Cope Rearrangement of 1-Acyl-2-vinylcyclopropanes to Cyclohept-4-Enones.

Cycloheptenones are widespread in natural products and bioactive molecules. An efficient and convenient NaH-mediated Cope Rearrangement of doubly activated vinylcyclopropanes is reported for the synthesis of cyclohepten-4-ones. These flexible intramolecular reactions were applicable to a wide range of substrates and could be performed on gram scale. The derivatization of the product leads to short and highly efficient synthesis of some useful functional molecules.

Highly Efficient Visible-Blind Ultraviolet Photodetector Based on Scalably Produced Titanium Dioxide Nanowire Arrays.

Here, we report a novel, feasible, and cost-effective method for the preparation of one-dimensional TiO2 nanowire arrays using a super-aligned carbon nanotube film as a template. Pure-anatase-phase TiO2 nanowires were scalably prepared in a suspended manner, and a high-performance ultraviolet (UV) photodetector was realized on a flexible substrate. The large surface area and one-dimensional nanostructure of the TiO2 nanowire array led to a high detectivity (1.35 × 1016 Jones) and an ultrahigh photo gain (2.6 × 104), respectively. A high photoresponsivity of 7.7 × 103 A/W was achieved under 7 µW/cm2 UV (λ = 365 nm) illumination at a 10 V bias voltage, which is much higher than those of commercial UV photodetectors. Additionally, by taking advantage of its anisotropic geometry, we found the TiO2 nanowire array showed polarized photodetection. The concept of using nanomaterial systems shows the potential for realization of nanostructured photodetectors for practical applications.

Graphene Microheater Chips for In Situ TEM.

Low-dimensional materials are bringing significant innovations to in situ TEM characterization. Here a new graphene microheater chip for TEM was developed by stacking graphene on a suspended SiNx membrane as the Joule heating element. It could be heated up to 800 °C within 26.31 ms with a low power consumption of 0.025 mW/1000 µm2. The bulging was only ∼50 nm at 650 °C, which is 2 orders of magnitude smaller than those of conventional MEMS heaters at similar temperatures. The performances benefit from the employment of graphene, since its monolayer structure greatly reduces the heat capacity, and the vdW contact significantly reduces the interfacial interaction. The TEM observation on the Sn melting process verifies its great potential in resolving thermodynamic processes. Moreover, more multifunctional in situ chips could be developed by integrating other stimuli to such chips. This work opens a new frontier for both graphene and in situ characterization techniques.

Organocatalytic Cloke-Wilson Rearrangement: Carbocation-Initiated Tandem Ring Opening/Cyclization of Cyclopropanes under Neutral Conditions.

We report a metal-, acid-, and base-free 2-(bromomethyl)naphthalene (2-BMN)-promoted organocatalytic Cloke-Wilson rearrangement of chain doubly activated cyclopropanes for the construction of 2,3-dihydrofurans via a carbocation-initiated tandem intramolecular ring-opening/recyclization process. The strategy is especially suitable for the construction of furan units in complex molecules, providing a solution to the problem of heavy-metal residues in dihydrofuran-containing drugs synthesized by traditional metal-based protocols. Thus, it is of potential interest in synthetic and medicinal chemistry.

Anti-GPIb/IX autoantibodies are associated with poor response to dexamethasone combined with rituximab therapy in primary immune thrombocytopenia patients.

This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% vs. 47.6%, CR: 50.0% vs. 26.2%; P < 0.05) and 6 months (OR: 71.4% vs. 45.2%, CR: 42.9% vs. 25.0%; P < .05). Furthermore, patients with anti-GPIb/IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% vs. 78.3%; P < .05) and 6 months (OR: 29.2% vs. 78.3%; P < .05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, P = .003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients.

What is the context?The safety and efficacy of high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) are gradually recognized; however, there still needs to be an adequate clinical trial to predict its efficacy. Autoantibodies against platelet glycoproteins (GPs) are proven to be associated with a variety of therapeutic responses in ITP. Such as anti-GPIb/IX autoantibodies predict poor response to intravenous immunoglobulin G therapy and rhTPO therapy in ITP patients. Therefore, a retrospective study was needed to verify whether anti-GP autoantibodies can expect a response to DXM-RTX therapy in ITP patients.What is new?This study identified that anti-GPIb/IX autoantibodies were a predictive factor for poor response to DXM-RTX in ITP patients. It mainly manifested in the following aspects: (1) Overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at four weeks and six months. (2) Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies at both four weeks and six months were associated with the OR rate of patients.What is the impact?Our study suggests that ITP patients with anti-GPIb/IX positive autoantibodies respond poorly to DXM-RTX therapy. Platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX therapy in ITP patients.

Integrative Metabolome and Transcriptome Analyses Provide Insights into Carotenoid Variation in Different-Colored Peppers.

Carotenoids are important pigments in pepper fruits. The colors of each pepper are mainly determined by the composition and content of carotenoid. The 'ZY' variety, which has yellow fruit, is a natural mutant derived from a branch mutant of 'ZR' with different colors. ZY and ZR exhibit obvious differences in fruit color, but no other obvious differences in other traits. To investigate the main reasons for the formation of different colored pepper fruits, transcriptome and metabolome analyses were performed in three developmental stages (S1-S3) in two cultivars. The results revealed that these structural genes (PSY1, CRTISO, CCD1, CYP97C1, VDE1, CCS, NCED1 and NCED2) related to carotenoid biosynthesis were expressed differentially in the two cultivars. Capsanthin and capsorubin mainly accumulated in ZR and were almost non-existent in ZY. S2 is the fruit color-changing stage; this may be a critical period for the development of different color formation of ZY and ZR. A combination of transcriptome and metabolome analyses indicated that CCS, NCED2, AAO4, VDE1 and CYP97C1 genes were key to the differences in the total carotenoid content. These new insights into pepper fruit coloration may help to improve fruit breeding strategies.

Base-Promoted Intramolecular Addition of Vinyl Cyclopropanecarboxamides to Access Conformationally Restricted Aza[3.1.0]bicycles.

3-Azabicyclo[3.1.0]hexanes are common structural components in natural products and bioactive compounds. Traditionally, the metal-mediated cyclopropanation domino reaction of chain enzymes is the most commonly used strategy for the construction of this type of aza[3.1.0]bicycle derivative. In this study, a base-promoted intramolecular addition of alkenes used to deliver conformationally restricted highly substituted aza[3.1.0]bicycles is reported. This reaction was tailor-made for saturated aza[3.1.0] bicycle-containing fused bicyclic compounds that may be applied in the development of concise and divergent total syntheses of bioactive compounds.

Self-Powered Carbon Ink/Filter Paper Flexible Humidity Sensor Based on Moisture-Induced Voltage Generation.

Cellulose paper-based materials are highly flexible, hydrophilic, low-cost, and environmentally friendly and are good substrates for use as humidity sensors. Therefore, developing a paper-based humidity sensor with facile fabrication, low cost, and high sensitivity is important for expanding its practical applications. Herein, we propose a CI/FP self-powered humidity sensor based on everyday items such as writing and drawing carbon ink (CI), cellulose filter paper (FP), and polyester conductive adhesive tape, which is fabricated with the help of facile dip-coating and pasting methods. This sensor is self-powered, and the paper-based material itself can absorb water molecules in a humid environment to generate humidity-related voltage and current, which can indirectly reflect the ambient humidity level. They are characterized by a wide relative humidity (RH) sensing range (11-98%), good linearity (R2 = 0.97011), high response voltage (0.19 V), and excellent flexibility (over 1000 bends). This humidity sensor can be successfully applied to monitor human health (breathing, coughing), air humidity, and noncontact humidity sensing (skin, wet objects). This work not only proposes a low-cost and facile method for flexible humidity sensors but also provides a valuable strategy for the development of self-powered wearable electronics.

Rh(III)-Catalyzed Oxidative Domino C-H/N-H Annulation: Diarylureas as Arylamine Donors for the Assembly of Indolo[2,1-a]isoquinolines.

An efficient and convenient Rh(III)-catalyzed double aryl C(sp2)-H bond and N-H activation and annulation reaction is reported for the synthesis of indolo[2,1-a]isoquinolines in the presence of the Cu(OAc)2 oxidant under heating conditions. Distinct from previous works with other arylamine donors, one molecule of 1,3-diarylurea can serve as a precursor of two molecules of arylamine in the reaction with diaryl-substituted alkynes.

A case of hereditary hemorrhagic telangiectasia and literature review.

BACKGROUND: To discuss the clinical features of a patient with hereditary hemorrhagic telangiectasia (HHT). METHODS: The clinical data of one patient with HHT are retrospectively analysed. In addition, we review the relevant literature. RESULTS: A 32-year-old male patient was admitted to the hematology outpatient department of our hospital and presented with intermittent epistaxis for 24 years. In recent years, he was diagnosed with iron deficiency anemia. The nasal endoscopic examination showed telangiectasia at the front of the right-middle turbinate and the left nasal cavity. He had ENG genetic mutation positivity. CONCLUSIONS: Patients with HHT may suffer from many complications, including bleeding, anemia, iron deficiency, and high-output heart failure. These patients may have telangiectasias and arteriovenous malformations in various organs.

Inflammatory Mechanism of Brucella Infection in Placental Trophoblast Cells.

Brucellosis is a severe zoonotic infectious disease caused by the infection of the Brucella, which is widespread and causes considerable economic losses in underdeveloped areas. Brucella is a facultative intracellular bacteria whose main target cells for infection are macrophages, placental trophoblast cells and dendritic cells. The main clinical signs of Brucella infection in livestock are reproductive disorders and abortion. At present, the pathogenesis of placentitis or abortion caused by Brucella in livestock is not fully understood, and further research on the effect of Brucella on placental development is still necessary. This review will mainly introduce the research progress of Brucella infection of placental trophoblast cells as well as the inflammatory response caused by it, explaining the molecular regulation mechanism of Brucella leading to reproductive system disorders and abortion, and also to provide the scientific basis for revealing the pathogenesis and infection mechanism of Brucella.

The VirB System Plays a Crucial Role in Brucella Intracellular Infection.

Brucellosis is a highly prevalent zoonotic disease caused by Brucella. Brucella spp. are gram-negative facultative intracellular parasitic bacteria. Its intracellular survival and replication depend on a functional virB system, an operon encoded by VirB1-VirB12. Type IV secretion system (T4SS) encoded by the virB operon is an important virulence factor of Brucella. It can subvert cellular pathway and induce host immune response by secreting effectors, which promotes Brucella replication in host cells and induce persistent infection. Therefore, this paper summarizes the function and significance of the VirB system, focusing on the structure of the VirB system where VirB T4SS mediates biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV), the effectors of T4SS and the cellular pathways it subverts, which will help better understand the pathogenic mechanism of Brucella and provide new ideas for clinical vaccine research and development.

The Mechanism of Facultative Intracellular Parasitism of Brucella.

Brucellosis is a highly prevalent zoonotic disease characterized by abortion and reproductive dysfunction in pregnant animals. Although the mortality rate of Brucellosis is low, it is harmful to human health, and also seriously affects the development of animal husbandry, tourism and international trade. Brucellosis is caused by Brucella, which is a facultative intracellular parasitic bacteria. It mainly forms Brucella-containing vacuoles (BCV) in the host cell to avoid the combination with lysosome (Lys), so as to avoid the elimination of it by the host immune system. Brucella not only has the ability to resist the phagocytic bactericidal effect, but also can make the host cells form a microenvironment which is conducive to its survival, reproduction and replication, and survive in the host cells for a long time, which eventually leads to the formation of chronic persistent infection. Brucella can proliferate and replicate in cells, evade host immune response and induce persistent infection, which are difficult problems in the treatment and prevention of Brucellosis. Therefore, the paper provides a preliminary overview of the facultative intracellular parasitic and immune escape mechanisms of Brucella, which provides a theoretical basis for the later study on the pathogenesis of Brucella.

Correction to: The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma.

[This corrects the article DOI: 10.1186/s12935-019-0993-9.].

The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma.

BACKGROUND: To investigate the value of dynamic monitoring peripheral blood lymphocyte-to-monocyte (LMR) ratio in evaluating the treatment response and prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: A total of 148 patients with ENKTL were retrospectively analyzed in the Affiliated Tumor Hospital of Zhengzhou University between March 2012 and March 2018. The optimal cut-off value of LMR was determined using the receiver operating characteristic curve (ROC) method, then patients were divided into low LMR group and high LMR group. The LMR level was dynamically measured at various time points, and the relationships between LMR and therapeutic response, and survival were analyzed. RESULTS: The complete remission rate (CR) was 85.7% in patients with high LMR at diagnosis, which was remarkably higher than that of patients with low LMR at diagnosis (64.9%) (P = 0.009). The 5-year overall survival (OS) and progression-free survival (PFS) were 49.28% and 44.89% in the low LMR group, respectively; 5-year OS and PFS in the high LMR group were 84.50% and 67.12%, respectively, significantly longer (P values were < 0.001 and 0.034, respectively). The OS and PFS of patients with elevated LMR after treatment were longer than those with decreased LMR after treatment (all P values < 0.05). The LMRs at relapse were significantly lower in both high and low LMR groups than those of the last follow-up (P values were 0.001 and 0.016, respectively). Univariate and multivariate analysis demonstrated that low LMR was an independent risk factor for poor prognosis in ENKTL patients (P values were < 0.001 and 0.009, respectively). CONCLUSIONS: Lymphocyte to monocyte ratio can be used as an indicator of treatment response, prognosis and recurrence in patients with ENKTL. Low LMR before and after treatment is a poor prognostic factor.

Prostate Cancer Differentiation and Aggressiveness: Assessment With a Radiomic-Based Model vs. PI-RADS v2.

BACKGROUND: Multiparametric MRI (mp-MRI) combined with machine-aided approaches have shown high accuracy and sensitivity in prostate cancer (PCa) diagnosis. However, radiomics-based analysis has not been thoroughly compared with Prostate Imaging and Reporting and Data System version 2 (PI-RADS v2) scores. PURPOSE: To develop and validate a radiomics-based model for differentiating PCa and assessing its aggressiveness compared with PI-RADS v2 scores. STUDY TYPE: Retrospective. POPULATION: In all, 182 patients with biopsy-proven PCa and 199 patients with a biopsy-proven absence of cancer were enrolled in our study. FIELD STRENGTH/SEQUENCE: Conventional and diffusion-weighted MR images (b values = 0, 1000 sec/mm2 ) were acquired on a 3.0T MR scanner. ASSESSMENT: A total of 396 features and 385 features were extracted from apparent diffusion coefficient (ADC) images and T2 WI, respectively. A predictive model was constructed for differentiating PCa from non-PCa and high-grade from low-grade PCa. The diagnostic performance of each radiomics-based model was compared with that of the PI-RADS v2 scores. STATISTICAL TESTS: A radiomics-based predictive model was constructed by logistic regression analysis. 70% of the patients were assigned to the training group, and the remaining were assigned to the validation group. The diagnostic efficacy was analyzed with receiver operating characteristic (ROC) in both the training and validation groups. RESULTS: For PCa versus non-PCa, the validation model had an area under the ROC curve (AUC) of 0.985, 0.982, and 0.999 with T2 WI, ADC, and T2 WI&ADC features, respectively. For low-grade versus high-grade PCa, the validation model had an AUC of 0.865, 0.888, and 0.93 with T2 WI, ADC, and T2 WI&ADC features, respectively. PI-RADS v2 had an AUC of 0.867 in differentiating PCa from non-PCa and an AUC of 0.763 in differentiating high-grade from low-grade PCa. DATA CONCLUSION: Both the T2 WI- and ADC-based radiomics models showed high diagnostic efficacy and outperformed the PI-RADS v2 scores in distinguishing cancerous vs. noncancerous prostate tissue and high-grade vs. low-grade PCa. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:875-884.

Development of SNP, KASP, and SSR Markers by BSR-Seq Technology for Saturation of Genetic Linkage Map and Efficient Detection of Wheat Powdery Mildew Resistance Gene Pm61.

The gene Pm61 that confers powdery mildew resistance has been previously identified on chromosome arm 4AL in Chinese wheat landrace Xuxusanyuehuang (XXSYH). To facilitate the use of Pm61 in breeding practices, the bulked segregant analysis-RNA-Seq (BSR-Seq) analysis, in combination with the information on the Chinese Spring reference genome sequence, was performed in the F2:3 mapping population of XXSYH × Zhongzuo 9504. Two single nucleotide polymorphism (SNP), two Kompetitive Allele Specific PCR (KASP), and six simple sequence repeat (SSR) markers, together with previously identified polymorphic markers, saturated the genetic linkage map for Pm61, especially in the proximal side of the target gene that was short of gene-linked markers. In the newly established genetic linkage map, Pm61 was located in a 0.71 cM genetic interval and can be detected in a high throughput scale by the KASP markers Xicsk8 and Xicsk13 or by the standard PCR-based markers Xicscx497 and Xicsx538. The newly saturated genetic linkage map will be useful in molecular marker assisted-selection of Pm61 in breeding for disease resistant cultivar and in its map-based cloning.

Decoloration of waste PET alcoholysis liquid by an electrochemical method.

Disperse Red 60 simulated polyester alcoholysis liquid decoloration by electro-Fenton with Fe3O4 catalyst was studied. The influences of the main operating parameters such as catalyst dosage (0.3-0.9 g/L), current density (60-120 mA/cm2) and pH (1-7) were optimized by response surface methodology (RSM) based on Box-Behnken surface statistical design (BBD). In optimal conditions, the initial concentration of 25 mg/L disperse red polyester alcoholysis liquid was catalyzed by 0.6 g/L Fe3O4, and the decoloration efficiency was 97.18% with the current density of 90 mA/cm2 and initial pH of 4.6. There was a relative error of 1.18% with the predicted model when the predictive value was 98.25% under the same conditions. In addition, ultraviolet-visible absorption spectra (UV-Vis), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were used to study the degradation mechanism during decoloration. The intermediates were identified and the proposed degradation pathways were investigated by liquid chromatography-mass spectrometry (LC-MS) analysis.

Enhancing automatic prediction of clinically significant prostate cancer with deep transfer learning 2.5-dimensional segmentation on bi-parametric magnetic resonance imaging (bp-MRI).

Background: The aggressiveness of prostate cancer (PCa) is crucial in determining treatment method. The purpose of this study was to establish a 2.5-dimensional (2.5D) deep transfer learning (DTL) detection model for the automatic detection of clinically significant PCa (csPCa) based on bi-parametric magnetic resonance imaging (bp-MRI). Methods: A total of 231 patients, including 181 with csPCa and 50 with non-clinically significant PCa (non-csPCa), were enrolled. Stratified random sampling was then employed to divide all participants into a training set [185] and a test set [46]. The DTL model was obtained through image acquisition, image segmentation, and model construction. Finally, the diagnostic performance of the 2.5D and 2-dimensional (2D) models in predicting the aggressiveness of PCa was evaluated and compared using receiver operating characteristic (ROC) curves. Results: DTL models based on 2D and 2.5D segmentation were established and validated to assess the aggressiveness of PCa. The results demonstrated that the diagnostic efficiency of the DTL model based on 2.5D was superior to that of the 2D model, regardless of whether in a single or combined sequence. Particularly, the 2.5D combined model outperformed other models in differentiating csPCa from non-csPCa. The area under the curve (AUC) values for the 2.5D combined model in the training and test sets were 0.960 and 0.949, respectively. Furthermore, the T2-weighted imaging (T2WI) model showed superiority over the apparent diffusion coefficient (ADC) model, but was not as effective as the combined model, whether based on 2.5D or 2D. Conclusions: A DTL model based on 2.5D segmentation was developed to automatically evaluate PCa aggressiveness on bp-MRI, improving the diagnostic performance of the 2D model. The results indicated that the continuous information between adjacent layers can enhance the detection rate of lesions and reduce the misjudgment rate based on the DTL model.

Earlobe reconstruction with an inferior pedicle flap.

OBJECTIVE: This article describes an inferior pedicle flap for earlobe reconstruction. METHODS: The inferior pedicle flap was designed and marked according to the shape and size of the normal earlobe. The required flap was raised and folded to constitute a new earlobe and then sutured to the incised inferior edge of the earlobe defect. The donor site was directly closed. RESULTS: The reconstructed earlobe featured reliable vascularization and resulted in a natural appearance. No skin graft was needed for the donor site. The postoperative scars are short and concealed. CONCLUSIONS: The inferior pedicle flap is expected to provide a new idea for earlobe reconstruction.