Osteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process, which is regulated by various factors including microRNAs. Our preliminary data showed that the expression of ...endogenous miR-20a was increased during the course of osteogenic differentiation. Simultaneously, the expression of osteoblast markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated whereas adipocyte markers PPARγ and osteoblast antagonist, Bambi and Crim1, were downregulated, thereby suggesting that miR-20a plays an important role in regulating osteoblast differentiation. To validate this hypothesis, we tested its effects on osteogenic differentiation by introducing miR-20a mimics and lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We performed bioinformatics analysis and predicted that PPARγ, Bambi and Crim1 would be potential targets of miR-20a. PPARγ is a negative regulator of BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway. Furthermore, we confirmed that all these molecules were indeed the targets of miR-20a by luciferase reporter, quantitative RT-PCR and western blot assays. Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence of PPARγ, Bambi or Crim1 by specific siRNAs. Taken together, for the first time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPARγ, Bambi and Crim1, the negative regulators of BMP signaling.
This study investigated whether the appropriate antibiotics therapy affects the fecal excretion time in pediatric salmonellosis of different severities and explored the factors associated with the ...fecal excretion time of nontyphoid Salmonella.
Between 2012 and 2017, admitted children with nontyphoid salmonellosis who consented to receive consecutive stool cultures every 4–7 days until 2 consecutive negative results were obtained were enrolled. Patients were stratified into no, appropriate (bacteremia or severe patients receiving antibiotics active in vitro), and inappropriate antibiotics (patients with mild or moderate severity receiving antibiotics or severe receiving antibiotics resistant in vitro) therapy groups. A previously proposed severity score was used to classify the patients into severe, moderate, and mild severity classes. The demographics, clinical manifestations, laboratory data and severity were compared among the groups. To explore the factors associated with the fecal excretion time of nontyphoid Salmonella, univariate and multivariate analyses were performed using linear regression analysis.
This study enrolled 126 children with nontyphoid salmonellosis; 58 and 18 in the mild and severe classes, respectively. The no, appropriate and inappropriate antibiotics therapy groups comprised 69, 24 and 33 patients, respectively. The mean fecal excretion time was 12.17 days. The appropriate antibiotics therapy group had comparable fecal excretion time with that of no antibiotics group. Age <1 year, increased white blood cell count, decreased hemoglobin, and inappropriate antibiotics therapy significantly prolonged fecal excretion time in univariate analysis (p < 0.05). The multivariate analysis showed that inappropriate antibiotics therapy and decreased hemoglobin significantly prolonged the fecal excretion time.
Inappropriate antibiotics therapy and decreased hemoglobin prolong the fecal excretion time of nontyphoid Salmonella, whereas appropriate antibiotics therapy does not. Continuous monitoring of antibiotic resistance and judicious use of antibiotics in children with nontyphoid salmonellosis are necessary.
Argyrodite-type compounds are renowned for their exceptional thermoelectric performance and ultralow thermal conductivity. While the latter is commonly attributed to the superionic behavior of ...cations, there has been limited research into how cations' static or dynamic behavior affects the thermal transport properties of argyrodites. To address and bridge this research gap, we employ a wide range of measurements and develop ab-initio based machine-learning interatomic potentials to perform large-scale molecular dynamics simulations on Ag8SiTe6 under different temperatures. We highlight the symmetry breaking and lattice-distortion scattering caused by chilled ions at low temperatures and the enhanced ionic diffusion behavior at elevated temperatures endowing argyrodites with superior superionicity and liquid-like thermal conductivity. Our findings also provide valuable insights into the ionic diffusion kinetics and the exotic lattice dynamics of liquid-like thermoelectrics.
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•The liquid-like thermal conductivity of Ag8SiTe6 are unveiled by MD simulations with machine learning interatomic potentials.•The temperature-driven symmetry breaking, lattice distortion, and ionic diffusion behavior in argyrodite are demonstrated.•This work unveils the intricate diffusion kinetics and lattice dynamics inherent in liquid-like thermoelectric materials.
Layered transition metal dichalcogenides (TMDs) are two-dimensional materials exhibiting a variety of unique features with great potential for electronic and optoelectronic applications. The ...performance of devices fabricated with mono or few-layer TMD materials, nevertheless, is significantly affected by surface defects in the TMD materials. Recent efforts have been focused on delicate control of growth conditions to reduce the defect density, whereas the preparation of a defect-free surface remains challenging. Here, we show a counterintuitive approach to decrease surface defects on layered TMDs: a two-step process including Ar ion bombardment and subsequent annealing. With this approach, the defects, mainly Te vacancies, on the as-cleaved PtTe2 and PdTe2 surfaces were decreased by more than 99%, giving a defect density <1.0 × 1010 cm–2, which cannot be achieved solely with annealing. We also attempt to propose a mechanism behind the processes.
Background
The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother‐to‐child HBV transmission is a key step towards hepatitis elimination. ...However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation.
Methods
The maternal and infant outcomes were compared in multi‐centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow‐ups. To explore the dynamic pre‐ and postpartum changes in ALT levels, we used a group‐based trajectory model for analysing data of 332 women from three prospective studies.
Results
After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg‐positive rates among 12‐month‐old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF‐treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%).
Conclusions
TAF effectively reduces mother‐to‐child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment.
Clinical trial number: NCT03695029 (ClinicalTrials.gov).
Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world ...nationwide basis is elusive.
The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT).
The eGFR decreased from baseline (91.4 mL/min/1.73 m
) to EOT (88.4 mL/min/1.73 m
; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m
) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m
(from 112.9 to 106.4 mL/min/1.73 m
; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m
(from 70.0 to 71.5 mL/min/1.73 m
; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m
was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m
; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change.
Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.
Patients with childhood cancer are at increased risk for the development of second cancers.
A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved ...retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed.
We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer.
Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.
The preparation of natural product-inspired nucleoside analogs using solution-phase parallel synthesis is described. The key intermediates containing alkyne and N-protected amino moieties were ...developed to allow for further skeleton and substituent diversity using click chemistry and urea or amide bond formation. Rapid purification was accomplished using solid-phase extraction. The obtained library comprised 80 molecules incorporating two diversity positions and one chiral center, each of which was efficiently prepared in good purity and acceptable overall yield. A bacterial morphology study was also performed.
Traditional Chinese medicine (TCM) formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different ...susceptibility to certain diseases. This study aimed to assess the Yang-Xu constitution using a body constitution questionnaire (BCQ) and clinical blood variables. A BCQ was employed to assess the clinical manifestation of Yang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV) and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs) were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%), while subjects of the other group, named as the sub-healthy group, had three BCs (32%). Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes in Yang-Xu subjects. This study indicated significant biochemical differences in Yang-Xu subjects, which may provide a connection between blood variables and the Yang-Xu BC.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Taiwan. To help clinical physicians to manage patients with HCC, the Taiwan Liver Cancer Association and the ...Gastroenterological Society of Taiwan produced the management consensus guideline for HCC.
The recommendations focus on nine important issues on management of HCC, including surveillance, diagnosis, staging, surgery, local ablation, transarterial chemoembolization/transarterial radioembolization/hepatic arterial infusion chemotherapy, systemic therapy, radiotherapy, and prevention.
The consensus statements were discussed, debated and got consensus in each expert team. And then the statements were sent to all of the experts for further discussion and refinement. Finally, all of the experts were invited to vote for the statements, including the level of evidence and recommendation.
With the development of the management consensus guideline, HCC patients could benefit from the optimal therapeutic modality.
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