Microwave-assisted synthesis of polyheterocyclic-fused quinoline-2-thiones through the annulation of
ortho
-heteroaryl anilines and CS
2
was realized in water without using any catalysts and ...additives. The desired products were obtained in high yields through simple filtration. A remarkable
E
-factor of 0.45 and an EcoScale score of 85.5 were obtained.
Microwave-assisted synthesis of polyheterocyclic-fused quinoline-2-thiones through the annulation of
ortho
-heteroaryl anilines and CS
2
was realized in water without using any catalysts and additives.
The role of autophagy in the cardioprotection conferred by ischemic preconditioning (IPC) has been well described. This study aimed to investigate the changes in autophagy levels during the ...cardioprotective effects initiated by exercise preconditioning (EP).Rats were randomly divided into 4 groups: group C (control), group EP, group EE (exhaustive exercise), and group EP + EE (EP pretreatment at 0.5 hours before EE). The EP protocol included 4 periods of 10 minutes of treadmill running each at 30 m/minute with intervening 10 minute periods of rest. Hematoxylin-basic fuchsin-picric acid (HBFP) staining and plasma levels of cardiac troponin I (cTnI) were used to evaluate the ischemia-hypoxia injury in rat myocardium. Alteration levels in several autophagy proteins in the left ventricular myocardium were analyzed by Western blot. The phasic alterations of autophagy levels during EP-initiated cardioprotective phase were also examined.Compared with group C, the ischemia-hypoxia positive areas and IOD value in HBFP-staining and cTnI plasma levels increased significantly in group EE. Compared with group EE, the ischemia-hypoxia injury was markedly attenuated in group EP + EE. Compared with group C, the LC3-II/LC3-I ratio, a marker of autophagosome formation, was reduced in group EE, but the LC3-II/LC3-I ratio remained unaltered in group EP + EE. Furthermore, the LC3-II/LC3-I ratio increased significantly at 2 hours during the cardioprotective phase after EP.These results suggest that the activated autophagy level during the EP-initiated cardioprotective phase may be partly involved in the cardioprotective effects by maintaining a normal autophagy basal level during the subsequent exhaustive exercise in rat myocardium.
Background and Purpose
Salinomycin is a well‐known inhibitor of human cancer stem cells (CSCs). However, the molecular mechanism(s) by which salinomycin targets colorectal CSCs is poorly understood. ...Here, we have investigated underlying antitumour mechanisms of salinomycin in colorectal cancer cells and three tumour models.
Experimental Approach
The inhibitory effect of salinomycin on the Wnt/β‐catenin pathway was analysed with the SuperTopFlash reporter system. The mRNA expression of Wnt target genes was evaluated with real‐time PCR. Effects of salinomycin on β‐catenin/TCF4E interaction were examined using co‐immunoprecipitation and an in vitro GST pull‐down assay. Cell proliferation was determined by BrdU incorporation and soft agar colony formation assay. The stemness of the cells was assessed by sphere formation assay. Antitumour effects of salinomycin on colorectal cancers was evaluated with colorectal CSC xenografts, APCmin/+ transgenic mice, and patient‐derived colorectal tumour xenografts.
Key Results
Salinomycin blocked β‐catenin/TCF4E complex formation in colorectal cancer cells and in an in vitro GST pull‐down assay, thus decreasing expression of Wnt target genes. Salinomycin also suppressed the transcriptional activity mediated by β‐catenin/LEF1 or β‐catenin/TCF4E complex and exhibited an inhibitory effect on the sphere formation, proliferation, and anchorage‐independent growth of colorectal cancer cells. In colorectal tumour xenografts and APCmin/+ transgenic mice, administration of salinomycin significantly reduced tumour growth and the expression of CSC‐related Wnt target genes including LGR5.
Conclusions and Implications
Our study suggested that salinomycin could suppress the growth of colorectal cancer by disrupting the β‐catenin/TCF complex and thus may be a promising agent for colorectal cancer treatment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized.
Hospitalized patients with COVID-19 in Zhejiang ...Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared.
Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median interquartile range {IQR} age, 47.0 35.0-55.0 years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups.
We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.
Background
Large‐ and small‐headed sperm are common morphological abnormalities. If different sperm staining methods affect sperm size, they will make a difference in the accuracy of sperm ...morphological analysis results. In this case, the normal reference values of sperm head parameters for different staining methods should be established.
Methods
Six sperm staining methods, including Papanicolaou, Diff‐Quik, Shorr, Hematoxylin–eosin (HE), Wright, and Wright‐Giemsa staining, were used to stain the sperm smears of 25 semen samples, respectively. Sperm head parameter's length (L), width (W), area (A), perimeter, acrosomal area (Ac), and the derived values L/W and Ac/A of 2500 sperm (100 for each specimen) per staining method were measured by a computer‐aided sperm morphological analysis system.
Results
The highest sperm head length and width were observed with the Wright‐Giemsa and Wright staining, followed by the Diff‐Quik. The lowest sperm head length and width were observed with the Papanicolaou staining, and the sperm head length and width of HE and Shorr staining were between those of Papanicolaou and Diff‐Quik staining. There was the same trend in changes in sperm head area and perimeter. Diff‐Quik and Shorr staining could clearly distinguish acrosome and nucleus, followed by HE staining, whereas the boundary between acrosome and nucleus was not evident in Papanicolaou, Wright, and Wright‐Giemsa staining.
Conclusion
Different staining methods influence sperm size, and the normal reference values of sperm head parameters of each staining method should be established. Diff‐Quik and Shorr staining may be suitable methods for routine sperm morphological analysis.
The highest sperm head length, width, area, and perimeter were observed with the Wright‐Giemsa and Wright staining, followed by the Diff‐Quik, Hematoxylin–eosin, and Shorr staining, and the lowest sperm head size was observed with the Papanicolaou staining. The staining effects of the six sperm staining methods were also different. Diff‐Quik and Shorr staining could clearly distinguish acrosome and nucleus, followed by HE staining, while the boundary between acrosome and nucleus was not evident in Papanicolaou, Wright, and Wright‐Giemsa staining.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To analyze changes in the detection of parainfluenza virus (PIV) in children hospitalized with acute respiratory tract infection (ARTI) during 2014–2022 in Hubei Province, and explore the impact of ...the universal two‐child policy and the public health measures against COVID‐19 epidemic on the prevalence of PIV in China. The study was conducted at the Maternal and Child Health Hospital of Hubei Province. Children aged <18 years with ARTI admitted from January 2014 to June 2022 were enrolled. The infection of PIV was confirmed by the direct immunofluorescence method in nasopharyngeal specimens. Adjusted logistic regression models were used to analyze the influence of the universal two‐child policy implementation and public health measurements against COVID‐19 on PIV detection. Totally 75 128 inpatients meeting the criteria were enrolled in this study from January 2014 to June 2022 with an overall PIV positive rate of 5.5%. The epidemic seasons of PIV prevalence lagged substantially in 2020. A statistically significant higher positive rate of PIV was observed in 2017–2019 compared to that in 2014–2015 (6.12% vs 2.89%, risk ratio = 2.12, p < 0.001) after the implementation of the universal two‐child policy in 2016. A steep decline occurred in PIV positive rate during the COVID‐19 epidemic in 2020 (0.92% vs 6.92%, p < 0.001) and it rebounded during the regular epidemic prevention and control period in 2021–2022 (6.35%, p = 0.104). In Hubei Province, the implementation of the universal two‐child policy might have led to an increase of PIV prevalence, and public health measures during the COVID‐19 epidemic might have influenced the fluctuation in PIV detection since 2020.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Preoperative evaluation of the consistency of pituitary macroadenomas is important for neurosurgeons to prepare the surgical plan.
Purpose
To evaluate the diagnostic performance of texture ...analysis (TA) of diffusion‐weighted imaging (DWI) at a standard b‐value (b = 1000 s/mm2) and a high b‐value (b = 2000 s/mm2) for their ability to assess the tumor consistency of pituitary macroadenomas.
Study Type
Retrospective.
Population/Subjects
Fifty patients with histologically confirmed pituitary macroadenomas were classified as soft (n = 37) or hard (n = 13) types.
Field Strength/Sequence
Coronal T2‐weighted imaging (T2WI), Readout Segmentation of Long Variable Echo‐trains (RESOLVE) DWI at b = 1000 s/mm2 and b = 2000 s/mm2 were acquired with 3.0T MRI.
Assessment
The corresponding apparent diffusion coefficient (ADC) maps (ADC1000 and ADC2000) were registered to T2WI. Regions of interest (ROIs) were manually drawn along the solid part of the tumor from the coregistered T2WI‐ADC images. The texture parameters from T2WI, ADC1000, and ADC2000 were acquired.
Statistical Tests
The texture parameters were compared between the two types by using unpaired Student's t‐test. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to assess their diagnostic performance.
Results
Significant differences in TA parameters of ADC1000 and ADC2000 were observed between soft and hard types (P < 0.05 for all), whereas the TA of T2WI resulted in no significant difference (P > 0.05 for all). TA of ADC2000 provided a superior diagnostic performance compared with that of ADC1000 (P = 0.038). A combination of mean value and entropy of ADC2000 yielded an AUC, a sensitivity, and a specificity of 0.911, 78.4% and 92.3%, respectively.
Data Conclusion
TA of ADC values were useful for assessing the tumor consistency of pituitary macroadenomas. ADC2000 may facilitate better type discrimination.
Level of Evidence: 3
Technical Efficacy Stage: 2
J. Magn. Reson. Imaging 2020;51:1507–1513.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial.
Purpose
To investigate the clinical factors ...associated with hyperperfusion, and the 90‐day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients.
Study Type
Retrospective.
Population/Subjects
Fifty‐four AIS patients who underwent mechanical thrombectomy.
Field Strength/Sequence
Time‐of‐flight MR angiography, pulsed arterial spin labeling (ASL), diffusion‐weighted imaging (DWI), and susceptibility‐weighted imaging were performed at 3.0T within 1 week after thrombectomy.
Assessment
Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0–2.
Statistical Tests
The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90‐day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver‐operating‐characteristic curves.
Results
Thirty‐six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS24h) (P < 0.05). A higher incidence of hemorrhage transformation was observed in patients with hyperperfusion than those without (63.9% vs. 50.0%), but no significant difference was found (P = 0.327). NIHSS24h (odds ratio OR, 0.75, 95% confidence interval CI 0.62–0.91, P < 0.05), lesion volume on diffusion‐weighted imaging (OR, 0.97, 95% CI 0.95–1.00, P < 0.05), and hyperperfusion on ASL (OR, 9.8, 95% CI 1.7–55.3, P < 0.05) were independent variables for predicting good functional outcomes.
Data Conclusion
Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy.
Level of Evidence
4
Technical Efficacy Stage
2
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) remained unclear. We aimed to profile the metabolic alterations in urine of SFTS patients and provide new evidence for its ...pathogenesis.
A case-control study was conducted in the 154th hospital in China. Totally 88 cases and 22 controls aged ≥ 18 years were enrolled. The cases were selected from laboratory-confirmed SFTS patients. The controls were selected among SFTSV-negative population. Those with diabetes, cancer, hepatitis and other sexually transmitted diseases were excluded in both groups. Fatal cases and survival cases were 1:1 matched. Inter-group differential metabolites and pathways were obtained, and the inter-group discrimination ability was evaluated.
Tryptophan metabolism and phenylalanine metabolism were the top one important metabolism pathway in differentiating the control and case groups, and the survival and fatal groups, respectively. The significant increase of differential metabolites in tryptophan metabolism, including 5-hydroxyindoleacetate (5-HIAA), L-kynurenine (KYN), 5-hydroxy-L-tryptophan (5-HTP), 3-hydroxyanthranilic acid (3-HAA), and the increase of phenylpyruvic acid and decrease of hippuric acid in phenylalanine metabolism indicated the potential metabolic alterations in SFTSV infection. The increase of 5-HIAA, KYN, 5-HTP, phenylpyruvic acid and hippuric acid were involved in the fatal progress of SFTS patients.
Tryptophan metabolism and phenylalanine metabolism might be involved in the pathogenesis of SFTSV infection. These findings provided new evidence for the pathogenesis and treatment of SFTS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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