We herein disclose a modular synthesis of 1-bromomethylene-THIQs involving a Catellani reaction of aryl iodides, aziridines, and terminal alkynes followed by an
N
-bromosuccinimide (NBS)-mediated ...cyclization. This approach features mild reaction conditions, wide substrate scope, good step-economy and good scalability. Based on this new method, we have accomplished the concise total synthesis of (±)-cularine, formal synthesis of 8-oxopseudopalmatine as well as the first total synthesis of dactyllactone A, demonstrating the wide synthetic potential of this method.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall's plaques (RPs) begin as interstitial calcium phosphate crystal ...deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation.
The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs.
experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA.
Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs.
validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis.
We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.
In the era of advanced precision medicine, next-generation genomic data are crucial to achieve breakthroughs in cancer medicine. Effective cancer mortality risk estimation for genomic data associated ...with cancer remains a vital challenge. The combination of machine learning algorithms and conventional survival analysis can advance the detection of high-risk missense mutation variants and candidate genes associated with cancer mortality in next-generation genomic data. In this article, a fuzzy logic system combined with machine learning algorithms and conventional survival analysis named FuzzyDeepCoxPH was proposed to identify high-risk missense mutation variants and candidate genes highly associated with cancer mortality. DL-derived abstracted weights and Cox proportional hazards (CoxPH) ratios were used to develop four model-based risk scores to consider the factor importance associated with risk stratification, time-varying effects, and individual and interaction effects among features. Fuzzy rules based on a fuzzy logic system were designed to integrate these considerations by merging four model-based risk scores to develop advanced risk estimation. The clinical features and next-generation sequencing of deoxyribonucleic acid and ribonucleic acid genomic data were used to evaluate FuzzyDeepCoxPH performance. The results indicated that FuzzyDeepCoxPH can effectively distinguish high-risk variants and candidate genes related to cancer mortality. In FuzzyDeepCoxPH, the fuzzy logic system was applied to combine DL-based and CoxPH-based models to provide a comprehensive cancer mortality risk estimation for cancer medicine.
(1) Background: Since early yield prediction is relevant for resource requirements of harvesting and marketing in the whole fruit industry, this paper presents a new approach of using image analysis ...and tree canopy features to predict early yield with artificial neural networks (ANN); (2) Methods: Two back propagation neural network (BPNN) models were developed for the early period after natural fruit drop in June and the ripening period, respectively. Within the same periods, images of apple cv. “Gala” trees were captured from an orchard near Bonn, Germany. Two sample sets were developed to train and test models; each set included 150 samples from the 2009 and 2010 growing season. For each sample (each canopy image), pixels were segmented into fruit, foliage, and background using image segmentation. The four features extracted from the data set for the canopy were: total cross-sectional area of fruits, fruit number, total cross-section area of small fruits, and cross-sectional area of foliage, and were used as inputs. With the actual weighted yield per tree as a target, BPNN was employed to learn their mutual relationship as a prerequisite to develop the prediction; (3) Results: For the developed BPNN model of the early period after June drop, correlation coefficients (R2) between the estimated and the actual weighted yield, mean forecast error (MFE), mean absolute percentage error (MAPE), and root mean square error (RMSE) were 0.81, −0.05, 10.7%, 2.34 kg/tree, respectively. For the model of the ripening period, these measures were 0.83, −0.03, 8.9%, 2.3 kg/tree, respectively. In 2011, the two previously developed models were used to predict apple yield. The RMSE and R2 values between the estimated and harvested apple yield were 2.6 kg/tree and 0.62 for the early period (small, green fruit) and improved near harvest (red, large fruit) to 2.5 kg/tree and 0.75 for a tree with ca. 18 kg yield per tree. For further method verification, the cv. “Pinova” apple trees were used as another variety in 2012 to develop the BPNN prediction model for the early period after June drop. The model was used in 2013, which gave similar results as those found with cv. “Gala”; (4) Conclusion: Overall, the results showed in this research that the proposed estimation models performed accurately using canopy and fruit features using image analysis algorithms.
Abstract
In this work, (Ba
0.97
Ca
0.03
)(Ti
0.96
Sn
0.005
Hf
0.035
)O
3
–0.03MnCO
3
–
x
LiF (BCTSH–0.03M–
x
L,
x
= 0–6 mol%) multilayer piezoelectric ceramics were prepared by the solid‐state ...synthesis technique. The microstructure and piezoelectric properties of the samples sintered at the reduced atmosphere and co‐fired with the Ni base metal inner electrode were studied. The results showed that 3 mol% LiF could effectively reduce the sintering temperature from 1350 to 1200°C. BCTSH–0.03M–3L ceramics exhibited excellent electrical properties with
d
33
= 277 pC/N,
d
31
= −132 pC/N,
k
p
= 0.350,
Q
m
= 315, and
ε
r
= 3387. Furthermore, the complex impedance spectroscopy (e.g., activation energy) was used to analyze the doping mechanism of these obtained ceramics sintered at reduced atmosphere. The results indicated when LiF was added in a small amount (
x
≤ 3), the bulk density was enhanced, and thus, the activation energy was also increased. Moreorver, when
x
> 3, Li ions could partly enter the interstitial site of crystal structure resulting in the increase of activation energy. Rayleigh behaviors of reversible and irreversible domain wall contributions were analyzed. It was observed when
x
= 3, there was a larger Rayleigh coefficient, suggesting that this sample had the weaker pinning effect, and thus contributing to the higher
d
33
value due to the irreversible domain wall contribution. As
x
> 3, the Rayleigh coefficient was found to decrease with increasing
x
due to the formation of the second phase, which could inhibit the motion of extrinsic domain wall. Finally, five‐layer multilayer piezoelectric ceramics co‐fired with inner Ni electrode were fabricated, and the electrical properties of five‐layer multilayer piezoelectric ceramics were found to be
d
33
= 1468 pC/N,
d
33
* = 2000 (at 20 kV/cm), and
k
p
= 0.342. To the best of our knowledge, the (Ba, Ca)(Ti, Sn, Hf)O
3
‐based lead‐free multilayer piezoelectric ceramics co‐fired with Ni‐based metal was first reported by us and used as the alternative multilayer ceramics for piezoelectric device applications.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Selenium (Se) is one of the potential candidates as photodetector because of its outstanding properties such as high photoconductivity (∼8 × 104 S cm–1), piezoelectricity, thermoelectricity, and ...nonlinear optical responses. Solution phase synthesis becomes an efficient way to produce Se, but a contamination issue that could deteriorate the electric characteristic of Se should be taken into account. In this work, a facile, controllable approach of synthesizing Se nanowires (NWs)/films via a plasma-assisted growth process was demonstrated at the low substrate temperature of 100 °C. The detailed formation mechanisms of nanowires arrays to thin films at different plasma powers were investigated. Moreover, indium (In) layer was used to enhance the adhesive strength with 50% improvement on a SiO2/Si substrate by mechanical interlocking and surface alloying between Se and In layers, indicating great tolerance for mechanical stress for future wearable devices applications. Furthermore, the direct growth of Se NWs/films on a poly(ethylene terephthalate) substrate was demonstrated, exhibiting a visible to broad infrared detection ranges from 405 to 1555 nm with a high on/off ratio of ∼700 as well as the fast response time less than 25 ms. In addition, the devices exhibited fascinating stability in the atmosphere over one month.
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IJS, KILJ, NUK, PNG, UL, UM
The combination of least square support vector machine (LS-SVM) and cuckoo search (CS) algorithm was first proposed to identify the dynamic models of unmanned surface vehicle (USV). The 3-DOF of ...Abkowitz model was selected to describe the USV's dynamics. The zigzag test was carried out in the Qinghuai river. The input data and output data obtained by the experiment were selected and filtered to identify the USV's dynamics. The back propagation neural network (BPNN) is a popular method to identify the ship dynamics and was adopted, in this paper, to compare the LSSVM. In addition, the frequently optimization algorithm including particle swarm optimization (PSO) and cross validation (CV) were also selected to enhance the LSSVM which compare to the CS-LSSVM. The results showed that the CS-LSSVM had a better predictive capability than the BPNN, PSO-LSSVM and CV-LSSVM in predicting the surge velocity and sway velocity and the values were close to the experimental data. The related mean square errors of CS-LSSVM was the lowest in these methods and has the fastest convergence speed. It can be tested that CS-LSSVM would be a potential method to online parameter identification for USV in the future.
•The experiments of USV is carried out in the real environment.•The Abkowitz models were selected to describe the USV’s dynamic models.•CS-LSSVM has a stronger robust in system identification of USV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recently, drug resistance due to the extensive abuse and over-use of antibiotics has become an increasingly serious problem, making the development of alternative antibiotics a very urgent issue. In ...this study, the Chinese herbal medicine, Polygonum cuspidatum, was extracted with 95% ethanol and the crude extracts were further purified by partition based on solvent polarity. The antimicrobial activities of the extracts and fractions were determined by the disk diffusion and minimum inhibitory concentration (MIC) methods. The results showed that the ethyl ether fraction (EE) of the ethanol extracts possesses a broader antimicrobial spectrum and greater antimicrobial activity against all of the tested clinical drug-resistant isolates, with a range of MIC values between 0.1-3.5 mg/mL. The active extract showed complete inhibition of pathogen growth and did not induce resistance to the active components. In addition, according to scanning electron microscope observations, EE resulted in greater cell morphological changes by degrading and disrupting the cell wall and cytoplasmic membrane, whereby ultimately this cell membrane integrity damage led to cell death. In conclusion, the EE extracts from Polygonum cuspidatum may provide a promising antimicrobial agent for therapeutic applications against nosocomial drug-resistant bacteria.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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