Electrocatalytic Cascade Selenylation/Cyclization/Deamination of 2-Hydroxyaryl Enaminones: Synthesis of 3-Selenylated Chromones under Mild Conditions.

Herein, we disclosed a highly efficient pathway toward 3-selenylated chromone derivatives via electrocatalytic cascade selenylation/cyclization/deamination of 2-hydroxyaryl enaminones with diselenides. This method showed mild conditions, easy operation, wide substrate scope, and good functional group tolerance. Furthermore, this electrosynthesis strategy was amendable to scale-up the reaction. Additionally, the preliminary experiments revealed that this reaction probably proceeded via a cation pathway instead of a radical pathway.

MRI-Based Vertebral Bone Quality Score Can Predict the Imminent New Vertebral Fracture After Vertebral Augmentation.

BACKGROUND AND OBJECTIVES: The incidence of imminent new vertebral fracture (NVF) is notably high after vertebral augmentation (VA), but accurately assessing the imminent risk of NVF remains a great challenge. The aim of this study was to investigate whether the MRI-based vertebral bone quality (VBQ) score can predict the risk of imminent NVF after VA within a 2-year period. METHODS: A total of 135 patients age 50 years and older who suffered from painful osteoporotic vertebral compression fracture and treated with VA were enrolled in this retrospective study. Each patient's VBQ scores were calculated from T1-weighted, T2-weighted, and short tau inversion recovery sequences of preoperative lumbar MRI. The clinical factors and VBQ score were integrated to create a predictive model by using the logistic regression algorithm and visualize by nomogram. Receiver operating characteristic curve, calibration curve, and decision curve analyses were used to evaluate the predictive performance of the nomogram. RESULTS: The mean VBQ-T1WI and VBQ-T2WI scores of the NVF group were 4.61 ± 0.55 and 0.89 ± 0.14, respectively, which were significantly higher than those of the without NVF group (3.99 ± 0.54 and 0.79 ± 0.12, respectively, P < .001), as well as the VBQ-combined score (0.75 ± 1.30 vs -0.80 ± 1.26, P < .001), which is the combination of VBQ-T1WI and VBQ-T2WI scores. On multivariate analysis, the predictors of imminent NVF included age (odds ratio [OR] = 1.064, 95% CI = 1.009-1.122, P = .022), previous vertebral fracture (OR = 2.089, 95% CI = 0.888-4.915, P = .091), and VBQ-combined score (OR = 2.239, 95% CI = 1.529-3.279, P < .001). The nomogram achieved superior performance with an area under the receiver operating characteristic curve of 0.838 (95% CI: 0.773-0.904) in predicting the imminent NVF compared to the clinical factors or VBQ-combined score alone. CONCLUSION: The VBQ score obtained from lumbar MRI can be used to assess the VBQ and predict the imminent NVF after VA in patients with osteoporotic vertebral compression fracture.

Preoperative Prediction of New Vertebral Fractures after Vertebral Augmentation with a Radiomics Nomogram.

The occurrence of new vertebral fractures (NVFs) after vertebral augmentation (VA) procedures is common in patients with osteoporotic vertebral compression fractures (OVCFs), leading to painful experiences and financial burdens. We aim to develop a radiomics nomogram for the preoperative prediction of NVFs after VA. Data from center 1 (training set: n = 153; internal validation set: n = 66) and center 2 (external validation set: n = 44) were retrospectively collected. Radiomics features were extracted from MRI images and radiomics scores (radscores) were constructed for each level-specific vertebra based on least absolute shrinkage and selection operator (LASSO). The radiomics nomogram, integrating radiomics signature with presence of intravertebral cleft and number of previous vertebral fractures, was developed by multivariable logistic regression analysis. The predictive performance of the vertebrae was level-specific based on radscores and was generally superior to clinical variables. RadscoreL2 had the optimal discrimination (AUC ≥ 0.751). The nomogram provided good predictive performance (AUC ≥ 0.834), favorable calibration, and large clinical net benefits in each set. It was used successfully to categorize patients into high- or low-risk subgroups. As a noninvasive preoperative prediction tool, the MRI-based radiomics nomogram holds great promise for individualized prediction of NVFs following VA.

Rosavin: Research Advances in Extraction and Synthesis, Pharmacological Activities and Therapeutic Effects on Diseases of the Characteristic Active Ingredients of Rhodiola rosea L.

Rhodiola rosea L. (RRL) is a popular plant in traditional medicine, and Rosavin, a characteristic ingredient of RRL, is considered one of the most important active ingredients in it. In recent years, with deepening research on its pharmacological actions, the clinical application value and demand for Rosavin have been steadily increasing. Various routes for the extraction and all-chemical or biological synthesis of Rosavin have been gradually developed for the large-scale production and broad application of Rosavin. Pharmacological studies have demonstrated that Rosavin has a variety of biological activities, including antioxidant, lipid-lowering, analgesic, antiradiation, antitumor and immunomodulation effects. Rosavin showed significant therapeutic effects on a range of chronic diseases, including neurological, digestive, respiratory and bone-related disorders during in vitro and vivo experiments, demonstrating the great potential of Rosavin as a therapeutic drug for diseases. This paper gives a comprehensive and insightful overview of Rosavin, focusing on its extraction and synthesis, pharmacological activities, progress in disease-treatment research and formulation studies, providing a reference for the production and preparation, further clinical research and applications of Rosavin in the future.

Synthesis of fused 3-trifluoromethyl-1,2,4-triazoles via base-promoted [3 + 2] cycloaddition of nitrile imines and 1H-benzo[d]imidazole-2-thiols.

Here we report a strategy for the facile assembly of fused 3-trifluoromethyl-1,2,4-triazoles, which are difficult to synthesize using traditional strategies, in 50-96% yields through a triethylamine-promoted intermolecular [3 + 2] cycloaddition pathway. This protocol features high efficiency, good functional group tolerance, mild conditions, and easy operation. Furthermore, a gram-scale reaction and product derivatizations were carried out smoothly to illustrate the practicability of this method.

MRI-based radiomics assessment of the imminent new vertebral fracture after vertebral augmentation.

BACKGROUND: Imminent new vertebral fracture (NVF) is highly prevalent after vertebral augmentation (VA). An accurate assessment of the imminent risk of NVF could help to develop prompt treatment strategies. PURPOSE: To develop and validate predictive models that integrated the radiomic features and clinical risk factors based on machine learning algorithms to evaluate the imminent risk of NVF. MATERIALS AND METHODS: In this retrospective study, a total of 168 patients with painful osteoporotic vertebral compression fractures treated with VA were evaluated. Radiomic features of L1 vertebrae based on lumbar T2-weighted images were obtained. Univariate and LASSO-regression analyses were applied to select the optimal features and construct radiomic signature. The radiomic signature and clinical signature were integrated to develop a predictive model by using machine learning algorithms including LR, RF, SVM, and XGBoost. Receiver operating characteristic curve and calibration curve analyses were used to evaluate the predictive performance of the models. RESULTS: The radiomic-XGBoost model with the highest AUC of 0.93 of the training cohort and 0.9 of the test cohort among the machine learning algorithms. The combined-XGBoost model with the best performance with an AUC of 0.9 in the training cohort and 0.9 in the test cohort. The radiomic-XGBoost model and combined-XGBoost model achieved better performance to assess the imminent risk of NVF than that of the clinical risk factors alone (p < 0.05). CONCLUSION: Radiomic and machine learning modeling based on T2W images of preoperative lumbar MRI had an excellent ability to evaluate the imminent risk of NVF after VA.

Development and validation of a machine learning model to predict imminent new vertebral fractures after vertebral augmentation.

BACKGROUND: Accurately predicting the occurrence of imminent new vertebral fractures (NVFs) in patients with osteoporotic vertebral compression fractures (OVCFs) undergoing vertebral augmentation (VA) is challenging with yet no effective approach. This study aim to examine a machine learning model based on radiomics signature and clinical factors in predicting imminent new vertebral fractures after vertebral augmentation. METHODS: A total of 235 eligible patients with OVCFs who underwent VA procedures were recruited from two independent institutions and categorized into three groups, including training set (n = 138), internal validation set (n = 59), and external validation set (n = 38). In the training set, radiomics features were computationally retrieved from L1 or adjacent vertebral body (T12 or L2) on T1-w MRI images, and a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm (LASSO). Predictive radiomics signature and clinical factors were fitted into two final prediction models using the random survival forest (RSF) algorithm or COX proportional hazard (CPH) analysis. Independent internal and external validation sets were used to validate the prediction models. RESULTS: The two prediction models were integrated with radiomics signature and intravertebral cleft (IVC). The RSF model with C-indices of 0.763, 0.773, and 0.731 and time-dependent AUC (2 years) of 0.855, 0.907, and 0.839 (p < 0.001 for all) was found to be better predictive than the CPH model in training, internal and external validation sets. The RSF model provided better calibration, larger net benefits (determined by decision curve analysis), and lower prediction error (time-dependent brier score of 0.156, 0.151, and 0.146, respectively) than the CPH model. CONCLUSIONS: The integrated RSF model showed the potential to predict imminent NVFs following vertebral augmentation, which will aid in postoperative follow-up and treatment.

A review on the assembly of multi-substituted pyridines via Co-catalyzed [2 + 2 + 2] cycloaddition with nitriles.

In recent years, many methods for the facile synthesis of pyridines and their derivatives have been developed. The [2 + 2 + 2] cycloaddition reaction of alkynes and nitriles catalyzed by transition metals has emerged as the most straightforward and efficient method to obtain pyridine derivatives. Recently, Earth-abundant cobalt has been employed as a versatile and economical catalyst for the synthesis of functionalized molecules, as compared to other transition metals. This review mainly focuses on the recent research and development of the Co-catalyzed intramolecular [2 + 2 + 2] cycloaddition of diynes-nitriles or intermolecular [2 + 2 + 2] cycloaddition reaction of alkynes or diynes with nitriles for the construction of chiral or achiral multi-substituted pyridines. Meanwhile, brief mechanistic insights are also discussed here to explain the observed regioselectivity.

Quantitative magnetic resonance imaging assessment of brain injury after successful cardiopulmonary resuscitation in a rat model of asphyxia cardiac arrest.

The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DWI) to measure changes in blood-brain barrier (BBB) permeability and cerebral edema over time in a rat model of asphyxial cardiac arrest (ACA). ACA was established by endotracheal tube clamping. Male rats were randomized into a sham group (n = 5) and three ACA groups (n = 18). After return of spontaneous circulation (ROSC), the rats were randomized to perform DWI and DCE-MRI exam in the 6 h, 24 h and 72 h timepoint (ROSC + 6 h, ROSC + 24 h, and ROSC + 72 h). Results shows that fifteen of 18 animals achieved successful resuscitation in the ACA groups. The average apparent diffusion coefficient(ADC) value of the whole brain in ROSC + 6 h was markedly lower than those of the sham, ROSC + 24 h, and ROSC + 72 h. The aquaporin-4(AQP4) score in ROSC + 6 h was significantly higher than those in the other groups, which were negatively correlated with the ADC values. The ratio of whole brain to masseter muscle of volume transfer constant (rKtrans), tissue interstitium-to-plasma rate constant(rKep), and fractional extra-cellular space volume(rVe) in ROSC + 6 h were all significantly higher than those in the sham, ROSC + 24 h, and ROSC + 72 h. The transforming growth factor ß1(TGF-ß1) and vascular endothelial growth factor A(VEGF-a) scores in ROSC + 6 h were significantly higher than those in the other groups, which were all positively correlated with rKtrans and rKep. In conclusions, brain injury is a frequent complication after CA and resuscitation. DWI and DCE-MRI can quantitatively evaluate brain injury in term of cerebral edema and BBB permeability after successful CPR.

Investigation of a family cluster outbreak of COVID-19 indicates the necessity of CT screening for asymptomatic family members in close contact with confirmed patients.

BACKGROUND: To investigate whether asymptomatic close-contact family members of patients diagnosed with coronavirus disease (COVID-19) should immediately undergo CT screening in addition to the viral nucleic acid test. METHODS: We retrospectively analyzed the data of a family cluster of 8 individuals, of whom 1 family member (Patient 3) had an epidemiologic history of having visited Guangzhou from Hubei Province on January 20, 2020. Her father (Patient 1) developed a fever and respiratory system symptoms and was confirmed COVID-19-positive on February 4-5, 2020 at Zengcheng People's Hospital, Guangzhou, China. Seven close-contact family members of the patients were then screened for COVID-19 on February 5-6 at the hospital. The CT imaging manifestation and laboratory tests of this family cluster were investigated and reported. RESULTS: Five (62.5%) of the 8 family members were confirmed COVID-19-positive. Except for Patient 1, who had fever, cough, fatigue, and dizziness, the remaining four (4/5, 80%) COVID-19-positive family members (Patients 2-5) had no clinical symptoms. Among the 5 patients, 2 had leukopenia (2/5, 40%), 1 had low absolute neutrophil counts (1/5, 20%), and 2 had increased high-sensitivity C-reactive protein (2/5, 40%). Ground-glass opacity (GGO) was found on chest CT imaging in all 5 patients (5/5, 100%), with interlobular septal thickening. Thickened blood vessel shadows were seen in 3 patients (3/5, 60%). The 3 COVID-19-negative family members (Family Members 1-3) did not have CT abnormalities, and they showed negative reverse transcription-polymerase chain reaction (RT-PCR) results twice. CONCLUSIONS: CT screening is necessary in close-contact family members of a confirmed COVID-19 pneumonia case, regardless of the presence of clinical symptoms.

Enantioselective Assembly of Cycloenones with a Nitrile-Containing All-Carbon Quaternary Center from Malononitriles Enabled by Ni Catalysis.

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes, followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5-7-membered α-cyano-cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.

Erbium fractional laser irradiation combined with autologous platelet-rich plasma and platelet-poor plasma application for facial rejuvenation.

BACKGROUND: Erbium fractional laser treatment has immense skin rejuvenation effects, but it is associated with side effects such as erythema and pigmentation. Platelet-rich plasma (PRP) can enhance the restorative effects of Erbium fractional laser, but there are few studies on this combined treatment in the Asian population, and no study has examined the effects of adding platelet-poor plasma (PPP) to the combination. OBJECTIVE: This study aims to investigate the effects and safety of Erbium fractional laser irradiation combined with autologous PRP and PPP therapy for facial rejuvenation. METHODS: Between January 2010 and June 2016, 158 patients with facial skin aging were treated by Erbium fractional laser irradiation combined with autologous PRP and PPP. After three sessions, patients and experienced physicians evaluated the effectiveness of the treatment. RESULTS: The symptoms of skin aging, especially skin color, pore expansion, and skin texture, showed obvious improvement after the treatment, according to the evaluation of the patients and the physicians, who reported a total treatment effectiveness rate of 90.51% and 88.61%, respectively. The treatment was well-tolerated by all the participants, and no hyperpigmentation or depigmentation was observed in any of the cases. The reported side effects were edema (1-3 days), erythema (2-4 days), and crusting (3-10 days). CONCLUSION: Erbium fractional laser irradiation combined with PRP and PPP application is an effective and safe approach for improving facial skin aging and has minimal side effects. Future investigations on a bigger sample with a longer follow-up period should focus on optimizing the treatment protocol and settings.

Enantioselective Synthesis of ß-Quaternary Carbon-Containing Chromanes and 3,4-Dihydropyrans via Cu-Catalyzed Intramolecular C-O Bond Formation.

A copper-catalyzed efficient enantioselective construction of chiral quaternary carbon-containing chromanes and 3,4-dihydropyrans is reported. The desymmetric C-O coupling is enabled by a chiral dimethylcyclohexane-1,2-diamine ligand and provides the desired products in good yields with high enantioselectivities. This method presents a broad substrate scope and is applicable to diversely substituted aryl bromides and alkenyl bromides. The application is demonstrated by a gram-scale synthesis and derivatization of the products toward valuable building blocks.

Synthesis of polysubstituted pyridines from oxime acetates using NH4I as a dual-function promoter.

Pyridine formation with oxime acetates as the building blocks under metal-free conditions is described. Ammonium iodide has proved to be a highly efficient promoter for oxime N-O bond reduction and subsequent condensation reactions, whereby it played a dual-function role in the transformation. While the three-component reaction of oxime acetates, benzaldehydes, and 1,3-dicarbonyls proceeded well with the assistance of a stoichiometric amount of ammonium iodide, the condensation of oximes and acroleins was enabled by using a catalytic initiator to afford substituted pyridines. By this protocol, substituted pyridine products were generated in moderate to excellent yields with tolerance towards a broad range of functional groups.

Transition-Metal-Free N-O Reduction of Oximes: A Modular Synthesis of Fluorinated Pyridines.

An NH4I-based reductive system has been explored to promote the oxime N-O bond cleavage and thereby enable a modular synthesis of a broad range of pharmacologically significant fluorinated pyridines. Compared with traditional condensation methods for pyridine assembly, this protocol was found to be highly regio- and chemoselective and presented broad functional group tolerance.

A Three-Component Approach to 3,5-Diaryl-1,2,4-thiadiazoles under Transition-Metal-Free Conditions.

A novel route is disclosed for the synthesis of 1,2,4-thiadiazoles starting from amidines, elemental sulfur, and 2-methylquinolines or aldehydes under transition-metal-free conditions. This three-component approach affords efficient and rapid access to 3,5-diaryl substituted 1,2,4-thiadiazoles with good tolerance of a broad range of funcitional groups. Mechanistic studies reveal a radical-involved pathway.

O-Acyl oximes: versatile building blocks for N-heterocycle formation in recent transition metal catalysis.

O-Acyl oximes are versatile building blocks being widely applied in organic synthesis, especially for N-heterocycle construction under transition metal catalysis. In the last decade, aza-Heck cyclization using oximes has been progressing in the preparation of functionalized pyrrolines, and instead of Pd catalysis, copper-based catalytic systems were found to work well in some cases. O-Acyl oximes as oxidizing directing groups have attracted intensive attention in transition metal-mediated C-H activation reactions, which avoid the use of external oxidants to feature advantages including mild reaction conditions, higher levels of reactivities, chemo-selectivities, etc. Moreover, catalytic α C(sp(3))-H functionalization of O-acyl oximes and subsequent annulations provide a lot of opportunities for novel N-heterocycle synthesis. These transformations feature certain advantages: diversified and poly-functionalized products, mild and easy handling conditions, oximes serving as an internal oxidant to avoid the use of external oxidants, and so forth.

Metal-Free Assembly of Polysubstituted Pyridines from Oximes and Acroleins.

Transition-metal-catalyzed synthesis of N-heterocycles from oximes has been previously well established. In this paper, for the first time a metal-free protocol with the combinational employment of iodine and triethylamine has been demonstrated to be effective to trigger the oxime-based synthesis of pyridines with high chemo-selectivity and wide functional group tolerance. A broad range of functional pyridines were prepared in moderate to excellent yields. While neither iodine nor triethylamine could trigger this transformation, mechanistic experiments indicated a radical pathway for the reaction. The resultant 2-aryl-substituted pyridines have been proved to be versatile building blocks in a range of transition-metal-catalyzed C-H functionalization reactions.

Internal Oxidant-Triggered Aerobic Oxygenation and Cyclization of Indoles under Copper Catalysis.

A concise synthesis of pyrazolo[1,5-a]indole derivatives by copper-catalyzed aerobic oxygenation and cyclization of indoles with oxime acetates is described. This protocol represents an elegant example of N-1, C-2, and C-3 tri-functionalization of indoles in one-pot. Mechanistic studies indicate the reaction proceeds through a radical procedure. Oximes as an internal oxidant have been demonstrated to be a driver to initiate aerobic oxidation, which provides a new oxidative pattern for C-H functionalization even with high atom- and step-economy.

[Biomass Compositional Analysis Using Sparse Partial Least Squares Regression and Near Infrared Spectrum Technique].

Forest bio-fuel, a new type renewable energy, has attracted increasing attention as a promising alternative. In this study, a new method called Sparse Partial Least Squares Regression (SPLS) is used to construct the proximate analysis model to analyze the fuel characteristics of sawdust combining Near Infrared Spectrum Technique. Moisture, Ash, Volatile and Fixed Carbon percentage of 80 samples have been measured by traditional proximate analysis. Spectroscopic data were collected by Nicolet NIR spectrometer. After being filtered by wavelet transform, all of the samples are divided into training set and validation set according to sample category and producing area. SPLS, Principle Component Regression (PCR), Partial Least Squares Regression (PLS) and Least Absolute Shrinkage and Selection Operator (LASSO) are presented to construct prediction model. The result advocated that SPLS can select grouped wavelengths and improve the prediction performance. The absorption peaks of the Moisture is covered in the selected wavelengths, well other compositions have not been confirmed yet. In a word, SPLS can reduce the dimensionality of complex data sets and interpret the relationship between spectroscopic data and composition concentration, which will play an increasingly important role in the field of NIR application.