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Abstract Objective We aim to develop a predictive model for lymphovascular invasion (LVI) in patients with invasive breast cancer (IBC), using magnetic resonance imaging (MRI)-based radiomics features. Methods A total of 204 patients with IBC admitted to our hospital were included in this retrospective study. The data was split into training and validation sets at a 7:3 ratio. Feature normalization was conducted, followed by feature selection using ANOVA, correlation analysis, and LASSO in the training set. The final step involved building a logistic regression model. The LVI prediction models were established by single sequence image and combined different sequence images as follows: A: prediction model based on the optimal sequence in the 7-phase enhanced MRI scans; B: prediction model based on the optimal sequences in the sequences T1WI, T2WI, and DWI; and C: the combined model based on the optimal sequences selected from A and B. Subjects' work characteristic curves (ROC) and decision curves (DCA) were plotted to determine the extent to which they predicted LVI performance in the training and validation sets. Simultaneously, nomogram models were constructed by integrating radiomics features and independent risk factors. In addition, an additional 16 patients from the center between January and August 2024 were collected as the Nomogram external validation set. The ROC and DCA were used to evaluate the performance of the model. Results In the enhanced images, Model A built based on the enhanced 2-phase achieved the best average AUC, with a validation set of 0.764. Model B built based on the T2WI had better results, with a validation set of 0.693. Model C built by combining enhanced 2-phase and T2WI sequences had a mean AUC of 0.705 in the validation set. In addition, the tumor size, whether the tumor boundary was clear or not, and whether there was a coelom in the tumor tissue had a statistically significant effect on the LVI of IBC, and a clinical-radiomics nomogram was established. DCAs as well as Nomogram also indicate that Model A has good clinical utility. The AUC of the nomogram in the training set, internal validation set, and external validation set were 0.703, 0.615, and 0.609, respectively. The DCA also showed that the radiomics nomogram combined with clinical factors had good predictive ability for LVI. Conclusion In IBC, MRI radiomics can serve as a noninvasive predictor of LVI. The clinical-MRI radiomics model, as an efficient visual prognostic tool, shows promise in forecasting LVI. This highlights the significant potential of pre-radiomics prediction in enhancing treatment strategies.

Salmonella is an important cause of foodborne diseases worldwide, with a high detection rate in fresh meat. Rapid, accurate and sensitive detection of Salmonella is crucial in safeguarding food safety and people’s health. Electrochemical aptamer-based sensors, integrating the advantages of both aptamers and electrochemical sensors in terms of recognition specificity and sensitivity, attract much attention, thus having the potential for application in qualitative and quantitative detection of Salmonella. However, most existing reviews focus on the preparation process of sensors, while little information is available regarding the correlation between the structure and properties of Salmonella, leading to the lack of a direct theoretical basis for the design and improvement of sensors. Therefore, based on the structure and properties of Salmonella, this article establishes its internal connection with aptamer-based sensors, and summarizes the electrode modification materials, aptamer fixation on the working electrode, the signal sensing strategies and the signal amplification strategies, in order to provide a reference for the rapid detection of Salmonella and other foodborne pathogenic bacteria.

Abstract Background Healthy eating is one of the most important nonpharmacologic treatments for patients with atherosclerosis(AS). However, it is unclear how elderly AS patients in western China perceive their dietary status and which type of nutritional assistance they would be willing to receive. Therefore, the primary purpose of this study was to understand the level of knowledge about current dietary habits and healthy eating habits among elderly AS patients in western China, and the secondary purpose was to identify acceptable nutritional assistance measures or pathways for those patients to help them manage disease progression. Methods An implementation study approach was used to recruit elderly patients with AS-related diseases in western China for semistructured interviews. Results 14 participants were included in the study, and the following three themes were identified from the interviews:(1) the diet with regional characteristics; (2) low nutrition-related health literacy; (3) complex attitudes towards nutritional assistance. Most participants had misconceptions about healthy eating, and the sources of their knowledge might not be trustworthy. Participants expressed a preference for personalized nutritional assistance, especially that provided by medical-nursing combined institutions. Conclusion Patients in western China need nutritional assistance for their regional dietary habits; therefore, healthy dietary patterns consistent with the regional culture are proposed to improve the prevailing lack of knowledge about healthy diets, improve the dietary structure of patients, and control the development of the disease.

Background: Association of asthma with the risk of cardiovascular disease has not been fully elucidated. So, this study tried to explore the genetic effect of asthma on five cardiovascular diseases and 90 peripheral cardiovascular proteins to answer the above topic. Methods: Instrumental variables predicting asthma was extracted from its genome-wide association study data. Two-sample and multivariate MR approaches were used to assess the genetic association of exposure factor (i.e., asthma) with outcome factors (i.e., hypertension, atrial fibrillation, angina pectoris, myocardial infarction, heart failure, and 90 peripheral cardiovascular proteins). Results: First, asthma nominally increased the risk of hypertension and atrial fibrillation (OR = 1.009, 95%CI = 1.003–1.016, P = 0.004; OR = 1.074, 95%CI = 1.024–1.127, P = 0.003). Second, of the 90 cardiovascular proteins, asthma was associated with the increased levels of tumor necrosis factor ligand superfamily member 14 and CC motif chemokine 4 (β = 0.145, 95%CI = 0.077–0.212, P = 2.936e-05; β = 0.128, 95%CI = 0.063–0.193, P = 1.036e-04). Third, CC motif chemokine 4 increased the risk of hypertension (P = 0.043); and after adjusting for this protein, asthma still increased the risk of hypertension, but the strength of its P-value changed from 0.004 to 0.011. Conclusion: Asthma was a risk factor for hypertension and atrial fibrillation at the genetic level, and CC motif chemokine 4 might play a mediating role in the mechanism by which asthma promoted hypertension. Thus, effective control of asthma may help reduce the risk of some cardiovascular diseases in older adults.

Abstract Background Neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) are closely related to the prognosis of patients with non‐small cell lung cancer, but their effect on extensive‐stage small cell lung cancer (ES‐SCLC) remains uncertain. Methods This retrospective study was conducted in ES‐SCLC patients treated with first‐line atezolizumab or durvalumab and platinum‐etoposide. Clinical data from three hospitals were analyzed. Significant risk factors for survival were identified using descriptive statistics and Cox regression. Homogeneity was assessed using t‐tests or nonparametric tests. Kaplan‐Meier analysis revealed an association between high NLR level and median PFS and OS. Results A total of 300 ES‐SCLC patients were included in the study. Cox regression analysis revealed that an elevated NLR level after the second treatment cycle (defined as NLRT2) was an independent prognostic factor for survival. Stratifying patients based on median NLRT2 showed significant differences in both PFS (HR: 1.863, 95% CI: 1.62–2.12, p

BackgroundType 2 diabetes mellitus(T2DM) is characterized by hyperglycemia. Gut microbiome adjustment plays a positive part in glucose regulation, which has become a hotspot. Probiotics have been studied for their potential to control the gut flora and to treat T2DM. However, the conclusion of its glucose-lowering effect is inconsistent based on different probiotic intervention times.ObjectivesTo comprehensively evaluate how various probiotic intervention times affect glycemic control in people with T2DM.MethodsWe retrieved PubMed, Embase, Web of Science, and Cochrane Library on randomized controlled trials(RCTs)regarding the impact of probiotics on glycemic control in patients with T2DM from the inception to November 16, 2023. Separately, two researchers conducted a literature analysis, data extraction, and bias risk assessment of the involved studies. We followed the PRISMA guidelines, used RevMan 5.4 software for meta-analysis, and assessed the risk of bias by applying the Cochrane Handbook for Systematic Reviews 5.1.0.ResultsWe included eight RCTs with 507 patients. Meta-analysis revealed that the use of probiotics might considerably reduce levels of glycosylated hemoglobin (HbA1c) {mean deviation (MD) = -0.33, 95% confidence interval (CI) (-0.59, -0.07), p = 0.01}, Insulin {standard mean deviation (SMD) = -0.48, 95% CI (-0.74, -0.22), p = 0.0003} and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR){SMD = -1.36, 95% CI (-2.30, -0.41), p = 0.005} than placebo group. No statistically significant differences were found regarding fasting blood glucose (FBG) and body mass index (BMI) {SMD = -0.39, 95% CI (-0.83, 0.05), p = 0.08}, {SMD = -0.40, 95% CI (-1.07, 0.27), p = 0.25}, respectively. Subgroup analyses, grouped by intervention times, showed that six to eight weeks of intervention improved HbA1c compared to the control group (p < 0.05), both six to eight weeks and 12-24 weeks had a better intervention effect on Insulin, and HOMA-IR (p < 0.05).In contrast, there was no statistically significant variation in the length between FBG and BMI regarding duration.ConclusionThis meta-analysis found probiotics at different intervention times play a positive role in modulating glucose in T2DM, specifically for HbA1c in six to eight weeks, Insulin and HOMA-IR in six to eight weeks, and 12-24 weeks. To confirm our findings, further excellent large-sample research is still required.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023483325.

Objectives Investigate the impact of daily occupational walking steps on the progression of papillary thyroid cancer (PTC), a topic hitherto underresearched. Material and Methods The authors analyzed the data from 800 individuals with PTC across stages 0–IV. Participants were evenly divided into 2 distinct occupational groups: office workers and construction workers (N = 400 each). Data included comprehensive records of daily walking steps, demographic information, and clinical indicators. Pearson’s correlation coefficients or analysis of variance (ANOVA) were employed to assess the linkage between daily walking steps and PTC risk and stage, as well as associated biochemical markers. Results The analysis revealed a significant inverse relationship between daily walking steps and PTC risk. A higher frequency of daily steps was associated with reduced chances of PTC onset and a lower diagnostic stage of the disease. This protective effect of physical activity was particularly pronounced in the construc- tion worker cohort. Subsequent evaluations showed that construction workers who consistently logged higher daily steps had markedly lower levels of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody, and thy- roglobulin (Tg). Notably, daily walking steps exhibited a strong inverse correlation with body mass index (BMI), age, PTC volumes, and levels of TSH and Tg across both occupational groups (ρ < –0.37). The increase in daily steps was associated with the reduction in PTC stages (p < 0.001). Conclusions The research underscores the potential benefits of increased daily walking steps, suggesting that they may play a protective role in reducing PTC risk and moderating its progression. Int J Occup Med Environ Health. 2024;37(1):58–71

Currently, commercial cellular public networks such as 4G/5G have been widely deployed in China. In addition to serving general public customers, they are extensively used in the electric power industry for electricity information acquisition and distribution automation telemetry, as well as other non-control-related businesses. Simultaneously, power grid companies are actively studying and deploying electric power wireless private networks for bearing high-security control-related businesses such as distribution grid dispatching and distributed energy control. Electric power wireless private networks utilize dedicated spectrum resources, which operate on narrow individual carrier channels with numerous carriers in a discrete manner. These spectral characteristics indicate that electric power wireless private networks require unique system designs that are different from those of commercial cellular networks. Although some proposals have been proposed in relevant research, a unified and mature technical specification for electric power wireless private networks has not yet been established. This paper introduces the development history of electric power wireless private networks and power grid business requirements, with a specific emphasis on system design and key technologies, including frame structure and numerology, massive discrete carrier aggregation, spectrum sensing, security and isolation. We presented a comprehensive analysis and suggestions for these key technologies. Finally, we discuss future research on technological evolution. This study offers indications for an electric power wireless private network ecosystem.

Chinese shrimps are popular among consumers for their delicious taste and high nutritional value, but they are highly susceptible to deterioration due to microbial contamination with degradation of texture, color and flavor. The aim of this study was to evaluate the effects of available chlorine concentration (ACC), processing time and material-liquid ratio on the bacterial inhibition rate of shrimp treated with slightly acidic electrolyzed water (SAEW). The effective parameters were optimized by response surface methodology to the optimal bactericidal conditions: ACC 88 mg/L, processing time 12 min, and material-liquid ratio 1:4. The actual bactericidal inhibition rate of shrimp under these conditions was 37.60 %. On this basis, the quality, color difference and textural changes of shrimp treated with SAEW, sodium hypochlorite and alkaline electrolytic water were compared and investigated during storage at 4 °C. The combined results showed that the SAEW treatment could extend the shelf-life by more than 2 d.

Abstract Purpose To develop a comprehensive multi-classification model that combines radiomics and clinic-radiological features to accurately predict the invasiveness and differentiation of pulmonary adenocarcinoma nodules. Methods A retrospective analysis was conducted on a cohort comprising 500 patients diagnosed with lung adenocarcinoma between January 2020 and December 2022. The dataset included preoperative CT images and histological reports of adenocarcinoma in situ (AIS, n = 97), minimally invasive adenocarcinoma (MIA, n = 139), and invasive adenocarcinoma (IAC, n = 264) with well-differentiated (WIAC, n = 99), moderately differentiated (MIAC, n = 84), and poorly differentiated IAC (PIAC, n = 81). The patients were classified into two groups (IAC and non-IAC) for binary classification and further divided into three and five groups for multi-classification. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) algorithm to identify the most informative radiomics and clinic-radiological features. Eight machine learning (ML) models were developed using these features, and their performance was evaluated using accuracy (ACC) and the area under the receiver-operating characteristic curve (AUC). Results The combined model, utilizing the support vector machine (SVM) algorithm, demonstrated improved performance in the testing cohort, achieving an AUC of 0.942 and an ACC of 0.894 for the two-classification task. For the three- and five-classification tasks, the combined model employing the one versus one strategy of SVM (SVM-OVO) outperformed other models, with ACC values of 0.767 and 0.607, respectively. The AUC values for histological subtypes ranged from 0.787 to 0.929 in the testing cohort, while the Macro-AUC and Micro-AUC of the multi-classification models ranged from 0.858 to 0.896. Conclusions A multi-classification radiomics model combined with clinic-radiological features, using the SVM-OVO algorithm, holds promise for accurately predicting the histological characteristics of pulmonary adenocarcinoma nodules, which contributes to personalized treatment strategies for patients with lung adenocarcinoma.

Abstract Background Primary adrenal lymphoma (PAL) is a rare disease confined wholly or chiefly to extramural involvement. Tumor thrombus in the central adrenal vein, renal vein, and inferior vena cava has been reported in adrenal pheochromocytoma, adrenocortical carcinoma, adrenal metastasis carcinoma, and adrenal leiomyosarcoma. Primary adrenal diffuse large B cell lymphoma with tumor thrombus in the central adrenal vein has rarely been reported in the current study. ( We searched in PubMed, Web of Science databases, Embase, and Medline in the English language from 1970 to December 2022. The keywords used were “Primary adrenal lymphoma " and " tumor thrombus”.) Case presentation In this report, we discuss the case of a 57-year-old woman who complained of abdominal discomfort following cold stimulation, low back pain, anorexia, fatigue, and weight loss for 1 year. Contrast-enhanced spiral computed tomography (CT) showed mild-to-moderate enhancement of the bilateral masses and central adrenal vein tumor thrombus. After an exhaustive study, the patient was diagnosed with primary adrenal diffuse large B-cell lymphoma. In the diagnosis of PAL, the possibility of a tumor embolism in the central adrenal vein, renal vein, or inferior vena cava should be considered, although this is rare.

Marigold (Tagetes erecta) has a capitulum with two floret types: sterile ray florets and fertile disc florets. This distinction makes marigold a valuable model for studying floral organ development in Asteraceae, where MADS-box transcription factors play crucial roles. Here, 65 MADS-box genes were identified in the marigold genome, distributed across all 12 chromosomes. These genes were classified into type I (13 genes) and type II (52 genes) according to phylogenetic relationships. The gene structure of type I was simpler than that of type II, with fewer conserved motifs. Type I was further divided into three subclasses, Mα (8 genes), Mβ (2 genes), and Mγ (3 genes), while type II was divided into two groups: MIKCC (50 genes) and MIKC* (2 genes), with MIKCC comprising 13 subfamilies. Many type II MADS-box genes had evolutionarily conserved functions in marigold. Expression analysis of type II genes across different organs revealed organ-specific patterns, identifying 34 genes related to flower organ development. Given the distinct characteristics of the two floret types, four genes were specifically expressed only in the petals of one floret type, while twenty genes were expressed in the stamens of disc florets. These genes might have been related to the formation of different floret types. Our research provided a comprehensive and systematic analysis of the marigold MADS-box genes and laid the foundation for further studies on the roles of MADS-box genes in floral organ development in Asteraceae.

Coccidioidomycosis is a fungal infection commonly found in the tropical regions of southwestern United States, such as Arizona, the Central Valley of California, parts of New Mexico, and western Texas. The endemic regions also extend into northern Mexico and include focal endemic areas in sections of Central America and Argentina. Coccidioides species have also been reported in central and southern Utah, Nevada, and the central part of Washington State., the pathogenic bacteria commonly colonize the lungs. China, which is outside the traditionally established endemic area, is witnessing a rise in reported cases of pulmonary coccidioidomycosis. Meanwhile, the comorbidities of the disease began to become complicated. We reported two Chinese patients with pulmonary coccidioidomycosis complicated by organizing pneumonia and reviewed 42 cases of Chinese patients in the literature from 1958 to 2024. Out of the 44 patients from 13 different provinces (Including Hong Kong Special Administrative Region and Taiwan), the average age was (43.08 ± 3.03) years. Among them, 34 (76.7 %) were male, while 10 (23.3 %) were female, cough/sputum (81.8 %) are the most common symptoms, the cases are concentrated in coastal areas. 27(61.4 %) were Imported and 17(38.6 %) were domestic primary cases, showing a higher proportion of imported cases compared to domestic primary cases. Misdiagnosis and mistreatment have a significant impact on patients, the combination of new technologies and traditional pathology diagnosis have substantially promoted precise diagnosis for clinician in non-endemic areas. Interestingly, the histopathological findings of the two patients we report showed evident organizing pneumonia and an increased eosinophil count, the application of corticosteroid drugs notably improved the patients' conditions. Overall, at least 84.1 % of patients had a favorable prognosis. Considering the changing epidemiology of pulmonary coccidioidomycosis, Chinese healthcare providers should be cautious about their patients' travel history, particularly among male individuals.

We have developed an intermolecular aminothiolation of simple olefins using Bunte salt as a thiolating agent. This protocol produces thiyl free radicals under PIDA oxidation conditions, eliminating the need for transition-metal catalysts. The method has a wide range of substrate applicability and is suitable for large-scale preparation and late-stage modification of drug molecules.

Abstract Background Radiotherapy is widely applied in breast cancer treatment, while radiotherapy resistance is inevitable. TGF-β1 has been considered to be an endogenous factor for the development of radiotherapy resistance. As a large portion of TGF-β1 is secreted in an extracellular vesicles-associated form (TGF-β1EV), particularly in radiated tumors. Thus, the understanding of the regulation mechanisms and the immunosuppressive functions of TGF-β1EV will pave a way for overcoming the radiotherapy resistance in cancer treatment. Methods The superoxide-Zinc-PKC-ζ-TGF-β1EV pathway in breast cancer cells was identified through sequence alignments of different PKC isoforms, speculation and experimental confirmation. A series of functional and molecular studies were performed by quantitative real-time PCR, western blot and flow cytometry analysis. Mice survival and tumor growth were recorded. Student’s t test or two-way ANOVA with correction was used for comparisons of groups. Results The radiotherapy resulted in an increased expression of the intratumoral TGF-β1 and an enhanced infiltration of the Tregs in the breast cancer tissues. The intratumoral TGF-β1 was found mainly in the extracellular vesicles associated form both in the murine breast cancer model and in the human lung cancer tissues. Furthermore, radiation induced more TGF-β1EV secretion and higher percentage of Tregs by promoting the expression and phosphorylation of protein kinase C zeta (PKC-ζ). Importantly, we found that naringenin rather than 1D11 significantly improved radiotherapy efficacy with less side effects. Distinct from TGF-β1 neutralizing antibody 1D11, the mechanism of naringenin was to downregulate the radiation-activated superoxide-Zinc-PKC-ζ-TGF-β1EV pathway. Conclusions The superoxide-zinc-PKC-ζ-TGF-β1EV release pathway was elucidated to induce the accumulation of Tregs, resulting in radiotherapy resistance in the TME. Therefore, targeting PKC-ζ to counteract TGF-β1EV function could represent a novel strategy to overcome radiotherapy resistance in the treatment of breast cancer or other cancers. Trial registration: The using of patient tissues with malignant Non-Small Cell Lung Cancer (NSCLC) was approved by the ethics committees at Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (NCC2022C-702, from June 8th, 2022).

Abstract In vivo experimental analysis of human brain tissue poses substantial challenges and ethical concerns. To address this problem, we developed a computational method called the Brain Gene Expression and Network-Imputation Engine (BrainGENIE) that leverages peripheral-blood transcriptomes to predict brain tissue-specific gene-expression levels. Paired blood–brain transcriptomic data collected by the Genotype-Tissue Expression (GTEx) Project was used to train BrainGENIE models to predict gene-expression levels in ten distinct brain regions using whole-blood gene-expression profiles. The performance of BrainGENIE was compared to PrediXcan, a popular method for imputing gene expression levels from genotypes. BrainGENIE significantly predicted brain tissue-specific expression levels for 2947–11,816 genes (false-discovery rate-adjusted p

This work aims to expand the understanding on the nature of institutional innovation and the goal of knowledge innovation of intellectual property (IP) law in the era of big data (BD) and to avoid the risks of information security in the IP service system. On the basis of the era of BD, the nature of institutional innovation and the goal of knowledge innovation in IP law are systematically discussed. Combined with smart contract (SC) technology, an IP service system based on blockchain technology is designed to ensure the security of IP services. The SC is optimized from the perspective of concurrency, and the contract transactions (CTs) are clustered. Moreover, considering the execution time (ET) and available resources of CTs, a speculative concurrency control algorithm that can realize intelligent contract scheduling is proposed. On the basis of the ciphertext-policy attribute-based encryption (CP-ABE) algorithm, a policy-updatable attribute encryption algorithm is designed. The improved CP-ABE algorithm includes six steps: system initialization, attribute private key generation, encryption, decryption, ciphertext policy generation, and ciphertext policy update. The identity parameter of the traceability manager is introduced into the improved CP-ABE scheme, which significantly increases the amount of computation of bilinear mapping, thus resulting in the time cost of encryption and decryption being approximately 350 ms and 300 ms higher than that of the CP-ABE scheme. Using the technical mode of “blockchain + SC,” the design of the IP service system is realized, which has important reference value for the institutional innovation of IP law.

In the field of bioinformatics, the construction of gene regulatory networks is crucial. In recent years, non-homogeneous dynamic Bayesian networks have become a common modeling tool for learning gene regulatory networks from gene expression time-series data. Aiming at this research field, this paper combs the gene regulatory network modeling methods based on homogeneous dynamic Bayesian network, and summarizes the non-homogeneous dynamic Bayesian models proposed in the past ten years from the time slice division method and gene regulation network parameter learning. The main contents include: time slice division method, including free allocation, continuous changepoint process, discrete changepoint process and hidden Markov-based changepoint process; gene regulation network parameter learning, mainly including sequence coupling parameters and global coupling parameters. After that, the performance of the non-homogeneous dynamic Bayesian network models is analyzed, and the accuracy and reliability of these models for gene regulatory network modeling, as well as the differences and connections between the models are introduced. Finally, the difficulties and challenges of gene regulatory network construction and some future research directions of non-homogeneous dynamic Bayesian net-work models are pointed out.

DNA methylation (DNAm) that occurs on promoter regions is primarily considered to repress gene expression. Previous studies indicated that DNAm could also show positive correlations with gene expression. Both DNAm and gene expression profiles are known to be tissue- and development-specific. This study aims to investigate how DNAm and gene expression are coordinated across different human tissues and developmental stages, as well as the biological significance of such correlations. By analyzing 2,239 samples with both DNAm and gene expression data in the same human subjects obtained from six published datasets, we evaluated the correlations between gene and CpG pairs (GCPs) at cis-regions and compared significantly correlated GCPs (cGCPs) across different tissues and brains at different age groups. A total of 37,363 cGCPs was identified in the six datasets; approximately 38% of the cGCPs were positively correlated. The majority (>90%) of cGCPs was tissue- or development-specific. We also observed that the correlation direction can be opposite in different tissues and ages. Further analysis highlights the importance of cGCPs for their cellular functions and potential roles in complex traits and human diseases. For instance, the early developmental brain possessed a highly unique set of cGCPs that were associated with neurogenesis and psychiatric disorders. By assessing the epigenetic factors involved in cGCPs, we discovered novel regulatory mechanisms of positive cGCPs distinct from negative cGCPs, which were related to multiple factors, such as H3K27me3, CTCF, and JARD2. The catalogue of cGCPs compiled can be used to guide functional interpretation of genetic and epigenetic studies.

The 5-minute frequency domain method was used to examine the effects of polysomnography (PSG)-guided acute selective sleep deprivation (REM/SWS) on the cardiovascular autonomic nervous system, heart rate, and rhythm in healthy volunteers to understand the relationship between cardiac neuro regulatory homeostasis and cardiovascular system diseases in healthy subjects. The study included 30 healthy volunteers selected through the randomized-controlled method, randomly divided into REM sleep deprivation and SWS sleep deprivation groups. PSG analyses and dynamic electrocardiogram monitoring were done at night, during slow wave sleep or REM sleep. An all-night sleep paradigm, without any interruptions, was tested 3 times for comparison. The frequency domain parameter method was further used to monitor the volunteers 5 min before and after a period of sleep deprivation. According to the characteristics of the all-night sleep scatter plot, healthy volunteers were divided into abnormal and normal scatter plot groups. When compared with the period before sleep deprivation, high frequency (HF) and normalized high-frequency component (HFnu) were found to be decreased. Normalized low-frequency component (LFnu) increased in the abnormal scatter plot group after sleep deprivation, and this difference was statistically significant (P < 0.05). The scatter plot also showed that very low frequency (VLF) increased only in the normal group after deprivation and this difference, as well, was statistically significant (P < 0.05). The increase in diastolic blood pressure in the abnormal group was statistically significant (P < 0.05), but the change in blood pressure in the normal group was not statistically significant (P > 0.05). There are 62.5% of the patients and 20% of the employees that were observed to have abnormal whole-night sleep patterns during the uninterrupted whole-night sleep regime. Patients with atrial or ventricular premature beats (more than 0.1%), and those with ST-t changes during sleep, were all ascertained as abnormal. We concluded that some healthy people could face unstable autonomic nervous functioning related to their long-term tension, anxiety, time urgency, hostility, and other chronic stress states. In the face of acute sleep deprivation selectivity, mild stress based excitability of the vagus nerve is reduced, which diminishes the protective function, making them susceptible to conditions such as premature ventricular arrhythmia.

Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated 9 (CRISPR/Cas9) system has recently become one popular technology due to its efficiency, precision, and simplicity compared with other genome editing tools such as Zinc Finger Nucleases (ZFNs) and Transcription Activator Like Effector Nucleases (TALENs). Horticultural crops provide energy and health-keeping nutrients to humankind. Genome-editing technology has become widely adopted in horticultural breeding with the increasing demand for high yield and better-quality horticultural crops. Here, we describe the CRISPR/Cas9 system construction, its optimization, including sgRNA promoter, sgRNA design, Cas9 protein promoter, SpCas9 variants and orthologs, and vector delivery methods. We also summarized the application of this technology in horticultural plants for stress responses enhancement, fruit quality improvement, and cultivation traits modification. This detailed review was compiled to help establish comprehensive understanding of the CRISPR/Cas9 systems and provide a reference for further developing this technology to manipulate horticultural plant traits effectively.

Aim: The Shexiang Baoxin Pill (SBP) has been extensively used to treat cardiovascular diseases in China for four decades, and its clinical efficacy has been widely approved. However, the mechanism by which this is achieved remains largely unexplored. Research attempting to understand the underlying mechanism is ongoing, but the findings are controversial. Here, we aimed to explore the possible mechanism of SBP in myocardial ischemia-reperfusion (I/R) injury using heart single-nucleus and spatial ribonucleic acid (RNA) sequencing.Methods: We established a murine myocardial I/R injury model in C57BL/6 mice by ligating and recanalizing the left coronary artery anterior descending branch. Subsequently, single-nucleus RNA-seq and spatial transcriptomics were performed on mice cardiac tissue. We initially assessed the status of cell types and subsets in the model administered with or without SBP.Results: We used single-nucleus RNA sequencing to comprehensively analyze cell types in the cardiac tissue of sham, I/R, and SBP mice. Nine samples from nine individuals were analyzed, and 75,546 cells were obtained. We classified the cells into 28 clusters based on their expression characteristics and annotated them into seven cell types: cardiomyocytes, endothelial cells, fibroblasts, myeloid cells, smooth muscle cells, B cells, and T cells. The SBP group had distinct cellular compositions and features than the I/R group. Furthermore, SBP-induced cardioprotection against I/R was associated with enhanced cardiac contractility, reduced endocardial cell injury, increased endocardial-mediated angiogenesis, and inhibited fibroblast proliferation. In addition, macrophages had active properties.Conclusion: SBP improves the early LVEF of I/R mice and has a cardioprotective effect. Through sequencing analysis, we observed that SBP can increase the gene expression of Nppb and Npr3 in the infarct area of the heart. Npr3 is related to vascular generation mediated by endocardial cells and requires further research. In addition, SBP increases the number of fibroblasts, inhibits the expression of genes related to fibroblast activation and proliferation, and increases the transformation of endothelial cells into fibroblasts. These findings will help to indicate directions for further research.

Abstract Nanofiller reinforcement is an effective method to prepare high thermally conductive polymer‐matrix composites. However, the poor dispersion of nanofillers and high interfacial thermal resistance between the filler and matrix seriously affect the thermal conductivity and mechanical properties of composites. To solve this problem, a small amount of conjugated fluorene group is introduced into the polymer chain of poly (ether ether ketone) (PEEK) to afford the fluorene‐functionalized copolymer matrix (FD‐PEEK). In an in situ polymerization procedure, the matrix non‐covalently binds to multi‐walled carbon nanotubes (MWCNT) to allow highly filled PEEK/MWCNT nanocomposites. With the filler dispersion and matrix–filler interfacial bonding improved, the prepared nanocomposites possess both high thermal conductivity and tensile strength. At the optimal ratio of 2 mol% fluorene groups in the polymer chain, the nanocomposite with 10 wt% MWCNT exhibits an excellent thermal conductivity of 2.41 W m−1 K−1, which is 868% higher than pristine PEEK, with tensile strength remaining 104.3 MPa. The PEEK/MWCNT nanocomposites can be further used as matrix resins to build double‐segregated network multi‐component composites, which contributes to an innovative strategy to design high‐performance thermally conductive materials.

A key issue in fishery forecasting is the collection of high-precision subsurface environmental data. A data assimilation method, named gradient-dependent optimal interpolation, was used to construct the near-real-time vertical temperature and salinity structure of a squid fishery ground based on Argo observations. The results were verified by truth-finding comparisons and applied to analyze the relationship between neon flying squid and the subsurface environment in the Kuroshio–Oyashio Confluence Region. The temperature and salinity differences between the constructed results and survey data were less than ±0.5 °C and ±0.02, respectively. Most of the relative analysis errors were less than the observational errors. Statistical analysis revealed that the most suitable temperature for squid was 18–24 °C at the near-surface (

As natural products with biological activity, the quality of traditional Chinese medicines (TCM) is the key to their clinical application. Fingerprints based on the types and contents of chemical components in TCM are an internationally recognized quality evaluation method but ignore the correlation between chemical components and efficacy. Through chemometric methods, the fingerprints represented by the chemical components of TCM were correlated with its pharmacodynamic activity results to obtain the spectrum–effect relationships of TCM, which can reveal the pharmacodynamic components information related to the pharmacodynamic activity and solve the limitations of segmentation of chemical components and pharmacodynamic research in TCM. In the 20th anniversary of the proposed spectrum–effect relationships, this paper reviews its research progress in the field of TCM, including the establishment of fingerprints, pharmacodynamic evaluation methods, chemometric methods and their practical applications in the field of TCM. Furthermore, the new strategy of spectrum–effect relationships research in recent years was also discussed, and the application prospects of this technology were discussed.

Abnormal gray matter (GM) asymmetry has been verified in autism spectrum disorder (ASD), which is characterized by high heterogeneity. ASD is distinguished by three core symptom domains. Previous neuroimaging studies have offered support for divergent neural substrates of different core symptom domains in ASD. However, no previous study has explored GM asymmetry alterations underlying different core symptom domains. This study sought to clarify atypical GM asymmetry patterns underlying three core symptom domains in ASD with a large sample of 230 minors with ASD (ages 7–18 years) and 274 matched TD controls from the Autism Brain Imaging Data Exchange I (ABIDE I) repository. To this end, the scores of the revised autism diagnostic interview (ADI-R) subscales were normalized for grouping ASD into three core-symptom-defined subgroups: social interaction (SI), verbal communication (VA), and restricted repetitive behaviors (RRB). We investigated core-symptom-related GM asymmetry alterations in ASD resulting from advanced voxel-based morphometry (VBM) by general linear models. We also examined the relationship between GM asymmetry and age and between GM asymmetry and symptom severity assessed by the Autism Diagnostic Observation Schedule (ADOS). We found unique GM asymmetry alterations underlying three core-symptom-defined subgroups in ASD: more rightward asymmetry in the thalamus for SI, less rightward asymmetry in the superior temporal gyrus, anterior cingulate and caudate for VA, and less rightward asymmetry in the middle and inferior frontal gyrus for RRB. Furthermore, the asymmetry indexes in the thalamus were negatively associated with ADOS_SOCIAL scores in the general ASD group. We also showed significant correlations between GM asymmetry and age in ASD and TD individuals. Our results support the theory that each core symptom domain of ASD may have independent etiological and neurobiological underpinnings, which is essential for the interpretation of heterogeneity and the future diagnosis and treatment of ASD.

Anisakidosis is a food-borne parasitic disease (FBPD) caused by the third-stage larvae of the family Anisakidae. Therefore, it is important to develop a simple, rapid and equipment-free detection method for anisakids in fish samples or seafood since current methods are time-consuming and require complex instruments. In this study, a recombinase polymerase amplification (RPA)-based method was established for the first time to detect anisakids by targeting the internal transcribed spacer (ITS) regions. The detection results were visualized by including SYBR Green I (SG) in the method. The sensitivity of RPA-SG assay was 102 copies per reaction of recombinant plasmid (within 20 min at 37°C), similar to quantitative real-time PCR (qPCR). The assay had high specificity for detecting anisakids against other related parasites and host fish. In addition, the assay was further used to detect fresh marine fish contaminated with anisakids and it showed high precision. These results indicate that the novel RPA-SG assay suitable for visual detection of anisakids in the field and food safety control.

Mesoscale eddies are ubiquitous in global oceans yielding significant impacts on marine life. As a short-lived pelagic squid species, the population of neon flying squid (Ommastrephes bartramii) is extremely sensitive to changes in ambient oceanic variables. However, a comprehensive understanding of how mesoscale eddies affect the O. bartramii population in the Northwest Pacific Ocean is still lacking. In this study, a 10-year squid fisheries dataset with eddy tracking and high-resolution reanalysis ocean reanalysis data was used to evaluate the impact of mesoscale eddies and their induced changes in environmental conditions on the abundance and habitat distribution of O. bartramii in the Northwest Pacific Ocean. A weighted-based habitat suitability index (HSI) model was developed with three crucial environmental factors: sea surface temperature (SST), seawater temperature at 50-m depth (T50m), and chlorophyll-a concentration (Chl-a). During years with an unstable Kuroshio Extension (KE) state, the abundance of O. bartramii was significantly higher in anticyclonic eddies (AEs) than that in cyclonic eddies (CEs). This difference was well explained by the distribution pattern of suitable habitats in eddies derived from the HSI model. Enlarged ranges of the preferred SST, T50m, and Chl-a for O. bartramii within AEs were the main causes of more squids occurring inside the warm-core eddies, whereas highly productive CEs matching with unfavorable thermal conditions tended to form unsuitable habitats for O. bartramii. Our findings suggest that with an unstable KE background, suitable thermal conditions combined with favorable foraging conditions within AEs were the main drivers that yielded the high abundance of O. bartramii in the warm eddies.

The uneven distribution of water resources in time and space restricts the development of society, which is a universal problem facing the world. To improve the ability to regulate water resources in water diversion projects and alleviate the contradiction between water resources and social development, China has decided to build water network projects (WNPs). A WNP is an integrated water supply system that includes multiple water sources and network water supply lines and integrates the functions of water supply, water delivery, and optimal allocation of water resources into a system that can supply water to many users. An appropriate water pricing mechanism is the key to ensuring the sustainable operation of water network projects. This paper presents a comprehensive water pricing model (WPM) for WNPs. The purpose of this model is to unify the water price measurement standard of WNPs and lay the foundation for water price marketization in the future. By applying the model to the Jiaodong WNP, it is found that the model is expected to improve the unbalanced use of water sources and the large difference in prices at water supply points (WSPs) in the project. This study not only provides a theoretical basis for water pricing reform but also has great potential to improve the efficiency of water resource use.

Abstract Water electrolysis is a sustainable and clean method to produce hydrogen fuel via hydrogen evolution reaction (HER). Using stable, effective and low-cost electrocatalysts for HER to substitute expensive noble metals is highly desired. In this paper, by using first-principles calculation, we designed a defect and N-, S-, P-doped penta-graphene (PG) as a two-dimensional (2D) electrocatalyst for HER, and its stability, electronic properties and catalytic performance were investigated. The Gibbs free energy (ΔG H), which is the best descriptor for the HER, is calculated and optimized, the calculation results show that the ΔG H can be 0 eV with C2 vacancies and P doping at C1 active sites, which should be the optimal performance for a HER catalyst. Moreover, we reveal that the larger charge transfer from PG to H, the closer ΔG H is to zero according to the calculation of the electron charge density differences and Bader charges analysis. Ulteriorly, we demonstrated that the HER performance prefers the Volmer–Heyrovsky mechanism in this study.

Lung adenocarcinoma (LUAD) is a frequently diagnosed malignant tumor that is highly invasive and lethal. The prognosis of patients with LUAD still needs to be improved, as conventional treatment is remarkably well tolerated. In this study, the expression profile of LUAD in the TCGA database was used for differential expression analysis, and differential expression genes were determined to construct a weighted gene co-expression network analysis (WGCNA) for dividing and finding the gene modules with the highest correlation with tumor stage. Here, METTL5, DDX23, GPSM2, CEP95, WDCP, and METL17 were identified as hub genes. According to the relation degree, METTL5 was determined as the candidate gene in this study. Difference analysis and receiver operating characteristic (ROC) curve were applied to identify the predictive performance of METTL5 in LUAD, and Kaplan-Meier (KM) analysis showed that the prognosis of LUAD patients with high METTL5 expression was poor. Further GSEA analysis showed that high-expressed METTL5 was related to epithelial-mesenchymal transition and other pathways. Therefore, METTL5 may be involved in the occurrence and malignant progression of LUAD. The current findings provide an effective molecular target for early diagnosis of LUAD, helping monitor the malignant progression of LUAD and improve the prognosis of LUAD patients.

Synaptic dysfunction is a manifestation of several neurobehavioral and neurological disorders. A major therapeutic challenge lies in uncovering the upstream regulatory factors controlling synaptic processes. Plant homeodomain (PHD) finger proteins are epigenetic readers whose dysfunctions are implicated in neurological disorders. However, the molecular mechanisms linking PHD protein deficits to disease remain unclear. Here, we generated a PHD finger protein 21B–depleted (Phf21b-depleted) mutant CRISPR mouse model (hereafter called Phf21bΔ4/Δ4) to examine Phf21b’s roles in the brain. Phf21bΔ4/Δ4 animals exhibited impaired social memory. In addition, reduced expression of synaptic proteins and impaired long-term potentiation were observed in the Phf21bΔ4/Δ4 hippocampi. Transcriptome profiling revealed differential expression of genes involved in synaptic plasticity processes. Furthermore, we characterized a potentially novel interaction of PHF21B with histone H3 trimethylated lysine 36 (H3K36me3), a histone modification associated with transcriptional activation, and the transcriptional factor CREB. These results establish PHF21B as an important upstream regulator of synaptic plasticity–related genes and a candidate therapeutic target for neurobehavioral dysfunction in mice, with potential applications in human neurological and psychiatric disorders.

Rose is sensitive to high temperature which will make the rose go into a semi-dormancy state. Grafting is an excellent way to enhance rose heat tolerance. Here, heat-tolerant Rosa multiflora ‘Huanong Wuci 1′ (W) and heat-sensitive Rosa chinensis ‘Old Blush’ (X) were selected as experimental materials. The RNA-seq technique was used to investigate the transcriptomes of self-root grafting line (XX0), heterogeneous grafting line (XW0), self-root grafting line under 6 h heat stress (XX6), and heterogeneous grafting line under 6 h heat stress (XW6). Under high temperature stress, multiple signaling pathways were activated, moreover, a large number of transcription factors and functional genes were induced, especially the HSFs and HSPs with remarkably upregulated expression levels. The GO analysis showed that the differences in the expressions of the genes related to fatty acids and carbohydrates were observed between self-root grafting line and heterogeneous grafting line. In addition, 14 P450s were differentially expressed, and one lectin gene was up-regulated in XW0 vs XW6, but down-regulated in XX0 vs XX6. Considering physiological and biochemical traits such as relative electrolyte leakage, SOD activity, proline, and total soluble sugars, DEGs involved in these processes may be key factors to resist high temperature. The present study provides an insight into the complex mechanism underlying grafting in response to heat stress. Our results indicate that grafting is an effective way to improve rose heat resistance.

In this work, a novel P/N flame-retardant monomer (PDHAA) was synthesized through reacting phenyl dichlorophosphate (PDCP) with N-hydroxyethyl acrylamide (HEAA). The structure of PDHAA was confirmed using Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (NMR) spectroscopy. PDHAA monomer and 2-hydroxyethyl methacrylate phosphate (PM-2) monomer were mixed at different mass ratios, to prepare UV-curable coatings, and then applied to the surface of fiber needled felts (FNFs), to improve their flame retardancy. PM-2 was introduced to reduce the curing time of the flame-retardant coatings and improve the adhesion between the coating and the fiber needled felts (FNFs). The research results indicated that the surface flame-retardant FNFs had a high limiting oxygen index (LOI) and rapidly self-extinguished in a horizontal combustion test and passed a UL-94 V-0 test. At the same time, the CO and CO2 emissions were greatly reduced, and the carbon residue rate was increased. In addition, the introduction of the coating improved the mechanical properties of the FNFs. Therefore, this simple and efficient UV-curable surface flame-retardant strategy has broad application prospects in the field of fire protection.

Interferon-γ (IFN-γ) is a critical component of innate immune responses in humans to combat infection by many viruses, including human cytomegalovirus (HCMV). IFN-γ exerts its biological effects by inducing hundreds of IFN-stimulated genes (ISGs). In this study, RNA-seq analyses revealed that HCMV tegument protein UL23 could regulate the expression of many ISGs under IFN-γ treatment or HCMV infection. We further confirmed that among these IFN-γ stimulated genes, individual APOL1 (Apolipoprotein-L1), CMPK2 (Cytidine/uridine monophosphate kinase 2), and LGALS9 (Galectin-9) could inhibit HCMV replication. Moreover, these three proteins exhibited a synergistic effect on HCMV replication. UL23-deficient HCMV mutants induced higher expression of APOL1, CMPK2, and LGALS9, and exhibited lower viral titers in IFN-γ treated cells compared with parental viruses expressing full functional UL23. Thus, UL23 appears to resist the antiviral effect of IFN-γ by downregulating the expression of APOL1, CMPK2, and LGALS9. This study highlights the roles of HCMV UL23 in facilitating viral immune escape from IFN-γ responses by specifically downregulating these ISGs.

Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota-dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by Burkholderia spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin sensitivity. Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA from tryptophan and indicate that 5-HIAA might alleviate the pathogenesis of T2D. [ABSTRACT FROM AUTHOR]

Abstract Background Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Methods Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. Results GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. Conclusions GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Zhang et al. use mouse tumor models to show that the optimum treatment regime for Treg-induced radiation resistance is vaccine administration followed by radiation therapy. This finding could inform the design of future combinatorial cancer therapies in the clinic.

Two lactic acid bacteria (LAB) strains of Lactobacillus plantarum 21802 and Lactobacillus brevis 6239 were selected and combined for fermentation of grape juice. The changes of sugars, organic acids, volatiles, phenolic compounds as well as antioxidant capacity of the grape juice were characterized. Results showed that fermentation with LAB led to a slight decrease in sugar content and increased in organic acid content. The sugars were mainly consumed at the initial stage of fermentation, while the malic acid was consumed completely during the fermentation. The contents of total phenolics and flavonoids in grape juice decreased gradually during the fermentation process. As compared with the initial contents in unfermented grape juice, the contents of proanthocyanin B2, rutin, isoquercitrin, rhamnose-3-O-glucoside in the final fermented grape juice were increased by 26.83%, 249.24%, 138.48%, 139.60%, respectively, while the contents of gallic acid, proanthocyanin B1, catechin and epicatechin were decreased by 24.49%, 14.85%, 71.68%, 42.52%, respectively. The mice fed with the fermented grape juice showed higher activity of superoxide dismutase and lower level of malondialdehyde both in serum and liver tissue than those fed with the unfermented grape juice. Fermentation with LAB also enhanced the flavor profile by increasing the total number and content of volatile compounds, especially those of monoterpene alcohols, which are the main and characteristic aroma volatile compounds in Muscat aroma grapes. This research confirmed that fermentation with LAB might be a desirable option for improving the flavor and nutritional attributes of grape juice by altering the ratio of sugar to organic acid, improving the phenolic compounds, enhancing the antioxidant capacity, intensifying of the characteristic aroma and pleasant flavor of the grape juice.

With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4.

The multicopy suppressor of IRA (MSI) is a subfamily of WD40 repeat proteins, which is widely involved in plant growth and development. In order to explore the function of MdMSI members in abiotic stress, we identified eight MSI gene family members from the Malus × domestica reference genome. They were distributed on six chromosomes, and they had similar secondary and tertiary structures. We found a variety of regulatory elements in response to hormones and abiotic stress in MdMSI promoters. Through qRT-PCR analysis, it was revealed that MdMSIs were expressed in all tissues, especially in roots. The analysis results also revealed that the expression of MdMSIs was induced in varying degrees under salt, drought stress, and ABA treatments. Furthermore, we obtained the overexpression of MdMSI1-1 transgenic apple calli and Arabidopsis. The overexpression of MdMSI1-1 in calli and Arabidopsis played a negative regulatory role in salt stress response. Our work laid a foundation for further verifying the function of MSI genes under abiotic stress in apples.

Abstract Background AGAMOUS (AG) subfamily genes regulate the floral organs initiation and development, fruit and seed development. At present, there has been insufficient study of the function of AG subfamily genes in Asteraceae. Marigold (Tagetes erecta) belongs to Asteraceae family whose unique inflorescence structure makes it an important research target for understanding floral organ development in plants. Results Four AG subfamily genes of marigold were isolated and phylogenetically grouped into class C (TeAG1 and TeAG2) and class D (TeAGL11–1 and TeAGL11–2) genes. Expression profile analysis demonstrated that these four genes were highly expressed in reproductive organs of marigold. Subcellular localization analysis suggested that all these four proteins were located in the nucleus. Protein-protein interactions analysis indicated that class C proteins had a wider interaction manner than class D proteins. Function analysis of ectopic expression in Arabidopsis thaliana revealed that TeAG1 displayed a C function specifying the stamen identity and carpel identity, and that TeAGL11–1 exhibited a D function regulating seed development and petal development. In addition, overexpression of both TeAG1 and TeAGL11–1 leaded to curling rosette leaf and early flowering in Arabidopsis thaliana. Conclusions This study provides an insight into molecular mechanism of AG subfamily genes in Asteraceae species and technical support for improvement of several floral traits.

The physicochemical properties, organic acid, and phenolic profiles of hawthorn wines prepared by different pretreatments were analyzed. It was found that fermentation together with smashed seeds was favorable for ethanol production, while thermal maceration, addition of pectinase and amyloglucosidase significantly increased the levels of sugar-free extract, residual sugar, total phenolics, flavonoids, and most individual phenolic comounds, showing beneficial effects on improving nutritive value of hawthorn wine. Addition of pectinase and amyloglucosidase caused an increase of methanol content by 34.88% and 26.97%, respectively, while thermal maceration decrease the methanol content by 36.20%. Addition of amyloglucosidase yielded the highest contents of procyanidins as well as flavanols, while thermal maceration and addition of pectinase were favorable for improving phenolic acid level. All the pretreatments significantly increased the contents of succinic acid and malic acid in the final wines, among which thermal maceration and addition of pectinase yielded the highest content of succinic acid and malic acid respectively.

Background To compare the efficiency and toxicity of bevacizumab by intrapleural or intravenous infusion in the management of malignant pleural effusion in patients with non‐small‐cell lung cancer (NSCLC). Methods Sensitizing mutation negative NSCLC patients with malignant pleural effusion were randomized into two groups in 1:1 ratio. The pleural effusion was completely drained in 24 hours; one group received intrapleural infusion and the second group received intravenous infusion of bevacizumab at a dose of 7.5 mg per kg bodyweight. The serum vascular endothelial growth factor (VEGF) was tested before and 72 hours after injection of bevacizumab. Computerized tomography (CT) scan to evaluate pleural effusions was carried out at four weeks for each patient and their survival followed‐up. Results A total of 67 patients were screened and 43 enrolled into the study. The response rate was 80% (16 of 20) in the intrapleural group and 66.7% (14 of 21) in the intravenous group. The median duration of response (DoR) of pleural effusion was 4.50 months and 3.70 months, respectively. The median serum VEGF level at 72 hours decreased 67.25% in the intrapleural group and 57.19% in the intravenous group compared to baseline level (P = 0.276). The median serum VEGF level at 72 hours decreased 52.02% compared to baseline level in patients’ DoR less than three months and 68.33% in patients' DoR longer than three months, respectively (P = 0.014). The main side effects noted were mild to moderate hypertension, proteinuria and epistaxis. Conclusions Bevacizumab intrapleural infusion had higher efficiency and higher safety than intravenous infusion in the management of malignant pleural effusion caused by NSCLC. The decreased level of serum VEGF at 72 hours after bevacizumab treatment was closely related to the response rate and duration of the response of pleural effusion.

PurposeMedical imaging examination is the primary method of diagnosis, treatment, and prevention of cancer. However, the amount of medical image data is often not enough to meet deep learning needs. This article aims to expand the small data set in tumor segmentation based on the deep learning method.MethodsThis method includes three main parts: image cutting and mirroring augmentation, segmentation of augmented images, and boundary reconstruction. Firstly, the image is divided into four parts horizontally & vertically, and diagonally along the tumor’s approximate center. Then each part is mirrored to get a new image and hence a four times data set. Next, the deep learning network trains the augmented data and gets the corresponding segmentation model. Finally, the segmentation boundary of the original tumor is obtained by boundary compensation and reconstruction.ResultsCombined with Mask-RCNN and U-Net, this study carried out experiments on a public breast ultrasound data set. The results show that the dice similarity coefficient (DSC) value obtained by horizontal and vertical cutting and mirroring augmentation and boundary reconstruction improved by 9.66% and 12.43% compared with no data augmentation. Moreover, the DSC obtained by diagonal cutting and mirroring augmentation and boundary reconstruction method improved by 9.46% and 13.74% compared with no data augmentation. Compared with data augmentation methods (cropping, rotating, and mirroring), this method’s DSC improved by 4.92% and 12.23% on Mask-RCNN and U-Net.ConclusionCompared with the traditional methods, the proposed data augmentation method has better performance in single tumor segmentation.