T790M mutation upconversion fluorescence biosensor via mild ATRP strategy and site-specific DNA cleavage of restriction endonuclease.

A unique combination of a specific nucleic acid restriction endonuclease (REase) and atom transfer radical polymerization (ATRP) signal amplification strategy was employed for the detection of T790M mutations prevalent in the adjuvant diagnosis of lung cancer. REase selectively recognizes and cleaves T790M mutation sites on double-stranded DNA formed by hybridization of a capture sequence and a target sequence. At the same time, the ATRP strategy resulted in the massive aggregation of upconverted nanoparticles (UCNPs), which significantly improved the sensitivity of the biosensor. In addition, the UCNPs have excellent optical properties and can eliminate the interference of autofluorescence in the samples, thus further improving the detection sensitivity. The proposed upconversion fluorescent biosensor is characterized by high specificity, high sensitivity, mild reaction conditions, fast response time, and a detection limit as low as 0.14 fM. The performance of the proposed biosensor is comparable to that of clinical PCR methods when applied to clinical samples. This work presents a new perspective for assisted diagnosis in the pre-intervention stage of tumor diagnostics in the early stage of precision oncology treatments.

Artificial neural network-based shelf life prediction approach in the food storage process: A review.

The prediction of food shelf life has become a vital tool for distributors and consumers, enabling them to determine storage and optimal edible time, thus avoiding unexpected food waste. Artificial neural network (ANN) have emerged as an effective, fast and accurate method for modeling, simulating and predicting shelf life in food. ANNs are capable of tackling nonlinear, complex and ill-defined problems between the variables without prior knowledge. ANN model exhibited excellent fit performance evidenced by low root mean squared error and high correlation coefficient. The low relative error between actual values and predicted values from the ANN model demonstrates its high accuracy. This paper describes the modeling of ANN in food quality prediction, encompassing commonly used ANN architectures, ANN simulation techniques, and criteria for evaluating ANN model performance. The review focuses on the application of ANN for modeling nonlinear food quality during storage, including dairy, meat, aquatic, fruits, and vegetables products. The future prospects of ANN development mainly focus on optimal models and learning algorithm selection, multiple model fusion, self-learning and self-correcting shelf-life prediction model development, and the potential utilization of deep learning techniques.

ANN-based food shelf life prediction methods are reviewed.This paper discusses application of ANN in the food storage process.BPNN is the mainstream ANN architecture used for the prediction of food quality.ANNs are useful for prediction of outputs with high accuracy.Future trends of ANN in the agri-supply chain are evaluated.

Divergent Synthesis of 1,1-Carbonyl Amino Alkyl Borons from Indoles.

α-Boryl carbonyl species and α-boryl amino compounds are valuable and important frameworks in organic synthesis. However, the strategies that could merge the two scaffolds into one compound, named 1,1-carbonyl amino alkyl boron, are elusive and underdeveloped. Herein, we present an efficient method that could address this gap and produce 1,1-carbonyl amino alkyl borons from readily accessible indoles via oxidation by m-CPBA or oxone. This reaction features operational simplicity, divergent synthesis, broad substrate scope, and valuable products.

Background-free and signal-amplified upconversion fluorescent biosensing platform for sensitive detection of CYFRA21-1.

Accurate and ultrasensitive detection of cytokeratin 19 fragment (CYFRA21-1) is of vital importance for screening and diagnosis of potential lung cancer patient. In this paper, surface-modified upconversion nanomaterials (UCNPs) capable of aggregation by atom transfer radical polymerization (ATRP) were used as luminescent materials for the first time to achieve signal-stable, low-biological background, and sensitive detection of CYFRA21-1. Upconversion nanomaterials (UCNPs) feature extremely low biological background signals and narrow emission peaks, making them ideal sensor luminescent materials. The combination of UCNPs and ATRP not only improves sensitivity, but also reduces biological background interference for detecting CYFRA21-1. The target CYFRA21-1 was captured by specific binding of the antigen and the antibody. Subsequently, the end of the sandwich structure with the initiator reacts with monomers modified on UCNPs. Then, massive UCNPs are aggregated by ATRP that amplify the detection signal exponentially. Under optimal conditions, a linear calibration plot of the logarithm of CYFRA21-1 concentration versus the upconversion fluorescence intensity was obtained in the range of 1 pg/mL to 100 µg/mL with a detection limit of 38.7 fg/mL. The proposed upconversion fluorescent platform can distinguish the analogues of the target with excellent selectivity. Besides, the precision and accuracy of the developed upconversion fluorescent platform were verified by clinical methods. As an enhanced upconversion fluorescent platform of CYFRA21-1, it is expected to be useful in screening potential patients with NSCLC and provides a promising solution for the high-performance detection of other tumor markers.

Arylation of Terminal Alkynes: Transition-Metal-Free Sonogashira-Type Coupling for the Construction of C(sp)-C(sp2) Bonds.

Alkynes are attractive synthons for organic chemistry. Despite the prevalence of transition-metal-catalyzed Sonogashira reactions, a transition-metal-free version of the arylation of terminal alkynes is elusive. Herein, we report an efficient transition-metal-free Sonogashira-type coupling reaction for the one-pot arylation of alkynes to construct C(sp)-C(sp2) bonds from a tetracoordinate boron intermediate with NIS as a mediator. With its high efficiency, wide substrate range, and good functional group tolerance, this method is further supported by the gram-scale synthesis and subsequent modification of complex molecules.

Quantitative evaluation of therapy options for relapsed/refractory diffuse large B-cell lymphoma: A model-based meta-analysis.

New therapies for relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL) have emerged in recent years, but there have been no comprehensive quantitative comparisons of the efficacy of these therapies. In this study, the efficacy characteristics of 11 types of treatment strategy and 63 treatment regimens were compared by model based meta-analysis. We found that compared with monotherapy, association therapy had significant benefits in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). However, whereas treatment regimens involving chemotherapy contributed to significant improvements in ORR and PFS, OS was not improved. In terms of treatment strategy, we identified chemotherapy in association with immunotherapy sequential autologous stem cell transplantation (ASCT), the association of two different types of immunotherapies, chemotherapy sequential ASCT, chemotherapy in association with immunotherapy, and chemotherapy in association with two types of immunotherapies as showing better efficacy. With respect to specific treatment regimens, we found that the following had better efficacy: rituximab in association with inotuzumab ozogamicin; rituximab in association with carmustine, etoposide, cytarabine, and melphalan sequential ASCT (R-BEAM+ASCT); lenalidomide in association with rituximab, etoposide, cisplatin, cytarabine, and methylprednisolone; iodine-131 tositumomab in association with BEAM sequential ASCT; and chemotherapy sequential chimeric antigen receptor T-cell immunotherapy, with median OS of 48.2, 34.2, 27.8, 25.8, and 25 months, respectively. Moreover, with respect to association therapy, there was a strong correlation between the 6-month PFS and 2-year OS. The findings of this study provide the necessary quantitative information for clinical practice and clinical trial design for the treatment of r/rDLBCL.

A highly sensitive, eco-friendly electrochemical assay for alkaline phosphatase activity based on a photoATRP signal amplification strategy.

Alkaline phosphatase (ALP) is a significant hydrolase enzyme found in living organisms, and the dysregulation of its physiological activity has been correlated with a variety of diseases. Exploring the activity of ALP has important implications for biomedical research and clinical diagnosis. Accordingly, we have developed a novel, highly sensitive electrochemical biosensor for the analysis of ALP. Based on photoinduced atom transfer radical polymerisation (photoATRP), this strategy combined a fabricated biosensor with hydrolysate produced by the hydrolysis of O-phosphoethanolamine by ALP. Furthermore, for signal amplification, photoATRP synthesises uses polymers with plentiful binding sites for ferrocenylmethyl methacrylate, and by using a photoredox catalyst under blue light irradiation to perform this without the need for copper complexes, it is beneficial for environmental protection compared to traditional atom transfer radical polymerisation (ATRP). The biosensor had a linear range of 10-150 mU·mL-1, with R2 = 0.998, and detection limits as low as 2.12 mU·mL-1. Moreover, by exhibiting outstanding selectivity and interference resistance in human serum samples, this sensor has great potential for practical applications.

Construction of boron-stereogenic compounds via enantioselective Cu-catalyzed desymmetric B-H bond insertion reaction.

Compared with the well-developed carbon-stereogenic chemistry, the construction of boron-stereogenic compounds remains undeveloped and challenging. Herein, the previously elusive catalytic enantioselective construction of boron-stereogenic compounds has been achieved through enantioselective desymmetric B-H bond insertion reaction. The B-H bond insertion reaction of 2-arylpyridine-boranes with versatile diazo compounds under chiral copper catalyst can afford boron-stereogenic compounds with good to excellent enantioselectivity. Moreover, the synthetic utility of this reaction is demonstrated by the scalability and downstream transformations. DFT calculations provide insights into the reaction mechanism and the origin of stereoselectivity.

An electrochemical biosensor based on ARGET ATRP with DSN-assisted target recycling for sensitive detection of tobacco mosaic virus RNA.

Herein, an electrochemical biosensor for detecting tobacco mosaic virus (TMV) RNA is constructed by activator regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) combined with duplex-specific nuclease (DSN)-assisted target recycling. First, the captured DNA (cDNA) is self-assembled on the electrode surface and hybridizes with the TMV RNA (tRNA) to form cDNA/tRNA hybrids. And then the initiator of ARGET ATRP (α-bromoisobutyric acid, BMP) is attached to the cDNA via an amide bond and later triggers ARGET ATRP. Many electroactive monomers (ferrocenylmethyl methacrylate, FMMA) are polymerized and a remarkable electrical signal response of ferrocene (Fc) is obtained. However, with the present of DSN, DSN cleaves the cDNA/tRNA hybrid and releases tRNA to hybridize with another cDNA, thereby causing significant shortening of the length of the cDNA. The number of polymer chains on the electrode surface is drastically reduced, which is followed by a noticeable reduction in the signal of Fc. The method shows high sensitivity, superior selectivity, excellent stability and good reproducibility under optimal conditions with the limit of detection (LOD) of 2.9 fM. Furthermore, the biosensor showed satisfactory applicability in detecting tRNA in real samples, thereby demonstrating the potential of the method for practical TMV RNA detection.

Nanopore/Illumina Hybrid Genome Sequence Resource for Corynespora cassiicola Strain XJ Infecting Rubber Tree in China.

Corynespora cassiicola is a ubiquitous pathogenic fungus that can infect a broad range of plant hosts. Corynespora leaf fall, caused by C. cassiicola, is one of the major diseases on rubber tree in China. This disease is having an increasing affect on natural rubber production worldwide. In this study, by combining the Nanopore and Illumina sequencing technologies, we present the chromosome-scale genome sequence of the rubber tree-sampled C. cassiicola strain XJ collected in the subtropical region of China. The assembly consists of 23 scaffolds (N50 = 4.62 Mb) with an estimated genome size of 44.42 Mb (only 166 non-ATCG bases) and 16,108 protein-coding genes. The genome will provide a valuable resource for further research on the pathogenesis and comparative genomics of C. cassiicola on rubber tree and other hosts.

Quantitative study on the efficacy of acupuncture in the treatment of menopausal hot flashes and its comparison with nonhormonal drugs.

OBJECTIVE: This study aimed to compare the efficacy of acupuncture to that of sham acupuncture, placebo pills, and nonhormonal drugs to provide the necessary quantitative information for establishing medication guidelines for menopausal hot flashes. METHODS: A comprehensive literature search was performed using public databases. Randomized clinical studies on acupuncture therapy for the treatment of hot flashes in menopausal women were identified. A time-course model was established to describe the efficacy characteristics of acupuncture and sham acupuncture, which were compared with the efficacy of nonhormonal drugs and placebo pills reported in the literature. RESULTS: A total of 17 studies involving 1,123 participants were included. The quality of all the studies included in the analysis is medium to high, and there was no obvious risk of bias. It was found that the baseline number of hot flashes was an important factor affecting the efficacy of acupuncture and sham acupuncture. After correcting the baseline to eight hot flashes per day, the frequency of hot flashes decreased from baseline for traditional acupuncture (TA), electro-acupuncture (EA), TA&EA (merger analysis of TA and electro-acupuncture), and sham acupuncture were 3.1 (95% confidence interval [CI]: 2.8-3.4), 3.6 (95% CI: 3.2-4.0), 3.2 (95% CI: 2.9-3.5), and 2.6 (95% CI: 2.2-3.0) times/d at week 8, respectively. Compared with findings reported in the literature, we found the efficacy of electro-acupuncture was comparable to that of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and neuroleptic agents such as gabapentin and escitalopram. Furthermore, the efficacy of TA&EA (merged) was significantly higher than that of placebo pills (2.3, 95% CI: 1.8-2.9). CONCLUSIONS: The efficacy of TA&EA (merged) was higher than that of sham acupuncture and significantly higher than that of placebo pills. The efficacy of electro-acupuncture was higher than that of traditional acupuncture, significantly higher than that of sham acupuncture, and comparable to that of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and neuroleptic agents.

Efficacy of triptans for the treatment of acute migraines: a quantitative comparison based on the dose-effect and time-course characteristics.

OBJECTIVES: This study aimed to establish a pharmacodynamic model to quantitatively compare the efficacy characteristics of seven kinds of triptans and their different dosage forms in the treatment of acute migraines. METHODS: Clinical studies of triptans in the treatment of acute migraines were comprehensively searched in the public databases. Pharmacodynamic models were established to describe the dose-effect and time-course of each kind of triptan for the proportion of patients who became pain free or had pain relief. RESULTS: A total of 92 articles involving 47,376 subjects were included in the analysis. After eliminating the placebo effect, oral eletriptan (40 mg) had the highest efficacy among all oral drugs at the maximum approved dose, and the proportion of patients who became pain free and had pain relief were 30.9% and 37.9% at 2 h, respectively. However, oral naratriptan (2.5 mg) had the lowest efficacy, and the proportion of patients who became pain free and had pain relief was 10.3% and 21.6% at 2 h, respectively. The efficacy of subcutaneous administration was significantly higher than that of oral administration, and the efficacy of nasal spray administration was comparable to that of oral administration. Regarding the dose-effect, the efficacy of the sumatriptan nasal spray significantly increased within the FDA (Food and Drug Administration)-approved dose range. When the dose was increased from 5 to 20 mg of sumatriptan nasal spray, the proportion of patients who became pain free and had pain relief increased by 16.8% and 18.3% at 2 h, respectively. Regarding the time-course, the time of onset of subcutaneous sumatriptan (6 mg) was the fastest, and the fraction of patients who were pain free at 2 h accounted for 90.6% of that at 4 h. CONCLUSIONS: This study evaluated the efficacy characteristics of seven kinds of triptans and their different dosage forms. The present findings provide necessary quantitative information for migraine medication guidelines.