Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium‐catalyzed highly ...enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom‐economical approach to an array of 2‐arylpropanoic acids including several commonly used non‐steroidal anti‐inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2‐arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio‐ and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate‐limiting step.
A Pd‐catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water for the synthesis of 2‐arylpropanoic acids has been developed. Several non‐steroidal anti‐inflammatory drugs including ibuprofen, naproxen, flurbiprofen, fenoprofen, and ketoprofen were synthesized in high yields and ees in gram scale.
Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their ...dynamic changes during the treatment, platelet‐to‐lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single‐center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)‐19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single‐center case series of the 30 hospitalized patients with confirmed COVID‐19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID‐19.
Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a ...promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear.
To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM.
Prospective.
Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD).
3 T/ T2 weighted imaging (T
WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).
The parameters derived from IVIM-DWI (true diffusion coefficient D, pseudo-diffusion coefficient D*, and pseudo-diffusion fraction f) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy DR, fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively.
Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant.
The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively).
The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM.
2 TECHNICAL EFFICACY: Stage 2.
Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common ...subtypes of SRMs might be a potential score extension.
To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs.
Retrospective.
797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses.
3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging.
Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions.
Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05.
The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993).
The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool.
4.
Stage 2.
Background
Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC).
Purpose
To develop and validate an MRI‐based radiomic model ...for preoperative predicting WHO/ISUP nuclear grade in ccRCC.
Study Type
Retrospective.
Population
In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned.
Field Strength/Sequence
Pretreatment 3.0T renal MRI. Imaging sequences were fat‐suppressed T2WI, contrast‐enhanced T1WI, and diffusion weighted imaging.
Assessment
Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high‐grade ccRCC.
Statistical Tests
The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics.
Results
The radiomic signature showed good performance in discriminating high‐grade (grades 3 and 4) from low‐grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high‐grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05).
Data Conclusion
Multiparametric MRI‐based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions.
Level of Evidence
3
Technical Efficacy Stage
2
Online health information is critical during pandemics. Previous research has focused on examining antecedents or consequences of particular information behaviors (e.g., seeking, sharing), but the ...process by which one information behavior influences or transforms into other information behaviors remains poorly understood. Guided by theories of information behavior and the literature on online misinformation, this study proposes an interaction model of online information behaviors that theorizes relationships among online information scanning, misinformation exposure, misinformation elaboration, information sharing, and information avoidance. Conducting a two-wave representative panel survey in Hong Kong during the COVID-19 pandemic (N = 1501), we found that online information scanning at Wave 1 had a direct, positive impact on misinformation exposure and information sharing at Wave 2, while it did not have an impact on information avoidance at Wave 2. Additionally, misinformation exposure was positively related to both information sharing and information avoidance at Wave 2. Importantly, we underlined that evaluations of crisis-related misinformation are aided by misinformation elaboration, which plays a moderating role in catalyzing appropriate information behaviors. Results of this study could help scholars and practitioners propose evidence-based interventions for enhancing the public's ability to manage crisis information on the Internet in times of heightened uncertainty.
•This study proposes an interaction model of online information behaviors during crises.•A two-wave representative panel survey was conducted in Hong Kong to test the model.•Online information scanning increased information sharing.•Misinformation exposure increased information sharing and avoidance.•We highlighted the moderating role of misinformation elaboration in information management.
To implant in the uterus, the mammalian embryo first specifies two cell lineages: the pluripotent inner cell mass that forms the fetus, and the outer trophectoderm layer that forms the placenta
. In ...many organisms, asymmetrically inherited fate determinants drive lineage specification
, but this is not thought to be the case during early mammalian development. Here we show that intermediate filaments assembled by keratins function as asymmetrically inherited fate determinants in the mammalian embryo. Unlike F-actin or microtubules, keratins are the first major components of the cytoskeleton that display prominent cell-to-cell variability, triggered by heterogeneities in the BAF chromatin-remodelling complex. Live-embryo imaging shows that keratins become asymmetrically inherited by outer daughter cells during cell division, where they stabilize the cortex to promote apical polarization and YAP-dependent expression of CDX2, thereby specifying the first trophectoderm cells of the embryo. Together, our data reveal a mechanism by which cell-to-cell heterogeneities that appear before the segregation of the trophectoderm and the inner cell mass influence lineage fate, via differential keratin regulation, and identify an early function for intermediate filaments in development.
Summary
Rice (Oryza sativa L.) has two ecotypes, upland and lowland rice, that have been observed to show different tolerance levels under flooding stress. In this study, two rice cultivars, upland ...(Up221, flooding‐intolerant) and lowland (Low88, flooding‐tolerant), were initially used to study their molecular mechanisms in response to flooding germination. We observed that variations in the OsCBL10 promoter sequences in these two cultivars might contribute to this divergence in flooding tolerance. Further analysis using another eight rice cultivars revealed that the OsCBL10 promoter could be classified as either a flooding‐tolerant type (T‐type) or a flooding‐intolerant type (I‐type). The OsCBL10 T‐type promoter only existed in japonica lowland cultivars, whereas the OsCBL10 I‐type promoter existed in japonica upland, indica upland and indica lowland cultivars. Flooding‐tolerant rice cultivars containing the OsCBL10 T‐type promoter have shown lower Ca2+ flow and higher α‐amylase activities in comparison to those in flooding‐intolerant cultivars. Furthermore, the OsCBL10 overexpression lines were sensitive to both flooding and hypoxic treatments during rice germination with enhanced Ca2+ flow in comparison to wild‐type. Subsequent findings also indicate that OsCBL10 may affect OsCIPK15 protein abundance and its downstream pathways. In summary, our results suggest that the adaptation to flooding stress during rice germination is associated with two different OsCBL10 promoters, which in turn affect OsCBL10 expression in different cultivars and negatively affect OsCIPK15 protein accumulation and its downstream cascade.
Significance Statement
This study identifies that OsCBL10 is able to communicate with upstream calcium signaling and downstream flooding responses by affecting OsCIPK15 protein accumulation or stability. The variation in OsCBL10 promoter regions could be a general mechanism in Sub1A‐deficient lowland japonica cultivars in response to flooding germination.
Metal-organic frameworks (MOFs) are built using various organic ligands and metal ions (or clusters). With properties of high porosity, tunable chemical composition, and potential for post-synthetic ...modification, they have been applied in biomedicine, especially in bio-sensing, bio-imaging, and drug delivery. Since organic ligands and metal centers (ions or clusters) in the structure of MOFs can directly influence the property, function, and performance of MOFs, strict screening of organic ligands and metal centers is necessary. Especially, to improve the application of MOFs in the field of biomedicine, biocompatible organic ligands with low toxicity are desirable. In recent years, biological metal-organic frameworks (bio-MOFs) with ideal biocompatibility and diverse functionality have attracted wide attention. Endogenous biomolecules, including nucleobases, amino acids, peptides, proteins, porphyrins and saccharides, are employed as frameworks for MOF construction. These biological ligands coordinate with diverse metal centers in different ways, leading to the structural diversity of bio-MOFs. In this review, we summarize the organic ligand selectivity in constructing different types of bio-MOFs and their influence in biomedical applications with attractive new functions.
This review introduces biological metal-organic frameworks (bio-MOFs) designed and prepared using biological ligands for bio-sensing, bio-imaging, and drug delivery.
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