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Adiponitrile, as an important bulk chemical, was synthesized in two steps: catalytic amination of ε-caprolactone to 6-hydroxyhexanenitrile over a ZnO catalyst through a patented process, followed by catalytic amination of 6-hydroxyhexanenitrile to adiponitrile. An Al2O3-MgO composite-supported bimetallic catalyst Ni30Fe10/Al2O3-MgO(0.8:1.2)-700-2 was found to be efficient in the catalytic amination of 6-hydroxyhexanenitrile to adiponitrile. Under the optimal reaction conditions, which are a reaction temperature of 300 °C, atmospheric pressure, 6-hydroxyhexanenitrile/NH3/H2molar ratios of 1:5:2, and a residence time of 5 s, the conversion of 6-hydroxyhexanenitrile reached 63.1% with an adiponitrile selectivity of 51.5%, corresponding to a one-pass adiponitrile yield of 32.5%. The characterization results revealed that Ni and Fe are present in the form of Ni3Fe alloy nanoparticles with diameters of 8 to 16 nm in the catalyst Ni30Fe10/Al2O3-MgO(0.8:1.2)-700-2. The good catalysis of Ni30Fe10/Al2O3-MgO(0.8:1.2)-700-2 could be ascribed to the synergetic effect between the two metals in the Ni3Fe alloy and a suitable magnesium-to-aluminum molar ratio in the catalyst. Catalyst deactivation took place due to the deposition of carbonaceous substances on the surface of the catalyst in a catalytic run, and the deactivated catalyst could be regenerated fully by high-temperature reduction with H2.

The rationale for ethnic differences in bladder cancer (BCa) susceptibility is an important open question. In this study, we raised the hypothesis that the APOBEC3-rs1014971 variant associated with BCa risk and APOBEC-mutagenesis probably contribute to ethnic differences. We calculated the ethnicity-stratified 5-year age-adjusted incidence rates of BCa using the US SEER database. We performed somatic mutational-signature analyses and compared the APOBEC-related mutational contribution across BCa tumors in patients of different ethnicities. We analyzed the allele frequency distribution of APOBEC3-related rs1014971 in contemporary populations of different ethnicities and in ancient human genomes. We also analyzed the natural selection profiles and ages of the investigated SNPs. We validated the ethnic difference in BCa risk using US SEER data, revealing Caucasians to be at >2-fold greater risk than Asians / Pacific islanders. In contemporary populations, we observed a coherent ethnic distribution in terms not only of the allele frequency of APOBEC3-related rs1014971, but also the mutational contribution of APOBEC-mediated mutagenesis in BCa tumors. Population genetics and ancient genome analyses further suggested that the diverse ethnic distribution of rs1014971 could be rooted in human evolution. It is possible that APOBEC3-related rs1014971 is involved in the different BCa incidence across ethnic groups, and this difference is potentially derived from human evolution. Our findings suggested an evolutionary link between contemporary population-level variations in malignancy susceptibility and pathogen-driven selection in the past, not unlike previously reported cases of certain autoimmune and metabolic disorders.

An elegant Pd-catalyzed intramolecular Heck dearomative alkenylation of aryl iodides with functionalized N-tosylhydrazones proceeded through a sequential dearomative carbopalladation, migratory insertion, and β-hydride elimination in the presence of Pd(CF3COO)2(10 mol %), PPh3(30 mol %), and Cs2CO3(2.0 equiv) in 1,4-dioxane (2.0 mL) at 120 °C for 14 h under an argon atmosphere. This cascade cycloaddition protocol provided a reliable and versatile approach to a sequence of structurally diverse indolines in moderate to good yields with good functional group compatibility. In addition, the synthetic robustness of the methodology is highlighted by a scaled-up experiment and derivatization of products via epoxidation and reduction reactions.

A facile and efficient method for the synthesis of primary phosphinamides from Ar2P(O)–H reagents with stable and readily available ammonium carbonate as an ammonia source is disclosed herein for the first time. This ethyl bromoacetate-mediated primary amination proceeds smoothly under mild and simple conditions, without any metal catalyst or oxidant. Moreover, this method is also appropriate for the reaction of Ar2P(O)–H with a variety of amines, alcohols, and phenols to construct P–N or P–O bonds, with features of handy operation, good functional group tolerance, and broad substrate scope.

Background: Connecting genes to phenotypes is still a great challenge in genetics. Research related to gene-phenotype associations has made remarkable progress recently due to high-throughput sequencing technology and genome-wide association study (GWAS). However, these genes, which are considered to be significantly associated with a target phenotype according to traditional GWAS, are less precise or subject to greater confounding. Objective: The present study is an attempt to prioritize functional genes for complex phenotypes employing protein-protein interaction (PPI) network-based systems genetics methods on available GWAS results. Methods: In this paper, we calculated the functional gene enrichment ratios of the trait ontology of A. thaliana for three common systems genetics methods (i.e. GeneRank, K-shell and HotNet2). Then, comparison of gene enrichment ratios obtained by PPI network-based methods was performed. Finally, a hybrid model was proposed, integrating GeneRank, comprehensive score algorithm and HotNet diffusion- oriented subnetworks (HotNet2) to prioritize functional genes. Results: These PPI network-based systems genetics methods were indeed useful for prioritizing 775henoltype-associated genes. And functional gene enrichment ratios calculated from the top 20% of GeneRank-identified genes were higher than these ratios of K-shell and these ratios of HotNet2 for most phenotypes. However, the hybrid model can improve the efficiency of functional gene enrichment for A. thaliana (up to 40%). Conclusion: The present study provides a hybrid method integrating GeneRank, comprehensive score algorithm and HotNet2 to prioritize functional genes. The method will contribute to functional genomics in plants. The source data and codes are freely available at http://47.242.161.60/Plant/.

Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin−) cells. PBMCs and Lin−cells were cocultured with induced pluripotent stem cell‐derived MSCs (iPSC‐MSCs) under the stimulation of epithelial cytokines IL‐25 and IL‐33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS‐ICOSL pathway. iPSC‐MSCs successfully decreased the high levels of IL‐13, IL‐9, and IL‐5 in PBMCs in response to IL‐25, IL‐33, and the high percentages of IL‐13+ILC2s and IL‐9+ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC‐MSCs. However, iPSC‐MSCs were found directly to enhance ILC2 levels and functions via ICOS‐ICOSL interaction in Lin−cells and pure ILC2s. iPSC‐MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS‐ICOSL interaction. The MSC‐induced Treg cells then suppressed ILC2s by secreting IL‐10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS‐ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders. Human mesenchymal stem cells (MSCs) either directly promote group 2 innate lymphoid cell (ILC2) activation through upregulated ICOS‐ICOSL interaction. MSCs exert inhibitory effects on ILC2s via activating regulatory T (Treg) cells through ICOS‐ICOSL interaction. Treg cells prevent the promotion of MSCs on ILC2s via decreased ICOS‐ICOSL interaction between MSCs and ILC2s. IL‐10 is required for the MSC‐induced Treg cells in suppressing ILC2s alongside ICOS‐ICOSL interaction.

Both recent studies and our calculation suggest that the physicochemical properties of launched drugs changed continuously over the past decades. Besides shifting of commonly used properties, the average biological relevance (BR) and similarity to natural products (NPs) of launched drugs decreased, reflecting the fact that current drug discovery deviated away from NPs. To change the current situation characterized by high investment but low productivity in drug discovery, efforts should be made to improve the BR of the screening library and hunt drugs more effectively in the biologically relevant chemical space. Additionally, a multiple dimensional molecular descriptor, named the biologically relevant spectrum (BRS) was proposed for quantitative structure–activity relationships (QSAR) study or screening library preparation. Prediction models for 43 biological activity categories were developed with BRS and support vector machine (SVM). In most cases, the overall prediction accuracies were around 95% and the Matthew’s correlation coefficients (MCC) were over 0.8. Thirty-seven out of 48 drug-activity associations were successfully predicted for drugs that launched from 2006 to 2012, which were not included in the training data set. A web-server named BioRel (http://ibi.hzau.edu.cn/biorel) was developed to provide services including BR, BRS calculation, activity class, and pharmacokinetic property prediction.

Microgravity in the space environment can potentially have various negative effects on the human body, one of which is bone loss. Given the increasing frequency of human space activities, there is an urgent need to identify effective anti-osteoporosis drugs for the microgravity environment. Traditional microgravity experiments conducted in space suffer from limitations such as time-consuming procedures, high costs, and small sample sizes. In recent years, the in-silico drug discovery method has emerged as a promising strategy due to the advancements in bioinformatics and computer technology. In this study, we first collected a total of 184,915 literature articles related to microgravity and bone loss. We employed a combination of dependency path extraction and clustering techniques to extract data from the text. Afterwards, we conducted data cleaning and standardization to integrate data from several sources, including The Global Network of Biomedical Relationships (GNBR), Curated Drug-Drug Interactions Database (DDInter), Search Tool for Interacting Chemicals (STITCH), DrugBank, and Traditional Chinese Medicines Integrated Database (TCMID). Through this integration process, we constructed the Microgravity Biology Knowledge Graph (MBKG) consisting of 134,796 biological entities and 3,395,273 triplets. Subsequently, the TransE model was utilized to perform knowledge graph embedding. By calculating the distances between entities in the model space, the model successfully predicted potential drugs for treating osteoporosis and microgravity-induced bone loss. The results indicate that out of the top 10 ranked western medicines, 7 have been approved for the treatment of osteoporosis. Additionally, among the top 10 ranked traditional Chinese medicines, 5 have scientific literature supporting their effectiveness in treating bone loss. Among the top 20 predicted medicines for microgravity-induced bone loss, 15 have been studied in microgravity or simulated microgravity environments, while the remaining 5 are also applicable for treating osteoporosis. This research highlights the potential application of MBKG in the field of space drug discovery.

5-Methyltetrahydrofolate (5-MTHF) is an active form of folic acid (FA) and an essential micronutrient preventing anemia and numerous other adverse health conditions such as cardiovascular disease and cancer. Herein, a continuous flow sequence synthesis of 5-MTHF from FA was developed, involving three elementary steps: catalytic hydrogenation of FA to tetrahydrofolic acid (THFA), methylenation of THFA with formaldehyde, and hydrogenation of the methylenation intermediates to 5-MTHF. This process features an expeditious synthesis of 5-MTHF in an integrated flow platform with water as the sole solvent and without any intermediate purification. The overall yield of this three-step flow process was up to 53.54% in a total residence time of 71.4 min. The separated yield of 5-MTHF reached 49.3%.

Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg−1·d−1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.

In this paper, we have disclosed efficient room-temperature phosphorescence (RTP) in the amorphous state from a triarylborane-based biphenyl derivative, 4,4′-dibromo-2-dimesitylboryl-2′-(N,N-dimethylamino)biphenyl (Br2-BN-BPh). The phosphorescence quantum yields of vigorously ground powder and drop-cast film are 0.36 and 0.22, respectively. Owing to the presence of two bulky substituents at the lateral positions, the existence of the intramolecular π–π interaction and the B···N electronic interaction, this compound is intramolecularly rigid, which is helpful to retard the vibrational motions and thus suppress the nonradiative decay in the solid state. In addition, this compound has a very small ΔES-Tdue to the well separation of HOMO and LUMO as a result of the significant twisting of the biphenyl skeleton. The combination of the small ΔES-Tand heavy atom effect of the bromo substituent is expected to enhance the spin–orbital coupling and thus increase intersystem crossing. Consequently, both the steric and electronic effects of the dimesitylboryl group are important for the efficient RTP property of Br2-BN-BPh, especially in the amorphous state.

Infection is one of the primary causes of death from immune thrombocytopenia (ITP), and the lungs are the most common site of infection. We identified the factors associated with hospitalization for community-acquired pneumonia (CAP) in nonsplenectomized adults with ITP and established the ACPA prediction model to predict the incidence of hospitalization for CAP. This was a retrospective study of nonsplenectomized adult patients with ITP from 10 large medical centers in China. The derivation cohort included 145 ITP inpatients with CAP and 1360 inpatients without CAP from 5 medical centers, and the validation cohort included the remaining 63 ITP inpatients with CAP and 526 inpatients without CAP from the other 5 centers. The 4-item ACPA model, which included age, Charlson Comorbidity Index score, initial platelet count, and initial absolute lymphocyte count, was established by multivariable analysis of the derivation cohort. Internal and external validation were conducted to assess the performance of the model. The ACPA model had an area under the curve of 0.853 (95% confidence interval [CI], 0.818-0.889) in the derivation cohort and 0.862 (95% CI, 0.807-0.916) in the validation cohort, which indicated the good discrimination power of the model. Calibration plots showed high agreement between the estimated and observed probabilities. Decision curve analysis indicated that ITP patients could benefit from the clinical application of the ACPA model. To summarize, the ACPA model was developed and validated to predict the occurrence of hospitalization for CAP, which might help identify ITP patients with a high risk of hospitalization for CAP.

China is an important domestication center of yams, and two main yam species of Dioscorea oppositaand D. alataare commonly cultivated in China. However, the differences of nutritional and medicinal characteristics between the two species and their subgroups remain unclear, which would greatly affect the resource conservation and commercial utilization of yams. In this study, typical yam resources including the species of D. opposita(wild and cultivated Ruichang yam from southern China, and Tiegun yam from northern China) and two landraces of D. alata(Longyan yam and Anyuan yam from southern China) were selected as materials. Nutritional traits and medicinal characteristics were determined and analyzed respectively. The results showed that there was no significant differences in the content of most nutrients between D. oppositaand D. alata,but most cultivated Ruichang yam of D. oppositashowed higher levels of starch, soluble sugar, sucrose, and ascorbate in tuber than that in yam from D. alata.Moreover, an UPLC-MS method was developed for identification and determination of medicinal characteristics in the two species. The results showed that allantoin can be detected in all selected samples. Cultivated Ruichang yam of D. oppositapossessed the highest allantoin content among the tested materials, and was significantly different with that in Tiegun yam and D. alata.Dioscin was not detected in D. alata.Overall, there was little difference in nutritional composition between D. oppositaand D. alata,but the medicinal quality of D. oppositawas better than that of D. alata.Due to the outstanding comprehensive quality, the local variety of cultivated Ruichang yam can be further developed and utilized.

Liquid-phase selective oxidation of o-chlorotoluene (OCT) to o-chlorobenzaldehyde (OCBD) with oxygen as the oxidant catalyzed by a cobalt acetate/manganese acetate/potassium bromide (Co(OAc)2/Mn(OAc)2/KBr) system was studied in a microchannel reactor using acetic acid doped with a small amount of water as the reaction medium. The reaction parameters were easily controlled by performing the reaction in a microchannel reactor. A selectivity as high as 71.8% for OCBD was achieved by maintaining the conversion of OCT at 10.3% under the optimal reaction conditions.

Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss of sensory or motor function. Restoration of the injured nerves requires a complex cellular and molecular response to rebuild the functional axons so that they can accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation with exogenous growth factors (GFs) is an emerging and versatile therapeutic strategy for promoting nerve regeneration and functional recovery. GFs activate the downstream targets of various signaling cascades through binding with their corresponding receptors to exert their multiple effects on neurorestoration and tissue regeneration. However, the simple administration of GFs is insufficient for reconstructing PNI due to their short half‑life and rapid deactivation in body fluids. To overcome these shortcomings, several nerve conduits derived from biological tissue or synthetic materials have been developed. Their good biocompatibility and biofunctionality made them a suitable vehicle for the delivery of multiple GFs to support peripheral nerve regeneration. After repairing nerve defects, the controlled release of GFs from the conduit structures is able to continuously improve axonal regeneration and functional outcome. Thus, therapies with growth factor (GF) delivery systems have received increasing attention in recent years. Here, we mainly review the therapeutic capacity of GFs and their incorporation into nerve guides for repairing PNI. In addition, the possible receptors and signaling mechanisms of the GF family exerting their biological effects are also emphasized.

A novel Lewis acid-catalyzed, highly efficient, practical, and atom-economical protocol for the synthesis of functionalized 1,2-dihydropyridine-3-carbonitrile derivatives in the presence of Bi(OTf)3(10 mol %) in tetrahydrofuran (2.0 mL) at 80 °C for 8 h in air is described, starting from readily accessed propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles. This cycloaddition protocol, which is scalable and proceeds under mild conditions, is amenable to the gram-scale construction of valuable 1,2-dihydropyridine-3-carbonitriles. Furthermore, the good functional group compatibility and broad scope of this strategy were demonstrated by a broad range of propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles, with yields ranging from 34 to 96%.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the oldest known and most dangerous diseases. Although the spread of TB was controlled in the early 20th century using antibiotics and vaccines, TB has again become a threat because of increased drug resistance. There is still a lack of effective treatment regimens for a person who is already infected with multidrug-resistant Mtb (MDR-Mtb) or extensively drug-resistant Mtb (XDRMtb). In the past decades, many research groups have explored the drug resistance profiles of Mtb based on sequence data by GWAS, which identified some mutations that were significantly linked with drug resistance, and attempted to explain the resistance mechanisms. However, they mainly focused on several significant mutations in drug targets (e.g. rpoB, katG). Some genes which are potentially associated with drug resistance may be overlooked by the GWAS analysis. Objective: In this article, our motivation is to detect potential drug resistance genes of Mtb using a heat diffusion model. Methods: All sequencing data, which contained 127 samples of Mtb, i.e. 34 ethambutol-, 65 isoniazid-, 53 rifampicin- and 45 streptomycin-resistant strains. The raw sequence data were preprocessed using Trimmomatic software and aligned to the Mtb H37Rv reference genome using Bowtie2. From the resulting alignments, SAMtools and VarScan were used to filter sequences and call SNPs. The GWAS was performed by the PLINK package to obtain the significant SNPs, which were mapped to genes. The P-values of genes calculated by GWAS were transferred into a heat vector. The heat vector and the Mtb protein-protein interactions (PPI) derived from the STRING database were inputted into the heat diffusion model to obtain significant subnetworks by HotNet2. Finally, the most significant (P < 0.05) subnetworks associated with different phenotypes were obtained. To verify the change of binding energy between the drug and target before and after mutation, the method of molecular dynamics simulation was performed using the AMBER software. Results: We identified significant subnetworks in rifampicin-resistant samples. Excitingly, we found rpoB and rpoC, which are drug targets of rifampicin. From the protein structure of rpoB, the mutation location was extremely close to the drug binding site, with a distance of only 3.97 Å. Molecular dynamics simulation revealed that the binding energy of rpoB and rifampicin decreased after D435V mutation. To a large extent, this mutation can influence the affinity of drug-target binding. In addition, topA and pyrG were reported to be linked with drug resistance, and might be new TB drug targets. Other genes that have not yet been reported are worth further study. Conclusion: Using a heat diffusion model in combination with GWAS results and protein-protein interactions, the significantly mutated subnetworks in rifampicin-resistant samples were found. The subnetwork not only contained the known targets of rifampicin (rpoB, rpoC), but also included topA and pyrG, which are potentially associated with drug resistance. Together, these results offer deeper insights into drug resistance of Mtb, and provides potential drug targets for finding new antituberculosis drugs.

Three (R,R)‐3,4‐diaminopyrrolidine‐based chiral N4ligands and corresponding iron complexes were synthesized. The complexes were applied to the asymmetric epoxidation of various α,β‐unsaturated ketones with H2O2as an oxidant and carboxylic acid as auxiliary. Good to excellent enantioselectivity (up to 97%) was achieved in the case of 2,2‐dimethylbutyric acid as an auxiliary. Asymmetric catalysis: Several chiral diaminopyrrolidine‐derived N4 ligands with and without a chiral sidearm have been designed and synthesized. We applied its chiral non‐heme iron complexes to the asymmetric epoxidation of α,β‐unsaturated ketones with H2O2in the presence of carboxylic acid. These complexes display remarkably high enantioselectivities (up to 97% ee) in the asymmetric epoxidation.

N-Unsubstituted cyclic imides were readily synthesized in deep eutectic solvent (DES) choline chloride (ChCl)/urea from anhydrides with urea. Urea serves as both a DES component and a nitrogen source, which endows the protocol with advantages of smooth reaction, easy separation of products, simple recovery and recycling of ChCl/urea.

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1and PRAMEtranscript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1and PRAMEwas associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1and PRAMEoverexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1and PRAMEtranscript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAMEtranscript analysis may improve the prognostication precision and better risk-stratify the patients.

This study focuses on developing an innovative multicriteria group decision-making (MCGDM) method to handle practical problems based on information description, information fusion and information measure. Given that various uncertain data exist in the process of managing problems, uncertain Z-numbers are introduced to represent evaluation information and measure information reliability simultaneously. Processing uncertain information requires the effective support of reliable tools; then, cloud models can be used to address uncertain Z-number information. First, uncertain Z-numbers are converted, and a novel concept of Z-trapezium-normal clouds (ZTNCs) is introduced. Next, the operations, power aggregation operators, and distance and likelihood measures of ZTNCs are defined. Subsequently, the likelihood power aggregation operator and the priority vector of the likelihood matrix are proposed. Moreover, a new MCGDM method is developed by combining the two kinds of proposed power aggregation operators with the likelihood measure. Finally, an illustrative example of new energy evaluation is provided to demonstrate the developed method, and its feasibility and validity are further verified by a comparative analysis with other existing methods. [ABSTRACT FROM AUTHOR]

Considering the R&D for upgrading the KL0and μdetectors in the Belle II experiment using a scintillator and silicon photomultiplier (SiPM), we designed a compact high-speed and low-noise preamplifier. The preamplifier demonstrated a good gain stability, bandwidth of 426MHz, baseline noise level of σ≈0.6mV, dynamic range of up to 170mVof the input signal amplitude, good time resolution of 20ps, and it can be comprehensively applied to SiPMs. Adopting pole-zero-cancelation in the preamplifier reduces both the rise and fall times of the SiPM signal, which can significantly improve the time resolution and reduce the pile-up when using a large SiPM or an array of SiPMs. Various combinations of the preamplifier and several types of SiPMs demonstrated time resolutions better than 50psfor most cases; when the number of detected photons was larger than 60, a time resolution of approximately 25pswas achieved.

A facile and effective alkoxylation protocol of quinoxalin-2(1H)-ones with primary or secondary alcohols via cross-dehydrogenative coupling under catalyst-free conditions has been disclosed. This method provides a powerful and convenient access to 3-alkoxylquinoxalin-2(1H)-ones in good to excellent yields by utilizing PhI(OTFA)2as an oxidant and allows to easily obtain potential drug molecules containing 3-alkoxylquinoxalin-2(1H)-one skeletons.

The thermal control system based on a combination of passive and active methods for a compact aerial camera used in the unmanned aerial vehicle system is studied. Integrated analysis and an experimental method are developed to ensure both low-power limit and high image quality of the camera. For rapid estimation of thermal behavior, we develop a thermal mathematic model based on a thermal network method that also offers an initial design reference for the active control system; then we develop a more complex integrated analysis method to analyze and optimize the thermal system, which allows us to get performance insights such as internal temperature gradient and airflow of the compact system. We also focus on analyzing the optical surface errors under thermal disturbance. Comparisons of interferometer test records and thermal-elastic simulation results are presented, and this comparison shows that the integrated optomechanical analysis method contributes to the success of optomechanical system design by ensuring thermal disturbance will not deform the optical surfaces beyond allowable limits. Finally, the design method is verified through a thermo-optic experiment.

The non-random three-dimensional (3D) organization of the genome in the nucleus is critical to gene regulation and genome function. Using high-throughput chromatin conformation capture, we generated chromatin interaction maps for Brassica rapaand Brassica oleraceaat a high resolution and characterized the conservation and divergence of chromatin organization in these two species. Large-scale chromatin structures, including A/B compartments and topologically associating domains, are notably conserved between B. rapaand B. oleracea, yet their KNOT structures are highly divergent. We found that genes retained in less fractionated subgenomes exhibited stronger interaction strengths, and diploidization-resistant duplicates retained in pairs or triplets are more likely to be colocalized in both B. rapaand B. oleracea. These observations suggest that spatial constraint in duplicated genes is correlated to their biased retention in the diploidization process. In addition, we found strong similarities in the epigenetic modification and Gene Ontology terms of colocalized paralogues, which were largely conserved across B. rapaand B. oleracea, indicating functional constraints on their 3D positioning in the nucleus. This study presents an investigation of the spatial organization of genomes in Brassicaand provides insights on the role of 3D organization in the genome evolution of this genus. The three-dimensional (3D) genomes of Brassica rapaand Brassica oleraceagenerated using Hi-C provide insights into the role of 3D organization in genome evolution. Specifically, stronger chromatin interaction is associated with gene retention during diploidization.

Well-dispersed Ni-CeOxnanoparticles grown on carbon nanotubes (CNTs) were successfully synthesized via a simple one-step co-reduction method. The structure and properties of the catalysts were investigated by XRD, XPS, SEM, TEM and ICP-OES. Among the prepared catalysts, Ni1-(CeO1.8)0.5/CNTs exhibited the highest catalytic activity, with 100% hydrogen selectivity and 80 molH2molNi−1h−1of hydrogen generation rate (HGR) for hydrogen generation from hydrazine under 1.0 M NaOH solution at 343 K. This superior catalytic performance might be attributed to the smaller sizes and amorphous states of Ni species in Ni1-(CeO1.8)0.5/CNTs, as well as the close attachment of Ni-CeOxNPs on CNTs.

The induction of neural regeneration is vital to the repair of spinal cord injury (SCI). While compared with peripheral nervous system (PNS), the regenerative capacity of the central nervous system (CNS) is extremely limited. This indicates that modulating the molecular pathways underlying PNS repair may lead to the discovery of potential treatment for CNS injury. Based on the gene expression profiles of dorsal root ganglion (DRG) after a sciatic nerve injury, we utilized network guided forest (NGF) to rank genes in terms of their capacity of distinguishing injured DRG from sham-operated controls. Gene importance scores deriving from NGF were used as initial heat in a heat diffusion model (HotNet2) to infer the subnetworks underlying neural regeneration in the DRG. After potential regulators of the subnetworks were found through Connectivity Map (cMap), candidate compounds were experimentally evaluated for their capacity to regenerate the damaged neurons. Gene ontology analysis of the subnetworks revealed ubiquinone biosynthetic process is crucial for neural regeneration. Moreover, almost half of the genes in these subnetworks are found to be related to neural regeneration via text mining. After screening compounds that are likely to modulate gene expressions of the subnetworks, three compounds were selected for the experiment. Of them, trichostatin A, a histone deacetylase inhibitor, was validated to enhance neurite outgrowth in vivovia an optic nerve crush mouse model. Our study identified subnetworks underlying neural regeneration, and validated a compound can promote neurite outgrowth by modulating these subnetworks. This work also suggests an alternative approach for drug repositioning that can be easily extended to other disease phenotypes.

The immobilization of ruthenium species on polyethylenimine (PEI) modified magnetic nanoparticles coated with silica afford a multifunctional catalyst (Fe3O4@SiO2@PEI@Ru(OH)x) for the aerobic oxidation/Knoevenagel condensation of alcohols and active methylene compounds. A wide scope of alcohols and malononitrile could be converted to their corresponding condensation products in excellent yields under mild conditions. This catalyst has advantages of leaching-free of ruthenium species and ease of recovery by an external magnet. The activity deactivation of the catalyst was investigated and was ascribed to the transformation of surface Ru3+to Ru4+in the process of aerobic oxidation of alcohols.

Global warming-associated increases in temperature, particularly at nighttime, are detrimental to rice yield and quality. Metabolomic profiling was used to examine and compare the short-term extreme high nighttime temperature-induced molecular perturbations in rice (Oryza sativa) coisogenic strains with contrasting heat-tolerances at the first stage of seed ripening. Compared to the heat-sensitive strain, antioxidant molecules were higher in abundance in the heat-tolerant strain, whereas the abundances of molecules involved in photosynthesis, nucleotide catabolism, and the S-adenosylmethionine (SAM) cycle varied only slightly. Thus, we proposed that the high abundance of antioxidant molecules in the heat-tolerant strain alleviated cellular oxidative stress, which protected photosynthesis, nucleotide catabolism, and the SAM cycle, leading to good grain filling.

A catalyst system consisting of copper (I) chloride, sodium 2-picolinate (PIC) and TEMPO has been found to be effective in the aerobic oxidative conversion of benzylic alcohols with aqueous ammonia to nitriles in the absence of organic solvent. Various benzyl alcohols were converted to their corresponding nitriles in high yields. The ligand PIC can be easily removed from the reaction mixture due to its water solubility, allowing for easy product purification.

This paper proposes two extended projection-based preference ranking organization methods for enrichment evaluations for multi-criteria decision making with hesitant fuzzy linguistic term sets (HFLTSs). We first utilize three linguistic scale functions to solve linguistic information transformation with differences in semantics. Correspondingly, we define projection and normalized projection measurements for HFLTSs. We then propose a projection-based difference measurement for HFLTSs while considering the risk appetite of decision-makers. The effectiveness and robustness of the proposals are demonstrated by their application to a practical example of green supply chain management problem, which is followed by sensitivity and comparative analyses. Finally, conclusions and future research directions are drawn.

ABSTRACTInduced Choquet integral is a powerful tool to deal with imprecise or uncertain nature. This study proposes a combination process of the induced Choquet integral and neutrosophic information. We first give the operational properties of simplified neutrosophic numbers (SNNs). Then, we develop some new information aggregation operators, including an induced simplified neutrosophic correlated averaging (I-SNCA) operator and an induced simplified neutrosophic correlated geometric (I-SNCG) operator. These operators not only consider the importance of elements or their ordered positions, but also take into account the interactions phenomena among decision criteria or their ordered positions under multiple decision-makers. Moreover, we present a detailed analysis of I-SNCA and I-SNCG operators, including the properties of idempotency, commutativity and monotonicity, and study the relationships among the proposed operators and existing simplified neutrosophic aggregation operators. In order to handle the multi-criteria group decision-making (MCGDM) situations where the weights of criteria and decision-makers usually correlative and the criterion values are considered as SNNs, an approach is established based on I-SNCA operator. Finally, a numerical example is presented to demonstrate the proposed approach and to verify its effectiveness and practicality.

The reductive amination of levulinic acid to N-substituted pyrrolidinones was performed in a continuous-flow microreactor (CFMR) in high yield, using formic acid as hydrogen source and acetonitrile as the reaction solvent. The developed protocol allows the avoidance of high boiling solvents such as DMSO and the additive triethylamine, more commonly associated with this synthetic transformation. As a result, the reaction products are more readily separated from the low boiling solvent. Graphical abstractThe continuous reductive amination of levulinic acid with amines to N-substituted pyrrolidones was performed in a continuous-flow microreactor in high yield, using formic acid as hydrogen source and acetonitrile as the reaction solvent under catalyst-free conditions.

It has been recently pointed out that the compositions of industrial alloys are originated from cluster-plus-glue-atom structure units in solid solutions. Specifically for Ni-based superalloys, after properly grouping the alloying elements into Al, Ni-like ($$ \overline{\text{Ni}} $$ Ni¯ ), γ′-forming Cr-like ($$ \overline{\text{Cr}}^{{\gamma^{\prime } }} $$ Cr¯γ′ ) and γ-forming Cr-like ($$ \overline{\text{Cr}}^{\gamma } $$ Cr¯γ ), the optimal formula for single-crystal superalloys is established [Al–$$ \overline{\text{Ni}} $$ Ni¯ 12](Al1$$ \overline{\text{Cr}}^{{\gamma^{\prime } }}_{0.5} \overline{\text{Cr}}^{\gamma }_{1.5} $$ Cr¯0.5γ′Cr¯1.5γ ). The Co substitutions for Ni at the shell sites are conducted on the basis of the first-generation single-crystal superalloy AM3, formulated as [Al–Ni12−xCox](Al1Ti0.25Ta0.25Cr1W0.25Mo0.25), with x= 1.5, 1.75, 2 and 2.5 (the corresponding weight percents of Co are 9.43, 11.0, 12.57 and 15.71, respectively). The 900 °C long-term aging follows the Lifshitz–Slyozov–Wagner theory (LSW theory), and the Co content does not have noticeable influence on the coarsening rate of γ′. The microstructure and creep behavior of the four (001) single-crystal alloys are investigated. The creep rupture lifetime is reduced as Co increases. The alloy with the lowest Co (9.43 Co) shows the longest lifetime of about 350 h at 1050 °C/120 MPa, and all the samples show N-type rafting after creep tests.

Objective: To explore the effects of different dosages of 4-nonylphenol (4-NP) on the fatty acid synthesis and estrogen receptor α (ERα) expression in the livers of F1 and F2 rats. Method: Pregnant rats were randomly divided into four groups: control, NP-5 (5 μg per kg per day), NP-25 (25 μg per kg per day) and NP-125 (125 μg per kg per day). 4-NP was gavaged from gestation day (GD) 6 to postnatal day (PND) 21. Some female rats from the experimental groups were mated with male rats from the control group to obtain the F2 rats. F1 generation rats (23 weeks old) and F2 generation rats (13 weeks old) were killed to detect blood biochemistry and the expression of genes and proteins. Results: Compared with the control group, 4-NP (NP-5, NP-25 and NP-125) can increase the liver organ coefficient of the F1 male offspring (P< 0.05 or P< 0.01). The concentration of high density lipoprotein (HDL) in the F1 female NP-5 group was significantly higher than that of the control group (P< 0.01); other indicators had not changed, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and low density lipoprotein (LDL). As the dosage of 4-NP increased, more significant changes of blood biochemistry were found, especially in the NP-125 rats (P< 0.05 or P< 0.01). The changes of histopathology by liver biopsy were consistent with biochemical indices of blood (P< 0.05 or P< 0.01). Compared with the control group, the expression of genes involved in fatty acid synthesis increased significantly (P< 0.05 or P< 0.01), and the degrees of increase were proportional to the dose of 4-NP, as measured by lipoprotein lipase (Lpl), fatty acid synthetase (Fas), sterol regulatory element-binding protein 1 (Srebp-1) and peroxisome proliferator-activated receptor (Ppar)-γ. The expression of genes and proteins of ERα were changed significantly, as well (P< 0.05 or P< 0.01). The above changes in the liver tissues of F2 generation rats were consistent with the F1 generation rats. Conclusion: Perinatal exposure to 4-NP can affect the synthesis of fatty acid in the livers of F1 and F2 generation rats. The low expression of ERα may be one of the mechanisms by which 4-NP affected fatty acid synthesis in the livers of rats.

The precipitation of the lamellar-shaped M23C6carbide within the dendritic matrix of a cobalt-base superalloy during thermal exposure at 1000 °C has been investigated. Such a precipitation is not commonly observed in cobalt-base superalloys. It is found that M23C6particles nucleate preferentially at stacking faults (SFs) in the dendritic matrix and grow along the SFs to develop a lamellar character. Additionally, a Cr depletion zone is observed in the vicinity of the lamellar M23C6carbide, which strongly supports the presence of Suzuki segregation.

In this study, comprehensive multi-criteria decision-making (MCDM) methods are investigated under bipolar neutrosophic environment. First, the operations of BNNs are redefined based on the Frank operations considering the extant operations of bipolar neutrosophic numbers (BNNs) lack flexibility and robustness. Subsequently, the Frank bipolar neutrosophic Choquet weighted Bonferroni mean operator and the Frank bipolar neutrosophic Choquet geometric Bonferroni mean operator are proposed based on the Frank operations of BNNs. The proposed operators simultaneously consider the interactions and interrelationships among the criteria by combining the Choquet integral operator and Bonferroni mean operators. Furthermore, MCDM methods are developed based on the proposed aggregation operators. A numerical example of plant location selection is conducted to explain the application of the proposed methods, and the influences of parameters are also discussed. Finally, the proposed methods are compared with several extant methods to verify their feasibility.

The intrinsic relationship between the microstructure evolution and thermal fatigue behavior of a single-crystal cobalt-base superalloy has been investigated. The thermal fatigue tests are performed cyclically between room temperature and 1050 °C using V-notch plate specimens. Three states of thermal fatigue specimens are selected: the as-cast, solutionized as well as aged states. The solution treatment is carried out at 1260 °C for 24 h, which results in the dissolution of most of interdendritic continuous primary carbides. The subsequent aging treatment is carried out at 1100 °C for 100 h after solution treatment, resulting in the precipitation of a profusion of chain- and point-like M23C6carbides in the matrix. The results indicate that the heat treatment can improve the thermal fatigue properties of the alloy and the effect of the solution treatment is more prominent than that of the aging treatment. The coarse and continuously distributed primary carbides in the as-cast state are changed into small and discontinuous distribution by heat treatment, which is the dominant factor in the improvement of thermal fatigue property. Additionally, the effect of oxidation behavior during thermal fatigue test on the thermal fatigue behavior is also studied.

To observe the clinical efficacy of electroacupuncture (EA) on Alzheimer’s disease (AD). A total of 50 AD patients were randomly allocated into a Western medication (WM) group (n=25) and an acupuncture plus medication (APM) group (n=25). Patients in the WM group took oral huperzine A capsules. In addition to huperzine A capsules, patients in the APM group also received EA at Shenting (GV 24), Baihui (GV 20), Dazhui (GV 14), Fengfu (GV 16), Mingmen (GV 4) and Yongquan (KI 1). The needles on the above points were connected to G6805-II electric stimulator [3 pairs: Shenting (GV 24) and Baihui (GV 20); Dazhui (GV 14) and Fengfu (GV 16); and bilateral Yongquan (KI 1)]. The needles were retained 25 min. The treatment was done once a day, and 10 times made up a course of treatment. The patients received a total of 3 treatment courses. There was a 3-day interval between two courses. The mini-mental state examination (MMSE) and Hasegawa dementia scale revised (HDS-R) were conducted before and after treatment. The clinical efficacies were evaluated when the treatment was completed. Before treatment, there were no between-group statistical differences in MMSE and HDS-R scores (both P>0.05). After treatment, the MMSE and HDS-R scores in the APM group were significantly higher than those in the WM group (both P<0.05). The total effective rate in the APM group was 88.0%, versus 76.0% in the WM group, showing a statistical difference (P<0.05). EA is effective for AD and can improve clinical symptoms in AD patients. 观察电针治疗阿尔茨海默病(AD)的临床疗效, 探讨其临床应用价值。 将50例AD 患者采用随 机数字表分为2组, 每组25例。西药组口服石杉碱甲胶囊; 针药组在口服石杉碱甲胶囊基础上加用电针治疗, 穴位 选神庭、百会、大椎、风府、命门和涌泉, 针刺得气后接G6805-II型电针治疗仪(神庭与百会为一组, 大椎和风 府为一组, 双侧涌泉为一组)。刺激量以患者能够耐受为度。每次留针25 min, 每日1次, 连续10次为1疗程, 两个 疗程间休息3 d, 共治疗3个疗程。治疗前后进行简易精神状态检查量表(MMSE)和修订后的长谷川智能量表(HDS-R) 评分, 并于治疗结束后进行临床疗效评价。 治疗前两组MMSE 及HDS-R 评分均无统计学差异(均P>0.05)。 治疗后针药组MMSE 和HDS-R 评分均明显高于西药组(均P<0.05)。治疗后针药组总有效率为88.0%, 西药组为 76.0%, 针药组的临床疗效优于西药组(P<00.05)。 电针是治疗AD 的有效方法, 能有效改善AD 患者的临床 症状, 提高疗效。

Patients with chronic hepatitis B virus (HBV) infection are at high risk for progressing to decompensated cirrhosis and hepatocellular carcinoma (HCC). Although long-term treatment with nucleos(t)ide analogues (NAs) benefits patients with chronic hepatitis B (CHB), many develop HCC. Therefore, the clinical outcomes of patients CHB who undergo long-term treatment with NAs remain to be identified. The aim of this study therefore was to evaluate the risk and predictors of patients with CHB who develop hepatitis B-induced HCC.

Nitriles were synthesized from the aerobic oxidation of amines over commercially available catalysts, which were activated carbon-supported ruthenium catalysts (Ru/AC). The 5%Ru/AC catalyst can tolerate a wide range of substrates, such as aromatic, aliphatic, and heterocyclic amines, and afford the target nitriles in good-to-excellent yields. The 5%Ru/AC catalyst was easily recovered and no ruthenium leaking took place in the catalytic run.Nitriles were synthesized from the aerobic oxidation of amines over commercially available catalysts, which were ruthenium supported on activated carbon catalysts (Ru/AC). This protocol is simple, environment friendly, and the 5%Ru/AC catalyst can tolerate a wide range of substrates, such as aromatic, aliphatic, and heterocyclic amines, and afford the target nitriles in good to excellent yields.

Mycobacterium tuberculosis(Mtb), the pathogen of tuberculosis (TB), is one of the most infectious bacteria in the world. The traditional strategy to combat TB involves targeting the pathogen directly; however, the rapid evolution of drug resistance lessens the efficiency of this anti-TB method. Therefore, in recent years, some researchers have turned to an alternative anti-TB strategy, which hinders Mtb infection through targeting host genes. In this work, using a theoretical genetic analysis, we identified 170 Mtb infection-associated genes from human genetic variations related to Mtb infection. Then, the agents targeting these genes were identified to have high potential as anti-TB drugs. In particular, the agents that can target multiple Mtb infection-associated genes are more druggable than the single-target counterparts. These potential anti-TB agents were further screened by gene expression data derived from connectivity map. As a result, some agents were revealed to have high interest for experimental evaluation. This study not only has important implications for anti-TB drug discovery, but also provides inspirations for streamlining the pipeline of modern drug discovery.

An elegant Lewis acid catalyzed, protection-free, and straightforward synthetic strategy for the assembly of a series of sophisticated polycyclic quinoline skeletons employing propargylic alcohols and 2-vinylanilines as the substrates in the presence of Yb(OTf)3(10 mol %) and AgOTf (10 mol %) in tetrahydrofuran has been described. This annulation protocol, which proceeds through a sequential Meyer–Schuster rearrangement/nucleophilic substitution/deprotonation sequence, provides a versatile, practical, and atom-economical approach for accessing quinoline derivatives in moderate-to-good yields.

The effect of Hf on the grain refinement of as-cast aluminum was investigated using optical microscopy, electron microscopy and X-ray diffraction. The result shows that the grain size of studied alloy decreases effectively with the addition of Hf, Hf can react with Al to form Al3Hf particles during the solidification, the primary Al3Hf particles are highly potent nucleants for Al and the nanoscale coherent Al3Hf particles can inhibit the grain growth by pinning effect. The grain refinement mechanism of studied alloys was verified by the solute theory and the crystallography study, and it can be divided into two distinct types: At low Hf contents, there are no primary Al3Hf phases to form, the acquired grain refinement is primarily attributed to the constitutional undercooling induced by the Hf solute. At medium and high Hf contents, both Hf solute and Al3Hf particles contribute to the refinement.

Organic molecules that with mechanoluminescence properties exhibits fluorescence variation under hydrostatic pressure.

Type-2 fuzzy sets/numbers (T2FSs/T2FNs) attract more and more attention in fuzzy decision field. The existing studies mostly focus on the general properties of T2FS, or interval type-2 fuzzy number whose membership degrees are denoted by intervals. A new form of T2FN named triangular type-2 fuzzy number is proposed, whose primary and secondary memberships both have the continuous triangular feature. For aggregating the triangular type-2 fuzzy information, two operators are also defined. Based on them, a method is developed to handle the duplex linguistic group multi-criteria decision making problems and rank the alternatives. Finally, an example is provided to show the feasibility of the method.

AbstractThis paper presents a fuzzy multi-criteria decision-making (FMCDM) approach based on cloud model and prospect theory. In addition, a reference point selection method is developed according to the evaluations of the potential customer or similar consumers regarding certain items. An example of purchasing decision problems is provided in order to illustrate the applicability of the proposed approach. A comparative analysis of the proposed approach is also performed in order to verify its feasibility.