Radical Decarboxylation-Initiated SH2' Reaction of ß,ß-Difluoroenol Sulfonates: Access to α,α-Difluoroketones.

Reported herein is a novel radical decarboxylation-initiated SH2' reaction of ß,ß-difluoroenol sulfonates. This transformation is characterized by mild reaction conditions, a broad substrate scope, and late-stage modification of drug molecules, providing general and mechanistically distinct access to bioactive and synthetically versatile α,α-difluoroketones. Preliminary mechanistic studies demonstrate that this reaction proceeds through a succession of silver-mediated decarboxylative radical generation and radical-addition-induced ß-elimination of the sulfonyl radical.

Microstructure and Properties of Pressureless-Sintered Zirconium Carbide Ceramics with MoSi2 Addition.

Zirconium carbide (ZrC) ceramics have a high melting point, low neutron absorption cross section, and excellent resistance to the impact of fission products and are considered to be one of the best candidate materials for fourth-generation nuclear energy systems. ZrC ceramics with a high relative density of 99.1% were successfully prepared via pressureless sintering using a small amount of MoSi2 as an additive. The influence of the MoSi2 content on the densification behavior, microstructure, mechanical properties, and thermal properties of ZrC ceramics was systematically investigated. The results show that the densification of ZrC was significantly enhanced by the introduction of MoSi2 due to the formation of a liquid phase during sintering. In addition, the ZrC grains were refined due to the pinning effect of the generated silicon carbide. The flexural strength and Vickers hardness of ZrC ceramics with 2.5 vol% MoSi2 sintered at 1850 °C were 408 ± 12 MPa and 17.1 GPa, respectively, which were approximately 30% and 10% higher compared to the samples without the addition of MoSi2. The improved mechanical properties were mainly attributed to the high relative density (99.1%) and refined microstructure.

Effect of Ti Doping on the Microstructure and Properties of SiCp/Al Composites by Pressureless Infiltration.

The effects of Ti doping on the microstructure and properties of SiCp/Al composites fabricated by pressureless infiltration were comprehensively investigated using first-principles calculations and experimental analyses. First-principles calculations revealed that the interface wetting and bonding strength in an Al/SiC system could be significantly enhanced by Ti doping. Subsequently, the Ti element was incorporated into SiC preforms in the form of TiO2 and TiC to verify the influence of Ti doping on the pressureless infiltration performance of SiCp/Al composites. The experimental results demonstrated that the pressureless infiltration of molten Al into SiC preforms was promoted by adding TiC or TiO2 due to the improved wettability. However, incorporating TiO2 leads to the growth of AlN whiskers under a N2 atmosphere, thereby hindering the complete densification of the composites. On the other hand, TiC doping can improve wettability and interface strength without deleterious reactions. As a consequence, the TiC-doped SiCp/Al composites exhibited excellent properties, including a high relative density of 99.4%, a bending strength of 287 ± 18 MPa, and a thermal conductivity of 142 W·m-1·K-1.

PLGA-PEG-PLGA hydrogel with NEP1-40 promotes the functional recovery of brachial plexus root avulsion in adult rats.

Adult brachial plexus root avulsion can cause serious damage to nerve tissue and impair axonal regeneration, making the recovery of nerve function difficult. Nogo-A extracellular peptide residues 1-40 (NEP1-40) promote axonal regeneration by inhibiting the Nogo-66 receptor (NgR1), and poly (D, L-lactide-co-glycolide)-poly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel can be used to fill in tissue defects and concurrently function to sustain the release of NEP1-40. In this study, we established an adult rat model of brachial plexus nerve root avulsion injury and conducted nerve root replantation. PLGA-PEG-PLGA hydrogel combined with NEP1-40 was used to promote nerve regeneration and functional recovery in this rat model. Our results demonstrated that functional recovery was enhanced, and the survival rate of spinal anterior horn motoneurons was higher in rats that received a combination of PLGA-PEG-PLGA hydrogel and NEP1-40 than in those receiving other treatments. The combined therapy also significantly increased the number of fluorescent retrogradely labeled neurons, muscle fiber diameter, and motor endplate area of the biceps brachii. In conclusion, this study demonstrates that the effects of PLGA-PEG-PLGA hydrogel combined with NEP1-40 are superior to those of other therapies used to treat brachial plexus nerve root avulsion injury. Therefore, future studies should investigate the potential of PLGA-PEG-PLGA hydrogel as a primary treatment for brachial plexus root avulsion.

Palladium-Catalyzed Electrophilic Functionalization of Pyridine Derivatives through Phosphonium Salts.

Herein, we report a highly efficient and practical method for pyridine-derived heterobiaryl synthesis through palladium-catalyzed electrophilic functionalization of easily available pyridine-derived quaternary phosphonium salts. The nice generality of this reaction was goes beyond arylation, enabling facile incorporation of diverse carbon-based fragments, including alkenyl, alkynyl, and also allyl fragments, onto the pyridine core. Notably, the silver salt additive is revealed to be of vital importance for the success of this transformation and its pivotal role as transmetallation mediator, which guarantees a smooth transfer of pyridyl group to palladium intermediate, is also described.

Deep scaled dot-product attention based domain adaptation model for biomedical question answering.

Biomedical text mining is becoming increasingly important as the number of biomedical documents grow rapidly. Deep learning has boosted the development of biomedical text mining models. However, as deep learning models require a large amount of training data, a hierarchical attention based transfer learning model is proposed in this paper for the question answering task in biomedical field which lacks of sufficient training data. We adopt BERT (Bidirectional Encoder Representation Transformers), which has the ability to learn from large-scale unsupervised data, to enrich the semantic representation in our model. Especially, the scaled dot-product attention mechanism captures the question interaction clues for passage encoding. The domain adaptation technique of fine-tuning is used to reinforce the performance, which penalizes the deviations from the source model's parameters and remembers the knowledge of source domain. We evaluate the system performance on the open data set of BioASQ-Task B. The results show that our system achieves the state-of-the-art performance without any handcrafted features and outperforms the best solution for factoid questions in 2016 and 2017 BioASQ-Task B.

Hoveyda-Grubbs II Catalyst: A Useful Catalyst for One-Pot Visible-Light-Promoted Ring Contraction and Olefin Metathesis Reactions.

A one-pot reaction to synthesize functionalized 2 H-azirines through visible-light-mediated ring contraction and olefin metathesis of isoxazoles is described. Hoveyda-Grubbs II catalyst was found to function as a photocatalyst for these transformations, allowing these processes to be carried out in a one-pot manner. This study offers a new entry for the application of Grubbs catalysts as efficient photocatalysts and the possibilities of carrying out other photoreactions and olefin metathesis in a one-pot process.

[Activity of factor VII in patients with isolated blunt traumatic brain injury: association with coagulopathy and progressive hemorrhagic injury].

OBJECTIVE: To explore the relationship of the activity of plasma FVII with isolated blunt traumatic brain injury and progressive hemorrhagic injury. METHODS: Eight-one isolated traumatic brain patients with moderate-to-severe injury, aged ≥ 16 yrs, were recruited from August 2010 to December 2012. The plasma factor VII activity was measured after admission. On arrival at emergency department, blood samples were collected to analyze the parameters of activated partial thromboplastic time (aPTT), international normalized ratio (INR), platelet count and activity of factor VII. TBI-associated coagulopathy was defined as elevated international normalized ratio >1.2 or prolonged activated partial thromboplastic time >40 seconds or platelet count <120×10(9)/L at admission. Progressive hemorrhagic injury was present when follow-up computed tomography (CT) noted any increase in size or number of hemorrhagic lesions. Logistic regression examined the risks for coagulopathy and progressive hemorrhagic injury after isolated traumatic brain injury. RESULTS: FVII activity in patients with coagulopathy was 86% ± 35%. And it was significantly lower than those without coagulopathy (100 ± 29%, P < 0.05). Isolated traumatic brain injury patients with FVII activity <77.5% had an odds ratio for coagulopathy of 5.52 (95% confidence interval 1.82-16.68, P < 0.05) relative to those with FVII activity ≥ 77.5%. FVII activity in patients with progressive hemorrhagic injury was 71% ± 18%. And it was significantly lower than those without progressive hemorrhagic injury (106% ± 32%, P < 0.001). Stepwise Logistic regression analysis identified FVII < 77.5% as a predisposing risk factor independently associated with the presence of progressive hemorrhagic injury. The overall mortality rate in the surveyed population was 7.4% (6/81). The plasma FVII in deceased patients (91% ± 47%) was slightly lower than that in survivors (92% ± 32%, P > 0.05). No significant difference existed between two groups (P > 0.05). CONCLUSIONS: Decreased activity of FVII is closely correlated with coagulopathy in patients with isolated blunt traumatic brain injury. And coagulopathy and decreased FVII activity are predisposing risk factors independently associated with progressive hemorrhagic injury.

Activity of factor VII in patients with isolated blunt traumatic brain injury: association with coagulopathy and progressive hemorrhagic injury.

BACKGROUND: Given the importance of factor VII (FVII) in extrinsic pathway of coagulation cascade, we sought to elucidate the relationship between FVII and traumatic brain injury-induced coagulopathy and progressive hemorrhagic injury (PHI). METHODS: Eighty-one patients with isolated traumatic brain injury, 16 years or older, were recruited between 2010 and 2012. Blood was collected on arrival in the emergency department and analyzed with activated partial thromboplastic time, international normalized ratio, platelet count, and activity of FVII. Coagulopathy was defined as thrombocytopenia (platelet count < 120,000/µL) or elevated international normalized ratio of greater than 1.2 or prolonged activated partial thromboplastin time greater than 40 seconds at admission. PHI was present when the follow-up computed tomographic scan reported any increase in size or number of the hemorrhagic lesions. Logistic regression examined the risks for coagulopathy and PHI. RESULTS: Mean (SD) FVII activity in patients with coagulopathy was 85.69% (34.88%), which was significantly lower than patients without coagulopathy (99.57% [29.37%], p = 0.04). Isolated traumatic brain injury patients with FVII activity less than 77.5% have an odds ratio for coagulopathy of 5.52 (95% confidence interval, 1.82-16.68; p = 0.03) relative to patients with FVII activity of 77.5% or greater. Mean (SD) FVII activity in patients with PHI was 70.76% (18.21%), which was significantly lower than patients without PHI (105.76% [32.27%], p < 0.001). A stepwise logistic regression analysis identified FVII less than 77.5% (odds ratio, 4.53; 95% confidence interval, 1.62-12.67; p = 0.004) as a predisposing risk factors independently associated with the presence of PHI. The overall mortality rate in the study population was 7.4% (n = 6). The plasma FVII in death patients (91.44% [47.19%]) was slightly lower than that in survival patients (92.01% [32.04%]). However, there was no statistical difference between the two groups (p = 0.95). CONCLUSION: A decrease of FVII activity significantly contributes to the coagulopathy and PHI in patients with isolated traumatic brain injury. LEVEL OF EVIDENCE: Prognostic study, level III.

[Role of small-dose recombinant human coagulation factor VIIa for coagulopathy in patients with isolated traumatic brain injury].

OBJECTIVE: To explore the role of small-dose recombinant human coagulation factor VIIa (rFVIIa) for coagulopathy in patients with isolated traumatic brain injury. METHODS: A total of 86 isolated traumatic brain patients with coagulopathy were treated at our neurosurgery intensive care unit (NICU) from January 2010 to December 2012. Their trauma registry data included mortality, pre-and post-rFVIIa coagulation parameters. Two-tailed paired t-test was used to determine significant changes in coagulation parameters and other major clinical parameters. RESULTS: Twenty-seven patients made up the low-dose rFVIIa (20 µg/kg) group. And the control group had 59 well-matched subjects. At admission, age, blood pressure, Glasgow coma scale score, hemoglobin, platelets and international normalize ratio were similar in both groups. After treatment, the INR of patients on rFVIIa was lower than that of the conventional treatment group (1.1 ± 0.2 vs 1.2 ± 0.2, P < 0.01) and it declined more in the rFVIIa group (0.3 ± 0.2 vs 0.1 ± 0.4, P = 0.05). No significant difference existed in mortality or length of stay between two groups.There was no occurrence of subsequent thromboembolic events. CONCLUSION: The application of small-dose rFVIIa can effectively reduce the value of INR and improve the coagulation status of patients. During the course of treatment, no major adverse events occur.