV subtypes. The most potent compound, 2-[(2-methyl-1-oxido-5,6,7,8-tetrahydroquinazolin-4-yl)amino]-phenol, showed EC50 values lower than 22 µM against all the tested strains. Nevertheless, EC50 values for virus samples of certain strains demonstrated a substantial variation, which appeared to be consistent with the presence of E protein not only in infectious virions, but also in non-infectious and immature virus particles, protein aggregates, and membrane complexes.
There is increasing evidence that improving patient trust in doctors can improve patients' use of healthcare services, compliance and continuing engagement with care -particularly for chronic diseases. Consequently, much of the current literature on trust in therapeutic relationships focuses on factors shaping doctors' trustworthiness. However, few studies on this issue have been conducted among rural populations in low-income Africa, where health service delivery, cultural norms and patient expectations differ from those in high-income countries. This study examined patients' perspectives of factors that shape doctors' trustworthiness in rural Tanzania in the context of hypertension care.

A qualitative inquiry using in-depth interviews was conducted between 2015 and 2016 in two characteristically rural districts of Tanzania. Data were analysed thematically.

The accounts of 34 patients from a Western-based care setting were examined. There was broad consensus about factors shaping doctors' trustworthineociated with non-communicable diseases in rural low-income Africa.
Good interpersonal behaviours and good technical skills are important in shaping patients' judgements of doctors' trustworthiness in rural Tanzania. The present findings provide useful insights for designing interventions to improve patient trust in doctors to address challenges associated with non-communicable diseases in rural low-income Africa.A time-dependent postextraction differential acceleration (PEDA) potential was used to temporally focus increasingly heavy ions in a stigmatic imaging mass spectrometer, allowing them to be imaged with high mass and spatial resolutions over a broad mass-to-charge (m/z) range. By applying a linearly rising potential to the ion extraction electrode, sequential m/z ratios were subjected to a changing electric field, allowing their foci to coincide at the detector. Using this approach, at least 75% of the maximum mass resolution was obtained over a 300-600 Da range when the ion microscope was focused around 450 Da, representing more than a 10-fold increase over the conventional single-field PEDA method.Nanostructured metal catalysts have attracted great interest due to their extraordinary performance for electrocatalysis including electrochemical nitrogen reduction (ENRR). However, their working mechanisms for ENRR are still not fully understood. Herein, seven monofaceted polyhedral Au nanocrystals were synthesized and systemically compared to elucidate the relation between Au crystal facets and NRR performance. It is found that polyhedra with high-index facets catalytically outperform those with low-index facets. Specifically, Au nanostars enclosed with (321) facets show a high NH3 production rate of 2.6 μg h-1 cm-2 (20 μg h-1 mg-2) and faradaic efficiency of 10.2% at -0.2 V, which are 3.1- and 5.1-folds larger than those of nanocubes enclosed with (100) facets. As revealed by theoretical investigation, a larger energy barrier for reduction of H+ to H* (ΔGH*) hinders occurrence of HER on the Au(321) surface, thus ensuring better NRR selectivity. Meanwhile, a lower energy barrier for formation of N2H2* on the catalyst surface and a larger energy barrier for decomposing the formed N2H2* back into N2 and 2H* jointly favor a higher NH3 production rate. This study provides mechanistic insights into ENRR and rational design of metal nanocrystals for electrocatalysis.The cytochromes P450 are heme-dependent enzymes that catalyze many vital reaction processes in the human body related to biodegradation and biosynthesis. They typically act as mono-oxygenases; however, the recently discovered P450 subfamily TxtE utilizes O2 and NO to nitrate aromatic substrates such as L-tryptophan. A direct and selective aromatic nitration reaction may be useful in biotechnology for the synthesis of drugs or small molecules. Details of the catalytic mechanism are unknown, and it has been suggested that the reaction should proceed through either an iron(III)-superoxo or an iron(II)-nitrosyl intermediate. To resolve this controversy, we used stopped-flow kinetics to provide evidence for a catalytic cycle where dioxygen binds prior to NO to generate an active iron(III)-peroxynitrite species that is able to nitrate l-Trp efficiently. We show that the rate of binding of O2 is faster than that of NO and also leads to l-Trp nitration, while little evidence of product formation is observed from the iron(II)-nitrosyl complex. To support the experimental studies, we performed density functional theory studies on large active site cluster models. The studies suggest a mechanism involving an iron(III)-peroxynitrite that splits homolytically to form an iron(IV)-oxo heme (Compound II) and a free NO2 radical via a small free energy of activation. The latter activates the substrate on the aromatic ring, while compound II picks up the ipso-hydrogen to form the product. The calculations give small reaction barriers for most steps in the catalytic cycle and, therefore, predict fast product formation from the iron(III)-peroxynitrite complex. These findings provide the first detailed insight into the mechanism of nitration by a member of the TxtE subfamily and highlight how the enzyme facilitates this novel reaction chemistry.Biofunctional proteins such as active enzymes and therapeutic proteins show tremendous promise in disease treatment. However, intracellular delivery of proteins is facing substantial challenges owing to their vulnerability to degradation and denaturation and the presence of various biological barriers such as their low membrane transport efficiency. Herein, we report a magnetically driven and redox-responsive nanotransporter (MRNT) for highly efficient intracellular delivery of biofunctional proteins. The MRNT has remarkably high cargo capacity, compared with that without nanoscale cargo compartments. We have demonstrated the directional and dynamic motion of the MRNT using both nanoparticle tracking analysis and magnetic driving evaluation. Moreover, the active MRNT can translocate into the cytosol and sense the reducing cytosolic environment to discharge protein cargoes autonomously. The internalization mechanism of the MRNT has been studied using endocytosis inhibitors. Crizotinib Under the magnetic drive, the MRNT can promote a protein transduction efficiency of over 95%, and the intracellular protein delivery by the active MRNT shows significantly higher (∼4 times) enzymatic activity and therapeutic efficiency than those achieved by the static ones.
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