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Abstract Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer’s disease model, we demonstrate silencing of mutant APP swe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.

Participating in megaproject experimental tasks would significantly improve the laboratories’ industry influence and future competitiveness. Thus, this paper introduces the long-term reputation effects of the incentive model of an experimental resource-sharing platform for megaprojects, which could motivate them to consider future benefits and improve their current efforts. The aim is to incentivize laboratories’ resource-sharing behavior more effectively and to increase the amount of resources shared by these laboratories on the platform, thus guaranteeing the long-term sustainability of the platform. It constructs the incentive model by combining dual implicit and explicit incentive mechanisms. It analyses the incentive mechanism of a reputation effect on laboratories compared with the pure explicit mechanism so that the primary conditions for reputation incentives can be obtained to achieve Pareto improvement. Finally, the proposed method is validated in combination with data simulation. The results show that although dual implicit and explicit incentive mechanisms could reduce the information asymmetry between the two sides and increase the efforts of laboratories and the benefits of the platform, the platform should not blindly increase the intensity of these incentives and need to consider the influence of the subsidies of these laboratories’ upfront inputs, the degree of sharing and their informatization capabilities.

Agricultural Jiaosu is rich in nutrients and plant-beneficial microbial communities, and thus has great potential in reducing fertilizer dosage and improving fertilizer use efficiency. This pot experiment was conducted to investigate the effects of agricultural Jiaosu on the growth and yield of rice. The experiment employed three agricultural Jiaosu treatments (i.e., soil solid agricultural Jiaosu, soil liquid agricultural Jiaosu, leaf liquid agricultural Jiaosu) in various combinations, along with one control treatment (chemical fertilizer). Results revealed that plant height of rive agricultural Jiaosu treatments were higher than that of the control treatment, with the ranks as follows: JT (soil solid agricultural Jiaosu + soil liquid agricultural Jiaosu), JY (soil solid agricultural Jiaosu + leaf liquid agricultural Jiaosu), JA (soil solid agricultural Jiaosu + soil liquid agricultural Jiaosu + leaf liquid agricultural Jiaosu) and F (conventional fertilizer) during harvest. The ratio of panicle biomass to total biomass and straw of three types of Jiaosu treatments was significantly higher than that in the chemical fertilizer treatment, indicating that agricultural Jiaosu treatment altered the dry matter distribution characteristics of rice. The yield per plant of JA treatment (49.35 ± 2.43 g) was 8.51% higher than chemical fertilizer treatment. Additionally, the correlation between soil nutrients and plant growth and yield analysis indicated that agricultural Jiaosu has higher nutrient use efficiency with lower input of N, P, and K. The study highlights the potential function of agricultural Jiaosu in promoting crop growth and yields while reducing the need for fertilization.

Introduction: Thromboembolism is a recognized complication of nephrotic syndrome (NS). Evidence supporting the use of rivaroxaban to prevent NS-related thrombosis is limited and controversial. This study aimed to explore the impact of NS on rivaroxaban pharmacokinetics and to collect observational data on the efficacy and safety of rivaroxaban as primary thromboprophylaxis in patients with NS. Methods: This prospective study analyzed 141 patients with NS who received rivaroxaban (10 mg/day) for thromboprophylaxis. High-performance liquid chromatography-tandem mass spectrometry was used to measure the trough and peak plasma concentrations (Ctrough and Cmax) of rivaroxaban. The influence of clinical and genetic factors on these concentrations was examined using multivariate logistic regression. Results: The median Cmax and Ctrough were 68.5 ng/mL (interquartile range [IQR], 31.7–105.5 ng/mL) and 4.4 ng/mL (IQR, 1.2–11.9 ng/mL), respectively. The incidence of thromboembolic events (TEs) was 12.8%, while that of bleeding events was 14.2%, although all were classified as minor. Albumin level was the most significant factor affecting Cmax (ρ = 0.55; p < 0.001) and was also significantly associated with TEs (0.81; 0.71–0.91 per 1.0 g/dL increase; p = 0.001) and bleeding risks (1.11; 1.03–1.19 per 1.0 g/dL increase; p = 0.008). Single nucleotide polymorphisms in the ABCB1 gene significantly influenced Ctrough but were not associated with clinical outcomes. Conclusion: Hypoalbuminemia significantly affects the pharmacokinetics of rivaroxaban in NS patients. A dose-adjustment strategy based on rivaroxaban concentrations, accounting for variable albumin levels, may improve the safety and efficacy of thromboprophylaxis in this population.

Many patients with diabetes are suffering with chronic wounds due to their slow and disorganized healing process, which even lead to serious consequences such as amputation. Nowadays, extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) offer a potential strategy for chronic wound healing, whereas the rapid diffusion and degradation of MSC-EVs hampers the efficacy of wound repair. Herein, we proposed a novel MOF-based hydrogel by cross-linking hyaluronic acid (HA) with UiO-66-NH2 (U6N). The HA-U6N hydrogel could be prepared rapidly with stable character, while the EVs affinity property of U6N was maintained well. This hydrogel allowed us enriching EVs conveniently and rapidly from cell supernatant. The U6N-based hyaluronic acid hydrogel with enriched EVs (HA-U6N-EVs) could markedly accelerate diabetic wound healing efficacy in rats attributing to the sustained release of EVs. Besides, we further showed the miRNAs in MSC-EVs involving in wound healing remained high abundance over 10 days, also demonstrating the superb sustained EVs delivery of HA-U6N hydrogels.

Abstract Currently, organic solvents are necessary for the preparation of anionic liposomes for siRNA delivery. The removal of organic solvent is time‐consuming and the residual organic solvent is not only a hidden danger, but also affects the stability of anionic liposomes. Glycerol, which is physiologically compatible and does not need to be removed, is used to promote the dispersion of lipids and the formation of anionic liposomes. Additionally, the preparation process is simple and not time‐consuming. The results showed that anionic liposomes, which were typically spherical with a particle size of 188.9 nm were successfully prepared with glycerol. And with the help of Ca2+, siRNA was encapsulated in anionic liposomes. The highest encapsulation efficiency at 2.4 mM Ca2+ reached 91%. And the formation of calcium phosphate could promote the endosomal escape of siRNA effectively. The results from cell viability showed that the anionic liposomes had no obvious cytotoxicity. It was also verified that anionic liposomes could improve the resistance of siRNA against degradation. Additionally, siRNA delivered by anionic liposomes could play an effective role in knockout. Therefore, anionic liposomes prepared with glycerol will be a safe and effective delivery platform for siRNA and even other nucleic acid drugs.

Abstract Single nucleotide polymorphism (SNP) typing is crucial for drug dosage and disease progression. Therefore, a simple and convenient genotyping assay is essential for personalised medicine. Herein, we developed a non‐invasive, closed‐tube, and visualised method for genotyping. In this method, oral swabs were lysed to directly perform PCR coupled with nested invasive reaction and visualisation based on gold nanoparticle probes in a closed tube. The strategy for genotyping assay depends on the single base recognition property of invasive reaction. This assay allowed quick and simple sample preparation and the detection of 25 copies/μL of CYP2C19*2 and 100 copies/μL of CYP2C19*3 within 90 min. Further, 20 oral swab samples for CYP2C19*2 and CYP2C19*3 were correctly typed, which agreed with pyrosequencing, indicating that this method has great potential for SNP typing in source‐limited regions to guide personalised medicine.

Abstract Background Characterization of early breast cancer circulating tumor cells (CTCs) may provide valuable information on tumor metastasis. Methods We used immunomagnetic nanospheres to capture CTCs from the peripheral blood of eight early breast cancer patients and then performed single‐cell RNA sequencing using our proposed bead‐dd‐seq method. Results CTCs displayed obvious tumor cell characteristics, such as the activation of oxidative stress, proliferation, and promotion of metastasis. CTCs were clustered into two subtypes significantly correlated with the lymph node metastasis status of patients. CTCs in subtype 1 showed a strong metastatic ability because these CTCs have the phenotype of partial epithelial‐mesenchymal transition and enriched transcripts, indicating breast cancer responsiveness and proliferation. Furthermore, DNA damage repair pathways were significantly upregulated in subtype 1. We performed in vitro and in vivo investigations, and found that cellular oxidative stress and further DNA damage existed in CTCs. The activated DNA damage repair pathway in CTCs favors resistance to cisplatin. A checkpoint kinase 1 inhibitor sensitized CTCs to cisplatin in mouse models of breast cancer metastasis. Conclusion The present study dissects the molecular characteristics of CTCs from early‐stage breast cancer, providing novel insight into the understanding of CTC behavior in breast cancer metastasis.

Abstract The fully insulated busbar system, which has been extensively used in the industry, contains a large number of joints due to its limited length, and thus it is prone to overheating failure caused by poor contact. Taking the uncertainty of contact resistance into account, this paper presents an indirect approach to monitor the conductor temperature for the fully insulated busbar prefabricated joint using the busbar surface temperatures. The model is composed of radial direction temperature calculation (RDTC) in the busbar and axial direction temperature calculation (ADTC) in the conductor. The equivalent thermal resistance of joint is defined to characterize the influence of contact resistance, based on which RDTC and ADTC are corrected by an iterative method. The temperature rise test of the prefabricated joint was carried out. When the contact state is normal, the transient and steady‐state error is within 4 and 1 K, respectively. When the contact state is abnormal, the steady‐state error under rated current is less than 5 K, and the transient error with the step load is about 10 K, which is thoroughly analyzed. From an engineering point of view, the proposed algorithm can effectively monitor the joint hotspot temperature and evaluate the contact state.

No current RNA-targeted interference tools have been reported to simultaneously up and down-regulate different gene expressions. Here we characterized an RNA-targeted genetic regulatory strategy composed of a flap endonuclease 1 (FEN1) and specific mis-hairpin DNA probes (mis-hpDNA), to realize the orthogonal genetic regulation. By targeting mRNA, the strategy hindered the translation and silenced genes in human cells with efficiencies of ~60%. By targeting miRNA, the strategy prevented the combination of miRNA to its specific mRNA and increased this mRNA expression by about 3-folds. In combination, we simultaneously performed CXCR4 gene knock-down (~50%) and EGFR gene activation (1.5-folds) in human cells. Although the functional property can be further improved, this RNA-targeted orthogonal genetic regulating strategy is complementary to classical tools.

With the development of offshore wind power development to deep and far sea, offshore flexible low-frequency AC (LFAC) transmission technology has attracted more and more attention from academia and industry in recent years. The control and protection system is the brain of flexible LFAC transmission, which is directly related to the performance, safety and benefit of LFAC transmission. In order to improve its operation reliability and limit the impact caused by any control link fault, in this paper, the control system is divided into system level control strategy, converter station level control strategy and valve level control strategy, which is from high level to low level according to the stratification principle. For the protection system, a specific zoning protection scheme is proposed. Finally, a two-terminal flexible LFAC transmission system is built in PSCAD/EMTDC. The simulation results prove the validity and correctness of the proposed control and protection strategy.

Summary Numerous viral outbreaks have threatened us throughout history. Here, we demonstrated a nucleic acid‐based antiviral strategy named AntiV‐SGN. Unlike those CRISPR‐mediated methods, AntiV‐SGN has advantages of no targets' sequence limitation, such as protospacer adjacent motif (PAM) or protospacer flanking sequence (PFS), being universal for both DNA and RNA viruses. AntiV‐SGN was composed of a FEN1 protein and specific hpDNAs targeting viruses' nucleic acid. Its antiviral ability was tested on SARS‐CoV‐2 and HBV respectively. Reporter assays in human cells first illustrated the feasibility of AntiV‐SGN. Then, it was verified that AntiV‐SGN destroyed about 50% of live RNAs of SARS‐CoV‐2 in Vero cells and 90% cccDNA of HBV in HepG2.2.15 cells. It was also able to remove viral DNA integrated into the host's genome. In the mouse model, AntiV‐SGN can be used to significantly reduce HBV expression at a level of 90%. Actually, in some cases, when viruses mutate to eliminate PAM/PFS or hosts were infected by both DNA and RNA viruses, AntiV‐SGN could be a choice. Collectively, this study provided a proof‐of‐concept antiviral strategy of AntiV‐SGN, which has potential clinical value for targeting a wide variety of human pathogens, both known and newly identified.

The urban agglomeration in the middle reaches of the Yangtze River holds a crucial strategic position in China’s economic and social development landscape. Exploring the coordinated development effects within the digital economy and innovation in this area is conducive to promoting the development of the central region of China and the Yangtze River Economic Belt. This paper uses the 28 sample cities in urban agglomeration in the middle reaches of the Yangtze River as the study sample, and constructs a digital economy indicator system and an urban innovation efficiency indicator system. Based on the coupling coordination degree model, we use kernel density estimation, the Markov chain algorithm, and the Dagum Gini coefficient decomposition method to empirically investigate the dynamic trends in coupling coordination development between the digital economy and urban innovation efficiency from 2012 to 2021. The research results reveal an overall upward trend in the digital economy, innovation efficiency, and coupling coordination development stages. However, the upward trend is accompanied by the risk of recession. Moreover, there are significant differences between cities, as highlighted by the differences between Wuhan and other cities. In the light of the findings, it is recommended that government departments take measures, including being alert to the risk of regressive development, developing cities in a realistic manner, and drawing on the experiences of outstanding cities in development. This research can provide new insights and empirical references for government entities to take measures for a more coordinated development of the digital economy and innovation efficiency in the urban agglomeration in the middle reaches of the Yangtze River.

ObjectivesThis study proposes a measurement scheme based on the Kalman filtering method for improving efficiency and lowering complexity in measuring the magnetization parameters of shipboard three-component geomagnetic field measurement systems. MethodsThe principles and characteristics of magnetization in the mathematical model of a shipboard three-component geomagnetic field measurement system are studied. The steps for applying the Kalman filtering algorithm are used to compute the ship's magnetization parameters. Then, computer simulation and mockup experiment were conducted to testify its validity. ResultsThe simulation and experiment show that the three-component geomagnetic field can be computed precisely, and the algorithm performs well in convergence with a small sampling of data. ConclusionsTherefore, the Kalman filtering method has higher efficiency and lower cost in the practice of measuring a ship's magnetization parameters.

With the development of active distribution network (ADN), the situation that multiple users such as distributed generations and loads are connected to multiple nodes of ADN at the same time may occur. In this case, the power flow of ADN will change a lot when compared with the situation that a user is connected to only one node of ADN. Therefore, a maximum openable capacity optimization model of ADN considering multiple users access is proposed in this paper to deal with the situation that multiple users such as distributed generations and loads are connected to multiple nodes of ADN at the same time. The improved non-dominated sorting genetic algorithm (NSGA-II) is utilized to solve the proposed model, and case study based on IEEE 33-bus ADN is performed for verifying the effectiveness of the proposed maximum openable capacity optimization method.

Abstract Purpose The aim of this study was to explore the role of galectin‐3 in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer cells and the potential mechanism. Methods Kaplan–Meier (KM)‐plot and The Cancer Genome Atlas (TCGA) databases were used to study the role of galectin‐3 in the prognosis of HER2‐positive breast cancer. The effects of galectin‐3 on cell proliferation, migration, invasion, and colony formation ability in HER2‐positive breast cancer cells were examined. The relationship between galectin‐3 and important components in the HER2 pathways, including HER2, epidermal growth factor receptor (EGFR), protein kinase B (AKT), and phosphatase and tensin homolog (PTEN), was further studied. Lentivirus and CRISPR/Cas9 were used to construct stable cell lines. Cell counting kit‐8 (CCK‐8) and apoptosis assays were used to study the relationship between galectin‐3 and trastuzumab. The effect of galectin‐3 on cell stemness was studied by mammosphere formation assay. The effects of galectin‐3 on stemness biomarkers and the Notch1 pathway were examined. Tumorigenic models were used to evaluate the effects of galectin‐3 on tumorigenesis and the therapeutic effect of trastuzumab in vivo. Results HER2‐positive breast cancer patients with a high expression level of LGALS3 (the gene encoding galectin‐3) messenger RNA (mRNA) showed a poor prognosis. Galectin‐3 promoted cancer malignancy through phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway activation and upregulated stemness by activating the Notch1 signaling pathway in HER2‐positive breast cancer cells. These two factors contributed to the enhancement of trastuzumab resistance in cells. Knockout of LGALS3 had a synergistic therapeutic effect with trastuzumab both in vitro and in vivo. Conclusions Galectin‐3 may represent a prognostic predictor and therapeutic target for HER2‐positive breast cancer.

The serious problem of wind power curtailment in northern China has created a pressing need to enhance the peak-shaving ability of the power system. As the main source of power supply in northern China, combined heat and power (CHP) units have significant potential for peak-shaving. Currently, the Chinese government encourages CHP plants to increase their peak-shaving capacity by installing power-to-heat (P2H) equipment. In addition, the government has implemented auxiliary service market policies to encourage CHP plants to provide peak-shaving services. In order to maximize economic benefits for CHP plants, this paper proposes an optimal configuration method of P2H equipment with the static payback time (SPT) as the objective function. Cost and income models of installing the P2H equipment are constructed by taking into account the auxiliary service market policies. The peak-shaving income model of the CHP plant is derived emphatically as a key part of the proposed method. Finally, the district heating region in Jilin province is used as a case study example. The results show that adding the P2H equipment is significantly effective in improving the peak-shaving ability of CHP units, and investing in heat pumps is more cost-effective than electric boilers. The proposed method can be applied to other northern regions relying on CHP units for central heating, providing a valuable solution to the problem of wind power curtailment in these regions.

To solve the ghosting artifacts problem in dynamic scene multi-scale exposure fusion, an improved multi-exposure fusion method has been proposed without ghosting based on the exposure fusion framework and the color dissimilarity feature of this study. This fusion method can be further applied to power system monitoring and unmanned aerial vehicle monitoring. In this study, first, an improved exposure fusion framework based on the camera response model was applied to preprocess the input image sequence. Second, the initial weight map was estimated by multiplying four weight items. In removing the ghosting weight term, an improved color dissimilarity feature was used to detect the object motion features in dynamic scenes. Finally, the improved pyramid model as adopted to retain detailed information about the poor exposure areas. Experimental results indicated that the proposed method improves the performance of images in terms of sharpness, detail processing, and ghosting artifacts removal and is superior to the five existing multi-exposure image fusion (MEF) methods in quality evaluation.

Sensitive and accurate determination of aflatoxin B1 in food samples is urgently required for food safety, environment monitoring and human health due to its high toxicity. Here, we constructed an aptasensor with two fluorescent signals for determination of AFB1 in food samples by combining AIEgesns (TPE-Z) as fluorescent probe, the highly specific aptamer molecular label with Cy5 as the recognition element and GO as the fluorescence quencher. Upon the addition of AFB1, the fluorescence signal of the aptasensor platform turn from “off” to “on” with two fluorescent signals. The aptasensor provided a sensitivity (0.04 ng/mL), specificity and reliable approach for AFB1 detection. It had distinct advantage in detection sensitivity compared with single fluorescent signal aptasensor. Moreover, it was applied to analysis AFB1 in food samples (rice, corn and soybean) with satisfactory results.

Abstract Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples of primary tumors and axillary lymph nodes. We identified nine cancer cell subclusters including CD44 + / ALDH2 + /ALDH6A1 + breast cancer stem cells (BCSCs), which had a copy-number variants profile similar to that of normal breast tissue. Importantly, BCSCs existed only in primary tumors and evolved into metastatic clusters infiltrating into lymph nodes. Furthermore, transcriptome data suggested that NECTIN2-TIGIT-mediated interactions between metastatic breast cancer cells and tumor microenvironment (TME) cells, which promoted immune escape and lymph node metastasis. This study is the first to delineate the transcriptome profile of breast cancer lymph node metastasis using single-cell RNA sequencing. Our findings offer novel insights into the mechanisms underlying breast cancer metastasis and have implications in developing novel therapies to inhibit the initiation of breast cancer metastasis.

This study aims to investigate the prognostic impact of peripheral blood markers in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy. In the current multicenter study, 157 advanced NSCLC cases treated by immunotherapy at three institutions were included. Biochemical parameters in baseline peripheral blood were collected. The associations between biochemical parameters and prognosis were investigated by the Kaplan–Meier survival analyses and Cox regression, and the predictive performances of biomarkers were evaluated via receiver operating characteristic analysis. The neutrophil-to-lymphocyte ratio (NLR) (progression-free survival [PFS]: hazard ratio [HR], 1.766; 95% confidence interval [CI], 1.311–2.380; p < 0.001; overall survival [OS]: HR, 1.283; 95% CI, 1.120–1.469; p < 0.001) and red blood cell distribution width (RDW) (PFS: HR, 1.052; 95% CI, 1.005–1.102; p = 0.031; OS: HR, 1.044; 95% CI, 1.001–1.091; p = 0.042) were revealed as independent predictors for both PFS and OS. In addition, NLR ≥3.79 (1-year PFS, 24.2% [95% CI, 15.2%–38.4%] versus 27.3% [95% CI, 18.2%–41.1%], p = 0.041; 1-year OS, 44.2% [95% CI, 32.5%–60.1%] versus 71.8% [95% CI, 60.6%–85.2%], p < 0.001) or RDW ≥44.8 g/L (1-year PFS, 19.2% [95% CI, 11.4%–32.3%] versus 31.7% [95% CI, 21.9%–46.0%], p = 0.049; 1-year OS, 54.0% [95% CI, 42.7%–68.3%] versus 63.1% [95% CI, 50.6%–78.6%], p = 0.014) was significantly correlated to poorer PFS and OS than NLR < 3.79 or RDW

Abstract To determine the prognostic value of the timing of circulating breast tumour cell measurement during treatment, peripheral blood from 164 patients with breast disease was collected. Circulating tumour cells (CTCs) were enriched by using immunomagnetic nanospheres (IMNs) and were identified by using immunofluorescent staining. The CTC shows nuclear-positive, EpCAM-positive, CK19-positive, and CD45-negative. Patients with CTC positivity (> 19/7.5 mL blood) had shorter progression-free survival (PFS) and overall survival (OS) than those with negative results (≤ 19/7.5 mL blood) at baseline. Surgery caused an increase in the number and prevalence of CTCs, and the effect disappeared on day 14 after surgery. During adjuvant chemotherapy, CTCs detected before therapy was only correlated with PFS; however, CTCs at the end of adjuvant chemotherapy were correlated with both PFS and OS. The PFS and OS of the CTC-positive group were significantly shorter than those of the CTC-negative group at the end-point follow-up visit. The prognostic value of CTCs at different measurement time points was demonstrated during breast cancer treatment. Surgery and chemotherapy affected the prevalence of CTCs, leading to different prognostic relevance of CTCs at different treatment stages. CTCs detected at baseline or in the late phase of treatment are preferable for prognosis.

Megaprojects are characterized by significant environmental uncertainty and technical complexity, which bring great challenges to engineering construction. Cross-organizational collaborative innovation is an important way to solve these problems. As the main body that understands the difficulties of the construction site and uses innovative products, the participation of megaproject participants is not only conducive to increasing innovation efficiency but also conducive to the application and promotion of innovative achievements. The collaborative innovation behavior of the participants in megaprojects under the reward and punishment incentive mechanism was studied. A game model between different participants was built by combining evolutionary game theory with prospect theory. Then, the dynamic evolution process of the collaborative innovation strategy of participants was analyzed, and the main factors affecting the evolutionary stability strategy of collaborative innovation through numerical simulation were examined. The research results indicate that reward and punishment incentives of collaborative innovation can encourage participants to choose the evolutionary stability strategy of participating in collaborative innovation from both objective and subjective aspects. Factors, such as the cost of participating, the synergy coefficient, the proportion of collaborative revenue distribution, and risk preference, can influence participants’ willingness to engage in collaborative innovation to different degrees.

Normal power line insulators ensure the safe transmission of electricity. The defects of the insulator reduce the insulation, which may lead to the failure of power transmission systems. As unmanned aerial vehicles (UAVs) have developed rapidly, it is possible for workers to take and upload aerial images of insulators. Proposing a technology to detect insulator defects with high accuracy in a short time can be of great value. The existing methods suffer from complex backgrounds so that they have to locate and extract the insulators at first. Some of them make detection relative to some specific conditions such as angle, brightness, and object scale. This study aims to make end-to-end detections using aerial images of insulators, giving the locations of insulators and defects at the same time while overcoming the disadvantages mentioned above. A DEtection TRansformer (DETR) having an encoder–decoder architecture adopts convolutional neural network (CNN) as the backbone network, applies a self-attention mechanism for computing, and utilizes object queries instead of a hand-crafted process to give the direct predictions. We modified this for insulator detection in complex aerial images. Based on the dataset we constructed, our model can get 97.97 in mean average precision when setting the threshold of intersection over union at 0.5, which is better than Cascade R-CNN and YOLOv5. The inference speed of our model can reach 25 frames per second, which is qualified for actual use. Experimental results demonstrate that our model meets the robustness and accuracy requirements for insulator defect detection.

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that often occurs in the elderly. Electroencephalography (EEG) signals have a strong correlation with neuropsychological test results and brain structural changes. It has become an effective aid in the early diagnosis of AD by exploiting abnormal brain activity. Because the original EEG has the characteristics of weak amplitude, strong background noise and randomness, the research on intelligent AD recognition based on machine learning is still in the exploratory stage. This paper proposes the discriminant subspace low-rank representation (DSLRR) algorithm for EEG-based AD and mild cognitive impairment (MCI) recognition. The subspace learning and low-rank representation are flexibly integrated into a feature representation model. On the one hand, based on the low-rank representation, the graph discriminant embedding is introduced to constrain the representation coefficients, so that the robust representation coefficients can preserve the local manifold structure of the EEG data. On the other hand, the least squares regression, principle component analysis, and global graph embedding are introduced into the subspace learning, to make the model more discriminative. The objective function of DSLRR is solved by the inexact augmented Lagrange multiplier method. The experimental results show that the DSLRR algorithm has good classification performance, which is helpful for in-depth research on AD and MCI recognition.

Urban agglomeration has become the main form of regional spatial organization in China. While most of the existing studies of urban agglomeration in China have focused on the eastern coastal areas, urban agglomeration with mid-level development in the rest of the country has been overlooked. To better understand the urbanization process of the mid-level developing urban agglomeration, this study investigated the clustering pattern and the drivers of both urban population and firm dynamics during 2005–2015 in the Changsha-Zhuzhou-Xiangtan (Chang-Zhu-Tan) urban agglomeration of China using the methods of kernel density estimation and geographic detection. Our results show that centralization was obvious, although decentralization also occurred in Chang-Zhu-Tan, and that the spatial agglomeration was promoted by several factors, such as administrative resources, location advantage, labor cost, and consumption capacity. Some problems hindering the development of this region were also discovered: administrative resources played a critical role in urbanization because small towns and villages did not receive enough attention, and the effect of local policy was not as beneficial as expected. These findings partly explain the relatively slow development of mid-level developing urban agglomerations and have important implications for promoting healthier urbanization.

Colocation mining is useful for understanding the interactions or dependencies that occur among geographic phenomena. Most colocation mining methods are based on planar space. However, in urban spaces, many human-related activities are constrained by a road network. Planar colocation mining methods are not suitable for studying the concerning geographic phenomena in an urban space. In this paper, we propose a visualization method to discover colocation patterns constrained by a road network. The method consists of two major components: network kernel density estimation and network colocation rule map construction. In the colocation rule map construction component, spatial interactions among spatial network geographic phenomena are modeled based on the idea of color mixing. We use simulated datasets with different spatial patterns, different sample sizes, and different maximum distances between road network events to test our method. The results show that our method is effective for mining colocation patterns in different situations. We also change the resolution of the network colocation rule maps, and the results show that the resolution has little influence on the results. In the case study, we apply our method to explore the spatial association between crimes and city facilities in the Loop and the Near North Side districts of Chicago.

Due to the input power and output power do not match in real time, single-stage power factor correction converters have large double-line-frequency ripple at the output voltage. The double-line-frequency ripple voltage will cause some electronic devices to work abnormally, and limit the control loop bandwidth of power factor correction converter. In order to reduce the output double-line-frequency ripple voltage, a single-stage Flyback power factor correction converter with Buck ripple suppressor is used in this paper, the Buck ripple suppressor can generate same magnitude but 180° phase shifted voltage as Flyback power factor correction converter output voltage ripple. Adaptive on-time control is adopted in the Buck ripple suppressor benefiting with its wider bandwidth and fast dynamic response. The switching frequency range and stability of Buck ripple suppressor under constant on-time control and adaptive on-time control are discussed. By establishing the input-output audio susceptibility model, the output double-line-frequency ripple suppression performance is analyzed. Buck ripple suppressor using adaptive on-time control can suppress double-line-frequency ripple voltage effectively with the fast dynamic response and high efficiency. Simulation and experimental results are given to verify the theoretical analysis.

Magnetic resonance imaging (MRI) can have a good diagnostic function for important organs and parts of the body. MRI technology has become a common and important disease detection technology. At the same time, medical imaging data is increasing at an explosive rate. Retrieving similar medical images from a huge database is of great significance to doctors’ auxiliary diagnosis and treatment. In this paper, combining the advantages of sparse representation and metric learning, a sparse representation-based discriminative metric learning (SRDML) approach is proposed for medical image retrieval of brain MRI. The SRDML approach uses a sparse representation framework to learn robust feature representation of brain MRI, and uses metric learning to project new features into the metric space with matching discrimination. In such a metric space, the optimal similarity measure is obtained by using the local constraints of atoms and the pairwise constraints of coding coefficients, so that the distance between similar images is less than the given threshold, and the distance between dissimilar images is greater than another given threshold. The experiments are designed and tested on the brain MRI dataset created by Chang. Experimental results show that the SRDML approach can obtain satisfactory retrieval performance and achieve accurate brain MRI image retrieval.

Aucuba (Garryaceae), which includes approximately ten evergreen woody species, is a genus endemic to East Asia. Their striking morphological features give Aucuba species remarkable ornamental value. Owing to high levels of morphological divergence and plasticity, species definitions of Aucuba remain perplexing and problematic. Here, we sequenced and characterized the complete plastid genomes (plastomes) of three Aucuba species: Aucuba chlorascens, Aucuba eriobotryifolia, and Aucuba japonica. Incorporating Aucuba plastomes available in GenBank, a total of seven Aucuba plastomes, representing six out of ten species of Aucuba, were used for comparative plastome analysis, phylogenetic analysis and divergence time estimation in this study. Comparative analyses revealed that plastomes of Aucuba are highly conserved in size, structure, gene content, and organization, and exhibit high levels of sequence similarity. Phylogenetic reconstruction based on 68 plastid protein-coding genes strongly supported the monophyly of Garryales, Garryaceae and Aucuba. Aucuba eriobotryifolia was sister to the other Aucuba species examined, consistent with its unique fused anther locule. The divergence time of Aucuba was estimated to be approximately late Miocene. Extant Aucuba species derived from recent divergence events associated with the establishment of monsoonal climates in East Asia and climatic fluctuations.

The leading cause of many respiratory diseases is an ongoing and progressive inflammatory response. Traditionally, inflammatory lung diseases were studied primarily through animal models, cell cultures, and organoids. These technologies have certain limitations, despite their great contributions to the study of respiratory diseases. Precision-cut lung slices (PCLS) are thin, uniform tissue slices made from human or animal lung tissue and are widely used extensively both nationally and internationally as an in vitro organotypic model. Human lung slices bridge the gap between in vivo and in vitro models, and they can replicate the living lung environment well while preserving the lungs’ basic structures, such as their primitive cells and trachea. However, there is no perfect model that can completely replace the structure of the human lung, and there is still a long way to go in the research of lung slice technology. This review details and analyzes the strengths and weaknesses of precision lung slices as an in vitro model for exploring respiratory diseases associated with inflammation, as well as recent advances in this field.

Localization of the underwater magnetic sensor arrays plays a pivotal role in the magnetic silencing facility. A localization approach is proposed for underwater sensors based on the optimization of magnetic field gradients in the inverse problem of localization. In the localization system, a solenoid coil carrying direct current serves as the magnetic source. By measuring the magnetic field generated by the magnetic source in different positions, an objective function is established. The position vector of the sensor is determined by a novel multi-swarm particle swarm optimization with dynamic learning strategy. Without the optimization of the magnetic source’s positions, the sensors’ positions, especially in the z-axis direction, struggle to meet the requested localization. A strategy is proposed to optimize the positions of the magnetic source based on magnetic field gradients in the three directions of x, y and z axes. Compared with the former method, the model experiments show that the proposed method could achieve a 10 cm location error for the position type 2 sensor and meet the request of localization.

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in patients with chronic kidney disease (CKD). miRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only resulted in LVH but also suppressed miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuated LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes led to cardiomyocyte hypertrophy by upregulating the calcineurin signaling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23, uremic toxin, angiotensin II, and transforming growth factor–β, suppressed cardiac miRNA-30 expression, while miRNA-30 supplementation blunted cardiomyocyte hypertrophy induced by such factors. These results uncover a potentially novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.

Heavy metals and As (HMs) pollution in mining areas are a widespread environmental concern. In this study, ground water, surface water, and sediment samples around the Dexing area, one of the largest Cu-polymetallic ore clusters in China, were collected to examine the concentrations and distributions of As, Cd, Cr, Cu, Hg, Pb, and Zn. Pollution indices, geo-accumulation index, and potential ecological risk index were used to estimate the pollution characteristics and ecological risk of HMs. The results show that the major pollutants in the surface water were Cd, Cu, Zn, and Pb, while the dominant ecological risk of HMs in the sediments originated from Cu, As, Hg, and Cd. Moreover, HMs in the surface water and sediments exhibited substantial spatial heterogeneity in the study area, indicating a severely disturbed environment due to mining activities. The proportions of HM pollutions were higher in the Dexing River and its tributaries than in the Le’an River and its tributaries. The surface water pollution was predominant at the tributaries closest to the mine area, while the sediment contamination has been expanded several kilometers downstream of the major rivers. Overall, the ecological risk of HMs was higher in the sediments than in the surface water.

Growing concerns about urban runoff pollution and water scarcity caused by urbanization have prompted the application of bioretention facilities to manage urban stormwater. The purpose of this study was to evaluate the performance of proposed bioretention facilities regarding road runoff pollutant removal and the variation characteristics of the media physicochemical properties and microbial diversity in dry-cold regions. Two types of bioretention facilities were designed and then constructed in Tianjin Eco-city, China, on the basis of combined soil filter media screened by a laboratory-scale test with a modified bioretention facility (MBF) containing soil moisture conservation ropes. Redundancy analysis was performed to evaluate the relationships between the variation in media physicochemical properties and microbial communities. An increase in media moisture could promote an increase in the relative abundance of several dominant microbial communities. In the MBF, the relatively low nitrate-nitrogen (NO3-N) (0.75 mg/L) and total nitrogen (TN) (4.71 mg/L) effluent concentrations, as well as better removal efficiencies for TN and NO3-N in challenge tests, were mainly attributed to the greater relative abundance of Proteobacteria (25.2%) that are involved in the microbial nitrogen transformation process. The MBF also had greater media microbial richness (5253 operational taxonomic units) compared to the conventional bioretention facility and in situ saline soils. The results indicate that stormwater runoff treated by both bioretention facilities has potential use for daily greening and road spraying. The proposed design approach for bioretention facilities is applicable to LID practices and sustainable stormwater management in other urban regions.

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that poses a clinical challenge. Thus, new therapy strategies are urgently needed. The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors. Here, we first demonstrate that inhibition of ATR by selective inhibitor AZD6738 can enhance AZD1775-caused growth inhibition in TNBC. Our results show that the enhanced cell death is attributed to repressed DNA damage repair and excessive replication stress, thereby causing increased DNA damage reflected by accumulation of the DNA double-strand-break marker γH2AX. On the other hand, combined treatment with AZD6738 and AZD1775 forces mitotic entry of cells with DNA damages by activating CDK1 activity, inducing severely aberrant mitosis and mitotic catastrophe, ultimately resulting in cell death. Dual inhibition of WEE1 and ATR also inactivated RAD51-mediated homologous recombination, which sensitized TNBC cells to cisplatin and PARP inhibitor. Here, based on the preclinical results that ATR inhibition synergizes with WEE1 inhibition in TNBC, we propose that this combination therapy alone, or in parallel with chemotherapy, represents an innovative and potent targeted therapy in TNBC.

For pulse train (PT) controlled switching converter, when it operates in continuous conduction mode (CCM) and discontinuous conduction mode (DCM), there exist disadvantages of low frequency oscillation and narrow load range, respectively. To avoid these disadvantages of PT controlled switching converter in CCM and DCM, a PT controlled boost converter operating in pseudo continuous conduction mode (PCCM) is taken as the research object in this paper, its working principle has been analyzed in detail. Based on the analysis of output voltage ripple during one switching cycle, the combination of high- and low-power control pulses in a repetition cycle is analyzed and the expression of output voltage ripple is derived for different load conditions. Finally, simulation and experiment are performed to verify the correctness of the control pulse combinations and the output voltage ripple analysis. Results show that compared with DCM and CCM boost converters, the PT controlled PCCM boost converter not only has wider load range, but also can suppress low frequency oscillation.

Grain shape of rice is an important trait for both yield and quality. A rice rk4 (round kernel) mutant was obtained from the japonica variety Zhonghua 11 by radiation of 60Co-γ. The grain width of the mutant was increased and the length was decreased. Simultaneously, the 1000-grain weight was slightly reduced, therefore the grain shape of the mutant tended to be small and round. In this study, genetic analysis and gene mapping of the mutant gene were carried out using the F2 and F3 populations derived from the mutant and the indica variety Xianhui 8006. The results suggested that the round kernel was controlled by a single recessive allele (rk4) which was located on chromosome 5. The RK4 gene was further mapped between the molecular markers LSTS5-77 and LSTS5-60 with 0.57 and 0.096 cM, respectively. A BAC clone was found to span the RK4 locus, and the RK4 gene was placed in a 46 kb region that contains six annotated genes according to the available sequence annotation database. This result will help us to isolate the RK4 gene and reveal the molecular mechanism of the round kernel in rice.

The complete plastome of Rhoiptelea chiliantha was sequenced and assembled in this study. The circular plastome of R. chiliantha is 161,702 bp in size, which contains a large single-copy region (LSC, 90,447 bp), a short single-copy region (SSC, 19,081 bp) and two inverted repeat sequences (IRs, 26,087 bp, each). It is totally comprised of 133 genes, including 88 protein-coding genes, eight ribosomal RNA, and 37 transfer RNA. The phylogenetic analysis shows that R. chiliantha is sister to the clade including remaining Juglandaceae species.

Aflatoxin B1 (AFB1) is one of the most frequently-found mycotoxins in contaminated food. As the content of mycotoxins is particularly low in food, the development of probes to detect AFB1 in foods with high sensitivity and selectivity is an urgent social need for the evaluation of food quality. Numerous techniques have been developed to monitor AFB1. Nevertheless, most of them require cumbersome, labor-consuming, and sophisticated instruments, which have limited their application. An aptamer is a single, short nucleic acid sequence that is capable of recognizing different targets. Owing to their unique properties, aptamers have been considered as alternatives to antibodies. Aptasensors are considered to be an emerging strategy for the quantification of aflatoxin B1 with high selectivity and sensitivity. In this review, we summarize recent developments in colormetric, electrochemical, SERS, and fluorescent aptasensors for the quantification of AFB1. Finally, the perspectives and current challenges of aptasensors for AFB1 are outlined.

Gold nanoparticles (AuNPs) made from self-assembling peptides have been used in many research fields and attracted a great deal of attention due to their high stability, biocompatibility and functionality. However, existing preparation methods for peptide-coated AuNPs are post-synthesis processes, which are complicated and time consuming. Therefore, a one-step preparation method for peptide-coated AuNPs is proposed here. The AuNPs obtained by this method exhibit good stability. Importantly, peptide-coated AuNPs with precise different sizes can be prepared by this method through pH control of reducing reagent tyrosine in range of 10.0~12.7. Thus, the one-step preparation method proposed here provides a significant tool for the research in different fields concerning NP size, stability and biocompatibility.

Long-term growth of genetically modified plants (GMPs) has raised concerns regarding their ecological effects. Here, FLX-pyrosequencing of region I (18S) and region II (ITS1, 5.8S and ITS2) rDNA was used to characterize fungal communities in soil samples after 10-year monoculture of one representative transgenic cotton line (TC-10) and 15-year plantation of various transgenic cotton cultivars (TC-15mix) over four seasons. Soil fungal communities in the rhizosphere of non-transgenic control (CC) were also compared. No notable differences were observed in soil fertility variables among CC, TC-10 and TC-15mix. Within seasons, the different estimations were statistically indistinguishable. There were 411 and 2 067 fungal operational taxonomic units in the two regions, respectively. More than 75% of fungal taxa were stable in both CC and TC except for individual taxa with significantly different abundance between TC and CC. Statistical analysis revealed no significant differences between CC and TC-10, while discrimination of separating TC-15mix from CC and TC-10 with 37.86% explained variance in PCoA and a significant difference of Shannon indexes between TC-10 and TC-15mix were observed in region II. As TC-15mix planted with a mixture of transgenic cottons (Zhongmian-29, 30, and 33B) for over 5 years, different genetic modifications may introduce variations in fungal diversity. Further clarification is necessary by detecting the fungal dynamic changes in sites planted in monoculture of various transgenic cottons. Overall, we conclude that monoculture of one representative transgenic cotton cultivar may have no effect on fungal diversity compared with conventional cotton. Furthermore, the choice of amplified region and methodology has potential to affect the outcome of the comparison between GM-crop and its parental line.

To simultaneously analyze mutations and expression levels of multiple genes on one detection platform, we proposed a method termed "multiplex ligation-dependent probe amplification-digital amplification coupled with hydrogel bead-array" (MLPA-DABA) and applied it to diagnose colorectal cancer (CRC). CRC cells and tissues were sampled to extract nucleic acid, perform MLPA with sequence-tagged probes, perform digital emulsion polymerase chain reaction (PCR), and produce a hydrogel bead-array to immobilize beads and form a single bead layer on the array. After hybridization with fluorescent probes, the number of colored beads, which reflects the abundance of expressed genes and the mutation rate, was counted for diagnosis. Only red or green beads occurred on the chips in the mixed samples, indicating the success of single-molecule PCR. When a one-source sample was analyzed using mixed MLPA probes, beads of only one color occurred, suggesting the high specificity of the method in analyzing CRC mutation and gene expression. In gene expression analysis of a CRC tissue from one CRC patient, the mutant percentage was 3.1%, and the expression levels of CRC-related genes were much higher than those of normal tissue. The highly sensitive MLPA-DABA succeeds in the relative quantification of mutations and gene expressions of exfoliated cells in stool samples of CRC patients on the same chip platform. MLPA-DABA coupled with hydrogel bead-array is a promising method in the non-invasive diagnosis of CRC.