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Abstract To aid in the diagnosis, monitoring, and surveillance of bladder carcinoma, this study aimed to develop and test an algorithm that creates a referenceable bladder map rendered from standard cystoscopy videos without the need for specialized equipment. A vision-based algorithm was developed to generate 2D bladder maps from individual video frames, by sequentially stitching image frames based on matching surface features, and subsequently localize and track frames during reevaluation. The algorithm was developed and calibrated in a 2D model and 3D anthropomorphic bladder phantom. The performance was evaluated in vivo in swine and with retrospective clinical cystoscopy video. Results showed that the algorithm was capable of capturing and stitching intravesical images with different sweeping patterns. Between 93% and 99% of frames had sufficient features for bladder map generation. Upon reevaluation, the cystoscope accurately localized a frame within 4.5 s. In swine, a virtual mucosal surface map was generated that matched the explant anatomy. A surface map could be generated based on archived patient cystoscopy images. This tool could aid recording and referencing pathologic findings and biopsy or treatment locations for subsequent procedures and may have utility in patients with metachronous bladder cancer and in low-resource settings.

Abstract Tamoxifen (TAM) resistance is a major challenge in treating oestrogen receptor-positive (ER+) breast cancers. It is possible that the H2S synthase cystathionine-γ-lyase (CSE), which has been previously shown to promote tumour growth and metastasis in other cancer cells, is involved in this resistance. Therefore, we investigated CSE's role and potential mechanisms in TAM-resistant breast cancer cells. First, we examined the effect of CSE expression on TAM sensitivity and resistance in MCF7 (breast cancer) cells. The findings revealed that CSE was directly associated with TAM sensitivity and involved in TAM resistance in ER+ breast cancer cells, indicating that it may be useful as a biomarker. Next, we wanted to determine the molecular mechanism of CSE's role in TAM resistance. Using cell migration, co-immunoprecipitation, western blotting, and cell viability assays, we determined that the CSE/H2S system can affect the expression of PPARγ by promoting the sulfhydrylation of PPARγ, which regulates the transcriptional activity of ACSL1. ACSL1, in turn, influences STAT3 activation by affecting the phosphorylation, palmitoylation and dimerization of STAT3, ultimately leading to the development of TAM resistance in breast cancer. Finally, we examined the effect of CSE inhibitors on reducing drug resistance to determine whether CSE may be used as a biomarker of TAM resistance. We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.

Abstract The construction of large reservoirs has modified the process of water and sediment transport downstream, resulting in changes in the morphology of the river cross-section. Changes in water and sand transport and cross-sectional morphology are reflected in the rating curve at the cross-section. This study analyzed the variations in the rating curve at the Huayuankou (HYK) section and their influencing factors, and conducted water level predictions based on this relationship. The findings revealed that while the annual mean water level has shown a declining tendency over the past 20 years, the annual mean discharge has shown a constant pattern. The rating curve at this stretch narrowed from a rope-loop type curve in its natural condition to a more stable single curve as a result of the construction of the dam upstream of the HYK section. The effect of pre-flood section morphology and the water–sediment process on the scattering degree of the rating curve is inverse; increasing roughness and hydraulic radius decreases scattering degree, while increasing sand content and sand transport rate increases scattering degree. Using the measured data from 2020 as an example, the feasibility of predicting cross-sectional water levels using the rating curve was verified. The prediction results were accurate when the flow was between 1000 and 2800 m3/s; However, when the flow was between 2800 and 4000 m3/s, the forecast results were typically slightly lower than the measured values. Overall, the method demonstrates good predictive accuracy. Insight from the method can be used to predict water levels to better inform decision making about water resources management, and flood emergency response in the lower Yellow River.

Abstract Ultra-precision machining requires system modelling that both satisfies explainability and conforms to data fidelity. Existing modelling approaches, whether based on data-driven methods in present artificial intelligence (AI) or on first-principle knowledge, fall short of these qualities in high-demanding industrial applications. Therefore, this paper develops an explainable and generalizable ‘grey-box’ AI informatics method for real-world dynamic system modelling. Such a grey-box model serves as a multiscale ‘world model’ by integrating the first principles of the system in a white-box architecture with data-fitting black boxes for varying hyperparameters of the white box. The physical principles serve as an explainable global meta-structure of the real-world system driven by physical knowledge, while the black boxes enhance local fitting accuracy driven by training data. The grey-box model thus encapsulates implicit variables and relationships that a standalone white-box model or black-box model fails to capture. Case study on an industrial cleanroom high-precision temperature regulation system verifies that the grey-box method outperforms existing modelling methods and is suitable for varying operating conditions.

Abstract For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of − 65 dB at 1.55 μm, with an operating bandwidth spanning 100 nm (1.5–1.6 μm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 μm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

Abstract Flood forecasting using traditional physical hydrology models requires consideration of multiple complex physical processes including the spatio-temporal distribution of rainfall, the spatial heterogeneity of watershed sub-surface characteristics, and runoff generation and routing behaviours. Data-driven models offer novel solutions to these challenges, though they are hindered by difficulties in hyperparameter selection and a decline in prediction stability as the lead time extends. This study introduces a hybrid model, the RS-LSTM-Transformer, which combines Random Search (RS), Long Short-Term Memory networks (LSTM), and the Transformer architecture. Applied to the typical Jingle watershed in the middle reaches of the Yellow River, this model utilises rainfall and runoff data from basin sites to simulate flood processes, and its outcomes are compared against those from RS-LSTM, RS-Transformer, RS-BP, and RS-MLP models. It was evaluated against RS-LSTM, RS-Transformer, RS-BP, and RS-MLP models using the Nash–Sutcliffe Efficiency Coefficient (NSE), Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Bias percentage as metrics. At a 1-h lead time during calibration and validation, the RS-LSTM-Transformer model achieved NSE, RMSE, MAE, and Bias values of 0.970, 14.001m3/s, 5.304m3/s, 0.501% and 0.953, 14.124m3/s, 6.365m3/s, 0.523%, respectively. These results demonstrate the model's superior simulation capabilities and robustness, providing more accurate peak flow forecasts as the lead time increases. The study highlights the RS-LSTM-Transformer model's potential in flood forecasting and the advantages of integrating various data-driven approaches for innovative modelling.

Abstract Osteoporosis is usually caused by excessive bone resorption and energy metabolism plays a critical role in the development of osteoporosis. However, little is known about the role of energy metabolism-related genes in osteoporosis. This study aimed to explore the important energy metabolism-related genes involved in the development of osteoporosis and develop a diagnosis signature for osteoporosis. The GSE56814, GSE62402, and GSE7158 datasets were downloaded from the NCBI Gene Expression Omnibus. The intersection of differentially expressed genes between high and low levels of body mineral density (BMD) and genes related to energy metabolism were screened as differentially expressed energy metabolism genes (DE-EMGs). Subsequently, a DE-EMG-based diagnostic model was constructed and differential expression of genes in the model was validated by RT-qPCR. Furthermore, a receiver operating characteristic curve and nomogram model were constructed to evaluate the predictive ability of the diagnostic model. Finally, the immune cell types in the merged samples and networks associated with the selected optimal DE-EMGs were constructed. A total of 72 overlapped genes were selected as DE-EMGs, and a five DE-EMG based diagnostic model consisting B4GALT4, ADH4, ACAD11, B4GALT2, and PPP1R3C was established. The areas under the curve of the five genes in the merged training dataset and B4GALT2 in the validation dataset were 0.784 and 0.790, respectively. Moreover, good prognostic prediction ability was observed using the nomogram model (C index = 0.9201; P = 5.507e−14). Significant differences were observed in five immune cell types between the high- and low-BMD groups. These included central memory, effector memory, and activated CD8 T cells, as well as regulatory T cells and activated B cells. A network related to DE-EMGs was constructed, including hsa-miR-23b-3p, DANCR, 17 small-molecule drugs, and two Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways and pyruvate metabolism. Our findings highlighted the important roles of DE-EMGs in the development of osteoporosis. Furthermore, the DANCR/hsa-miR-23b-3p/B4GALT4 axis might provide novel molecular insights into the process of osteoporosis development.

Abstract Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, β-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research.

Abstract Asbestos is widely used in construction, manufacturing, and other common industrial fields. Human activities such as mining, processing, and transportation can release heavy metals from asbestos into the surrounding soil environment, posing a health hazard to the mining area's environment and its surrounding residents. The purpose of the present study was to determine the extent of ecological and human health damage caused by asbestos pollution, as well as the primary contributors to the contamination, by examining a large asbestos mine and the surrounding soil in China. The level of heavy metal pollution in soil and sources were analyzed using methods such as the geo-accumulation index (Igeo), potential ecological risk index (RI), and positive matrix factorization (PMF) model. A Monte Carlo simulation-based health risk model was employed to assess the health risks of heavy metals in the study area’s soil to human beings. The results showed that the concentrations of As, Pb, Cr, Cu, and Ni in the soil were 1.74, 0.13, 13.31, 0.33, and 33.37 times higher than the local soil background values, respectively. The Igeo assessment indicated significant accumulation effects for Ni, Cr, and As. The RI evaluation revealed extremely high comprehensive ecological risks (RI ≥ 444) in the vicinity of the waste residue heap and beneficiation area, with Ni exhibiting strong individual potential ecological risk (Eir ≥ 320). The soil health risk assessment demonstrated that As and Cr posed carcinogenic risks to adults, with mean carcinogenic indices (CR) of 1.56E − 05 and 4.14E − 06, respectively. As, Cr, and Cd posed carcinogenic risks to children, with mean CRs of 1.08E − 04, 1.61E − 05, and 2.68E − 06, respectively. Cr also posed certain non-carcinogenic risks to both adults and children. The PMF model identified asbestos contamination as the primary source of heavy metals in the soil surrounding the asbestos mining area, contributing to 79.0%. According to this study, it is recommended that management exercise oversight and regulation over the concentrations of Ni, Cr, Cd, and As in the soil adjacent to asbestos mines, establish a designated control zone to restrict population activities, and locate residential zones at a safe distance from the asbestos mine production zone.

Abstract Medin is a common vascular amyloidogenic peptide recently implicated in Alzheimer’s disease (AD) and vascular dementia and its pathology remains unknown. We aim to identify changes in transcriptomic profiles and pathways in human brain microvascular endothelial cells (HBMVECs) exposed to medin, compare that to exposure to β-amyloid (Aβ) and evaluate protection by monosialoganglioside-containing nanoliposomes (NL). HBMVECs were exposed for 20 h to medin (5 µM) without or with Aβ(1-42) (2 µM) or NL (300 µg/mL), and RNA-seq with signaling pathway analyses were performed. Separately, reverse transcription polymerase chain reaction of select identified genes was done in HBMVECs treated with medin (5 µM) without or with NFκB inhibitor RO106-9920 (10 µM) or NL (300 µg/mL). Medin caused upregulation of pro-inflammatory genes that was not aggravated by Aβ42 co-treatment but reversed by NL. Pathway analysis on differentially expressed genes revealed multiple pro-inflammatory signaling pathways, such as the tumor necrosis factor (TNF) and the nuclear factor-κB (NFkB) signaling pathways, were affected specifically by medin treatment. RO106-9920 and NL reduced medin-induced pro-inflammatory activation. Medin induced endothelial cell pro-inflammatory signaling in part via NFκB that was reversed by NL. This could have potential implications in the pathogenesis and treatment of vascular aging, AD and vascular dementia.

Abstract Insulin resistance (IR) is associated with a variety of cardiovascular diseases, but there are few studies on the correlation between IR and calcified aortic stenosis (CAS). In this study, the triglyceride-glucose (TyG) index, which reflects IR, was used to investigate the correlation between IR and CAS. The study included 183 elderly patients who were diagnosed with CAS by transthoracic echocardiography. The patients were matched 1:1 according to age and sex, and elderly patients who were hospitalized during the same period and underwent transthoracic echocardiography without aortic stenosis were included as the control group. The relationship between the TyG index and CAS was analyzed by a multivariable logistic regression model, curve fitting and trend test. Multivariate logistic regression analysis showed that the TyG index as a continuous variable was negatively associated with CAS (P

Abstract For Schatzker type II split-depressed tibial plateau fractures involving the fractures of anterolateral and posterolateral columns (APC), the optimal fixation scheme is controversial. The objectives of this study were: (1) to introduce a newly designed plate for treating APC fractures via biomechanical tests and finite element analysis (FEA), and (2) to compare it with two conventional fixation methods. APC fracture models were created and randomly assigned to three groups (Groups A-C). Group A was fixed with a 3.5-mm lateral locking plate, Group B was fixed with a 3.5-mm lateral locking plate and two 3.5-mm cannulated screws (hybrid fixation). Group C was fixed with the newly designed plate. It is an arched locking plate for fixing the lateral tibial plateau via the anterolateral supra-fibular-head approach. Each fracture model experienced a gradually increasing axial compressive load ranging from 250 to 750 N using a customized indenter. Biomechanical analysis demonstrated that the newly designed plate showed the minimum displacement among the three methods, followed by the hybrid fixation method. Conversely, the 3.5-mm lateral locking plate displayed the maximum displacement in APC fractures (p

Abstract Object detection has been widely applied in various fields with the rapid development of deep learning in recent years. However, detecting small objects is still a challenging task because of the limited information in features and the complex background. To further enhance the detection accuracy of small objects, this paper proposes an efficient single-shot detector with weight-based feature fusion (WFFA-SSD). First, a weight-based feature fusion block is designed to adaptively fuse information from several multi-scale feature maps. The feature fusion block can exploit contextual information for feature maps with large resolutions. Then, a context attention block is applied to reinforce the local region in the feature maps. Moreover, a pyramids aggregation block is applied to combine the two feature pyramids to classify and locate target objects. The experimental results demonstrate that the proposed WFFA-SSD achieves higher mean Average Precision (mAP) under the premise of ensuring real-time performance. WFFA-SSD increases the mAP of the car by 4.12% on the test set of the CARPK.

Abstract The incorporation of energy conservation measures into production efficiency is widely recognized as a crucial aspect of contemporary industry. This study aims to develop interpretable and high-quality dispatching rules for energy-aware dynamic job shop scheduling (EDJSS). In comparison to the traditional modeling methods, this paper proposes a novel genetic programming with online feature selection mechanism to learn dispatching rules automatically. The idea of the novel GP method is to achieve a progressive transition from exploration to exploitation by relating the level of population diversity to the stopping criteria and elapsed duration. We hypothesize that diverse and promising individuals obtained from the novel GP method can guide the feature selection to design competitive rules. The proposed approach is compared with three GP-based algorithms and 20 benchmark rules in the different job shop conditions and scheduling objectives considered energy consumption. Experiments show that the proposed approach greatly outperforms the compared methods in generating more interpretable and effective rules. Overall, the average improvement over the best-evolved rules by the other three GP-based algorithms is 12.67%, 15.38%, and 11.59% in the meakspan with energy consumption (EMS), mean weighted tardiness with energy consumption (EMWT), and mean flow time with energy consumption (EMFT) scenarios, respectively.

Abstract This retrospective study compared proximal bone transport and distal bone transport in a series of cases diagnosed with large segmental tibial defects. Patients with a tibial segmental defect (> 5 cm) were eligible for inclusion. Twenty-nine patients were treated using proximal bone transport technique (PBT group) and 21 cases were managed by distal bone transport technique (DBT group). We recorded the demographic information, operation indexes, external fixation index (EFI), visual analog score (VAS), limb function scores, and complications. Patients were followed for 24–52 months. There was no significant difference in operation time, blood loss, time in frame, EFI and HSS score between the two groups (p > 0.05). However, the PBT group displayed better clinical effects than the DBT group, including higher AOFAS scores, lower VAS, and complication incidence (p

Abstract The considerable role of circular RNAs (circRNAs) make them prospective biomarkers in cancer therapy. Our study aimed to unveil the function of circ_0128846 in pancreatic cancer (PC). The expressions of circ_0128846, miR-1270 and NR3C1 mRNA were measured via RT-qPCR. The expressions of NR3C1 protein and apoptosis-related markers (Bax and Bcl-2) were measured via western blotting. CCK-8, colony-forming, or wound healing assay was respectively utilized to identify cell proliferation, growth and migration. Xenograft model was developed to evaluate tumor growth affected by circ_0128846 in vivo. The putative binding between miR-1270 and circ_0128846 or NR3C1 was testified by dual-luciferase reporter, RIP or pull-down assay. Circ_0128846 showed elevated expression in PC. Circ_0128846 deficiency restrained cancer cell proliferation, colony formation and migratory ability, enhanced cell apoptotic rate, and also impeded tumor development in vivo. Circ_0128846 directly targeted miR-1270 whose expression was declined in PC. The suppressive effects of silencing circ_0128846 on PC cell malignant phenotypes were largely reversed by miR-1270 inhibition. NR3C1 was targeted by miR-1270 and was highly regulated in PC. The repressive effects of NR3C1 knockdown on PC cell malignant phenotypes were partly abolished by miR-1270 inhibition. Circ_0128846 deficiency blocked PC progression via mediating the miR-1270/NR3C1 pathway, which partly illustrated PC pathogenesis.

Abstract The purpose of this study was to investigate the association between time restricted feeding (TRF) and different areas of cognitive function in the elderly in Chinese communities. This study consisted of 1353 community-dwelling Chinese older adults aged 60 years and older in Chongming area, Shanghai (563 males; the mean age, 73.38 ± 6.16 years). Mild cognitive impairment (MCI) and six different cognitive domains was assessed by the Chinese-version of Mini Mental State Examination (MMSE). Recording the eating time of each meal through oral inquiry to calculate the time window between the first meal and the last meal of the average day. Participants with an eating time window duration of more than 10 h were then identified, as well as those with eating time restricted to less than 10 h (TRF). Our study found that TRF may be associated with a higher incidence rate of cognitive impairment. TRF only limited the eating time window and did not change the frequency of participants' dietary intake. We used a linear regression model to study the association of TRF with cognitive function. After adjusting for confounding variables, the results showed that TRF was related to MMSE score (P

Abstract In the present study, we presented our experience with a new modified technique of shortening and re-lengthening using a monolateral external frame combined with a calcaneal intramedullary nail and compared it with the bone transport technique for the treatment of distal tibial periarticular post-traumatic defects. Forty-one patients were retrospectively analyzed. Among them 19 were treated using our modified shortening and re-lengthening technique (MSR group) and 22 by bone transport (BT group). The difference in external fixation time (EFT), external fixation index (EFI), self-rating anxiety scale (SAS), and complications were compared between the two groups. The mean EFT was 3.4 ± 0.6 months in the MSR group and 7.5 ± 1.4 months in the BT group; the EFI was 0.57 ± 0.06 month/cm and 1.32 ± 0.23 month/cm, respectively. The EFT, EFI, and SAS scores were significantly lower in the MSR group than in the BT Group (p

Abstract Manufacturability evaluation is an effective way to shorten the development period, optimize manufacturing processes, and reduce product costs. The manufacturability of a product depends on the processing ability of specific manufacturing resources. The development of a manufacturing resources model serves as the foundation for manufacturability evaluation. To better utilize the information on manufacturing resources, this study adopted a hybrid approach by integrating the fuzzy c-means clustering algorithm and the genetic algorithm to group manufacturing resources based on manufacturing and geometric features. The information model of manufacturing resources was built by using the object-oriented method. Subsequently, the framework to evaluate manufacturing capability based on manufacturing resources was defined. Further, an application sample was exploited and its results were analyzed. The results of the subgroup showed that the hybrid algorithm was reliable and valid and helped improve the overall performance of the company chosen for this study. The proposed approach enhanced feasibility in decision-making and facilitated the management to make more informed decisions.

Abstract Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 [95% CI: 0.75–0.91, p

Abstract The purposes are to develop the patent data profoundly, control the data access process effectively, and protect the patent information and content. The traditional patent review systems are analyzed. For the present patent data security and privacy protection technologies and algorithms, the patent information data are stored on different block nodes after data fragmentation using blockchain technology. Then the data are shared using the data encryption algorism. In this way, data access control can be restricted to particular users. Finally, a patent data protection scheme based on privacy protection is proposed. The security of the scheme and the model performance are verified through simulation experiments. The time required to encrypt 10 MB files with 64-bit and 128-bit data is 35 ms and 105 ms, respectively. The proposed re-encryption algorithm only needs 1 s to decrypt 64 KB data, and only 1% of the data needs asymmetric encryption. This greatly reduces the computational overhead of encryption. Results demonstrate that the system can effectively control the access methods of users, efficiently protect the personal privacy and patent content of patent applicants, and reduce the patent office cloud computing overhead using the local resources of branches. The distributed storage methods can reduce the cloud system interaction of the patent office, thereby greatly improving the speed of encryption and ensuring data security. Compared with the state of the art methods, the proposed patent data access and protection system based on blockchain technology have greater advantages in data security and model performance. The research results can provide a research foundation and practical value for the protection and review systems of patent data.

Abstract Flash glucose monitoring (FGM) was introduced in China in 2016, and it might improve HbA1c measurements and reduce glycaemic variability during T1DM therapy. A total of 146 patients were recruited from October 2018 to September 2019 in Liaocheng. The patients were randomly divided into the FGM group or self-monitoring blood glucose (SMBG) group. Both groups wore the FGM device for multiple 2-week periods, beginning with the 1st, 24th, and 48th weeks for gathering data, while blood samples were also collected for HbA1c measurement. Dietary guidance and insulin dose adjustments were provided to the FGM group patients according to their Ambulatory Glucose Profile (AGP) and to the SMBG group patients according to their SMBG measurements taken 3–4 times daily. All of the participants underwent SMBG measurements on the days when not wearing the FGM device. At the final visit, HbA1c, time in range (TIR), duration of hypoglycaemia and the number of diabetic ketoacidosis (DKA) events were taken as the main endpoints. There were no significant difference in the baseline characteristics of the two groups. At 24 weeks, the HbA1c level of the FGM group was 8.16 ± 1.03%, which was much lower than that of the SMBG group (8.68 ± 1.01%) (p = 0.003). The interquartile range (IQR), mean blood glucose (MBG), and the duration of hypoglycaemia in the FGM group also showed significant declines, compared with the SMBG group (p

Abstract We demonstrate that neural networks that process noisy data can learn to exploit, when available, access to auxiliary noise that is correlated with the noise on the data. In effect, the network learns to use the correlated auxiliary noise as an approximate key to decipher its noisy input data. An example of naturally occurring correlated auxiliary noise is the noise due to decoherence. Our results could, therefore, also be of interest, for example, for machine-learned quantum error correction.

Abstract Higher magnetic fields are always favoured in the magnetoplasmadynamic thruster (MPDT) due to its superior control of the plasma profile and acceleration process. This paper introduces the world's first integrated study on the 150 kW level AF-MPDT equipped with a superconductive coil. A completely new way of using superconducting magnet technology to confine plasma with high energy and extremely high temperatures is proposed. Using the PIC method of microscopic particle simulation, the plasma magnetic nozzle effect and performance of the MPDT under different magnetic-field conditions were studied. The integrated experiment used demonstrated that, in conjunction with the superconducting coil, greater homogeneity and a stronger magnetic field not only caused more even cathode ablation and improved its lifespan but also improved the performance of the MPDT (maximum thrust was 4 N at 150 kW, 0.56 T). Maximum thrust efficiency reached 76.6% and the specific impulse reached 5714 s.

Abstract A promising technique of discovering disease biomarkers is to measure the relative protein abundance in multiple biofluid samples through liquid chromatography with tandem mass spectrometry (LC-MS/MS) based quantitative proteomics. The key step involves peptide feature detection in the LC-MS map, along with its charge and intensity. Existing heuristic algorithms suffer from inaccurate parameters and human errors. As a solution, we propose PointIso, the first point cloud based arbitrary-precision deep learning network to address this problem. It consists of attention based scanning step for segmenting the multi-isotopic pattern of 3D peptide features along with the charge, and a sequence classification step for grouping those isotopes into potential peptide features. PointIso achieves 98% detection of high-quality MS/MS identified peptide features in a benchmark dataset. Next, the model is adapted for handling the additional ‘ion mobility’ dimension and achieves 4% higher detection than existing algorithms on the human proteome dataset. Besides contributing to the proteomics study, our novel segmentation technique should serve the general object detection domain as well.

Abstract The aim of this study was to analyze the role of blood biomarkers regarding preoperative inflammation and coagulation in predicting the postoperative in-hospital mortality of patients with type A acute aortic dissection (AAD). A total of 206 patients with type A AAD who had received surgical treatment were enrolled in this study. Patients were divided into two groups: the death group (28 patients who died during hospitalization) and the survival group (178 patients). Peripheral blood samples were collected before anesthesia induction. Preoperative levels of D-dimer, fibrinogen (FIB), platelet (PLT), white blood cells (WBC) and neutrophil (NEU) were compared between the two groups. Univariable and multivariable logistic regression analysis were utilized to identify the independent risk factors for postoperative in-hospital deaths of patients with type A AAD. Receiver operating characteristic (ROC) curve were used to analyze the predictive value of these indices in the postoperative in-hospital mortality of the patients. Univariable logistic regression analysis showed that the P values of the five parameters including D-dimer, FIB, PLT, WBC and NEU were all less than 0.1, which may be risk factors for postoperative in-hospital deaths of patients with type A AAD. Further multivariable logistic regression analysis indicated that higher preoperative D-dimer and WBC levels were independent risk factors for postoperative in-hospital mortality of patients with type A AAD. ROC curve analysis indicated that application of combining FIB and PLT could improve accuracy in prediction of postoperative in-hospital mortality in patients with type A AAD. Both preoperative D-dimer and WBC in patients with type A AAD may be used as independent risk factors for the postoperative in-hospital mortality of such patients. The combination of FIB and PLT may improve the accuracy of clinical prognostic assessment.

Abstract This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), d-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, d-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, d-dimer, and FDP than the controls (P

Abstract Perfectly controlled molecules are at the forefront of the quest to explore chemical reactivity at ultra low temperatures. Here, we investigate for the first time the formation of the long-lived intermediates in the time-dependent scattering of cold bialkali $$^{23}\hbox {Na}^{87}$$ 23 Na 87 Rb molecules with and without the presence of infrared trapping light. During the nearly 50 nanoseconds mean collision time of the intermediate complex, we observe unconventional roaming when for a few tens of picoseconds either NaRb or $$\hbox {Na}_2$$ Na 2 and $$\hbox {Rb}_2$$ Rb 2 molecules with large relative separation are formed before returning to the four-atom complex. We also determine the likelihood of molecular loss when the trapping laser is present during the collision. We find that at a wavelength of 1064 nm the $$\hbox {Na}_2\hbox {Rb}_2$$ Na 2 Rb 2 complex is quickly destroyed and thus that the $$^{23}\hbox {Na}^{87}$$ 23 Na 87 Rb molecules are rapidly lost.

Abstract Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45–79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29–0.96, P trend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (P interaction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15–0.76, P trend = 0.02), compared to 1.24 (95% CI 0.46–3.35, P trend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men.

Abstract This was a retrospective analysis of a total of 625 r-ICSI cycles using freeze-all-embryos and embryo transfers (ET) in subsequent cryopreservation-warming cycles to determine the effect of the ET method for day 1 rescue intracytoplasmic sperm injection cycles (r-ICSI). Two methods were used: in method 1, cleavage-stage embryos were frozen and were directly transferred in a subsequent cryopreservation-warming cycle (r-ICSI frozen cleavage), and 144 cleavage-stage ETs occurred. Similarly, in method 2, there were 188 blastocyst-stage ETs (r-ICSI frozen blast) performed. The live birth rate (LBR) for r-ICSI frozen blast was better than that for r-ICSI frozen cleavage in calculation of ET cycles (19.44% vs. 37.77%) and also remained better after the use of logistic regression analysis (OR = 2.721, 95% CI 1.604–4.616). Conservative cumulative LBR were compared between r-ICSI frozen cleavage and r-ICSI frozen blast with regard to oocyte retrieval cycles (17.39% vs. 15.30%). The same results were obtained for conservative cumulative LBR after logistic regression analysis (OR = 0.925, 95% CI 0.557–1.535). The results of this study confirmed that it was valuable to perform r-ICSI if using freeze-all-embryos. Further, r-ICSI embryos were cultured to blastocyst stage, cryopreserved, and used in subsequent cryopreservation-warming cycles, which was an effective embryo transfer strategy and obtained satisfactory results.

Abstract Insecticides, especially pyrethroids, are the most important in the insect pest control and preventing insect vector-borne human diseases. However, insect pests, including mosquitoes, have developed resistance in the insecticides that used against them. Cytochrome P450s are associated with insecticide resistance through overexpression and detoxification mechanisms in insect species. In this study, we utilized a powerful tool, the RNAi technique, to determine the roles of key P450 genes overexpressed in permethrin resistant mosquitoes that confer insecticide resistance to unravel the molecular basis of resistance mechanisms in the mosquito Culex quinquefasciatus. The results showed that knockdown of 8 key P450 genes using RNAi techniques significantly decreased resistance to permethrin in resistant mosquitoes. In silico modeling and docking analysis further revealed the potential metabolic function of overexpressed P450 genes in the development of insecticide resistance in mosquitoes. These findings not only highlighted the functional importance of these P450 genes in insecticide resistance, but also revealed that overexpression of multiple P450 genes was responsible for the high levels of insecticide resistance in a mosquito population of Culex quinquefasciatus.

Abstract Glycyrrhiza, a genus of perennial medicinal herbs, has been traditionally used to treat human diseases, including respiratory disorders. Functional analysis of genes involved in the synthesis, accumulation, and degradation of bioactive compounds in these medicinal plants requires accurate measurement of their expression profiles. Reverse transcription quantitative real-time PCR (RT-qPCR) is a primary tool, which requires stably expressed reference genes to serve as the internal references to normalize the target gene expression. In this study, the stability of 14 candidate reference genes from the two congeneric species G. uralensis and G. inflata, including ACT, CAC, CYP, DNAJ, DREB, EF1, RAN, TIF1, TUB, UBC2, ABCC2, COPS3, CS, R3HDM2, were evaluated across different tissues and throughout various developmental stages. More importantly, we investigated the impact of interactions between tissue and developmental stage on the performance of candidate reference genes. Four algorithms, including geNorm, NormFinder, BestKeeper, and Delta Ct, were used to analyze the expression stability and RefFinder, a comprehensive software, provided the final recommendation. Based on previous research and our preliminary data, we hypothesized that internal references for spatio-temporal gene expression are different from the reference genes suited for individual factors. In G. uralensis, the top three most stable reference genes across different tissues were R3HDM2, CAC and TUB, while CAC, CYP and ABCC2 were most suited for different developmental stages. CAC is the only candidate recommended for both biotic factors, which is reflected in the stability ranking for the spatio (tissue)-temporal (developmental stage) interactions (CAC, R3HDM2 and DNAJ). Similarly, in G. inflata, COPS3, R3HDM2 and DREB were selected for tissues, while RAN, COPS3 and CS were recommended for developmental stages. For the tissue-developmental stage interactions, COPS3, DREB and ABCC2 were the most suited reference genes. In both species, only one of the top three candidates was shared between the individual factors and their interactions, specifically, CAC in G. uralensis and COPS3 in G. inflata, which supports our overarching hypothesis. In summary, spatio-temporal selection of reference genes not only lays the foundation for functional genomics research in Glycyrrhiza, but also facilitates these traditional medicinal herbs to reach/maximize their pharmaceutical potential.

Abstract To develop age- and sex-specific physical fitness reference standards and express the age- and sex-related differences using standardized effect sizes for Chinese children and adolescents. A total of 85,535 children and adolescents (48.7% girls) aged 7–18 years were recruited from six geographical divisions of China using a stratified randomized cluster sampling method. Seven physical fitness items including grip strength, standing long jump, 30-s sit-ups, sit and reach, 50-m dash, 20-s repeated straddling, and 20-m SRT were measured following a standardized procedure. Percentile curves for each physical fitness test were calculated using the LMS. Age- and sex-related differences were expressed as standardized effect sizes. We observed that the performance improved with age along with the analyzed percentiles in all tests. Boys had higher values compared to girls in all the physical fitness items except for sit and reach test, where girls showed better performance in all analyzed percentiles. Also, the sex differences increased with ages except sit and reach. There is a need for a differentiated approach in the physical education class in terms of adjustment of physical activity based on sex, level of fitness abilities in China.

Abstract As one of the largest transcription factor family, basic helix-loop-helix (bHLH) transcription factor family plays an important role in plant metabolism, physiology and growth. Berry color is one of the important factors that determine grape quality. However, the bHLH transcription factor family’s function in anthocyanin synthesis of grape berry has not been studied systematically. We identified 115 bHLH transcription factors in grape genome and phylogenetic analysis indicated that bHLH family could be classified into 25 subfamilies. First, we screened six candidate genes by bioinformatics analysis and expression analysis. We found one of the candidate genes VdbHLH037 belonged to III (f) subfamily and interacted with genes related to anthocyanin synthesis through phylogenetic analysis and interaction network prediction. Therefore, we speculated that VdbHLH037 participated in the anthocyanin synthesis process. To confirm this, we transiently expressed VdbHLH037 in grape and Arabidopsis transformation. Compared with the control, transgenic materials can accumulate more anthocyanins. These results provide a good base to study the function of the VdbHLH family in anthocyanin synthesis of grape berry.

Abstract The purpose of this work is to evaluate the performance of applying patient dosimetric information induced by individual uniform-intensity radiation fields in organ-at risk (OAR) dose-volume histogram (DVH) prediction, and extend to DVH prediction of planning target volume (PTV). Ninety nasopharyngeal cancer intensity-modulated radiation therapy (IMRT) plans and 60 rectal cancer volumetric modulated arc therapy (VMAT) plans were employed in this study. Of these, 20 nasopharyngeal cancer cases and 15 rectal cancer cases were randomly selected as the testing data. The DVH prediction was performed using two methods. One method applied the individual dose-volume histograms (IDVHs) induced by a series of fields with uniform-intensity irradiation and the other method applied the distance-to-target histogram and the conformal-plan-dose-volume histogram (DTH + CPDVH). The determination coefficient R2 and mean absolute error (MAE) were used to evaluate DVH prediction accuracy. The PTV DVH prediction was performed using the IDVHs. The PTV dose coverage was evaluated using D 98 , D 95 , D 1 and uniformity index (UI). The OAR dose was compared using the maximum dose, V 30 and V 40 . The significance of the results was examined with the Wilcoxon signed rank test. For PTV DVH prediction using IDVHs, the clinical plan and IDVHs prediction method achieved mean UI values of 1.07 and 1.06 for nasopharyngeal cancer, and 1.04 and 1.05 for rectal cancer, respectively. No significant difference was found between the clinical plan results and predicted results using the IDVHs method in achieving PTV dose coverage (D 98, D 95, D 1 and UI) for both nasopharyngeal cancer and rectal cancer (p-values ≥ 0.052). For OAR DVH prediction, no significant difference was found between the IDVHs and DTH + CPDVH methods for the R2, MAE, the maximum dose, V 30 and V 40 (p-values ≥ 0.087 for all OARs). This work evaluates the performance of dosimetric information of several individual fields with uniform-intensity radiation for DVH prediction, and extends its application to PTV DVH prediction. The results indicated that the IDVHs method is comparable to the DTH + CPDVH method in accurately predicting the OAR DVH. The IDVHs method quantified the input features of the PTV and showed reliable PTV DVH prediction, which is helpful for plan quality evaluation and plan generation.

Abstract Controversy and challenges remain regarding the cognition of lung adenocarcinomas presented as subcentimeter ground glass nodules (GGNs). Postoperative lymphatic involvement or intrapulmonary metastasis is found in approximately 15% to 20% of these cases. This study aimed to develop and validate a radiomics signature to identify the invasiveness of lung adenocarcinoma appearing as subcentimeter ground glass nodules. We retrospectively enrolled 318 subcentimeter GGNs with histopathology-confirmed adenocarcinomas in situ (AIS), minimally invasive adenocarcinomas (MIA) and invasive adenocarcinomas (IAC). The radiomics features were extracted from manual segmentation based on contrast-enhanced CT (CECT) and non-contrast enhanced CT (NCECT) images after imaging preprocessing. The Lasso algorithm was applied to construct radiomics signatures. The predictive performance of radiomics models was evaluated by receiver operating characteristic (ROC) analysis. A radiographic-radiomics combined nomogram was developed to evaluate its clinical utility. The radiomics signature on CECT (AUC: 0.896 [95% CI 0.815–0.977]) performed better than the radiomics signature on NCECT data (AUC: 0.851[95% CI 0.712–0.989]) in the validation set. An individualized prediction nomogram was developed using radiomics model on CECT and radiographic model including type, shape and vascular change. The C index of the nomogram was 0.915 in the training set and 0.881 in the validation set, demonstrating good discrimination. Decision curve analysis (DCA) revealed that the proposed model was clinically useful. The radiomics signature built on CECT could provide additional benefit to promote the preoperative prediction of invasiveness in patients with subcentimeter lung adenocarcinomas.

Abstract Microfluidic focusing of particles (both synthetic and biological), which enables precise control over the positions of particles in a tightly focused stream, is a prerequisite step for the downstream processing, such as detection, trapping and separation. In this study, we propose a novel hydrodynamic focusing method by taking advantage of open v-shaped microstructures on a glass substrate engraved by femtosecond pulse (fs) laser. The fs laser engraved microstructures were capable of focusing polystyrene particles and live cells in rectangular microchannels at relatively low Reynolds numbers (Re). Numerical simulations were performed to explain the mechanisms of particle focusing and experiments were carried out to investigate the effects of groove depth, groove number and flow rate on the performance of the groove-embedded microchannel for particle focusing. We found out that 10-µm polystyrene particles are directed toward the channel center under the effects of the groove-induced secondary flows in low-Re flows, e.g. Re

Abstract Novel coronavirus 2019 (COVID-19) infection is a global public health issue, that has now affected more than 200 countries worldwide and caused a second wave of pandemic. Severe adult respiratory syndrome-CoV-2 (SARS-CoV-2) pneumonia is associated with a high risk of mortality. However, prognostic factors predicting poor clinical outcomes of individual patients with SARS-CoV-2 pneumonia remain under intensive investigation. We conducted a retrospective, multicenter study of patients with SARS-CoV-2 who were admitted to four hospitals in Wuhan, China from December 2019 to February 2020. Mortality at the end of the follow up period was the primary outcome. Factors predicting mortality were also assessed and a prognostic model was developed, calibrated and validated. The study included 492 patients with SARS-CoV-2 who were divided into three cohorts: the training cohort (n = 237), the validation cohort 1 (n = 120), and the validation cohort 2 (n = 135). Multivariate analysis showed that five clinical parameters were predictive of mortality at the end of follow up period, including advanced age [odds ratio (OR), 1.1/years increase (p

Abstract We evaluated the feasibility and image quality of prospective electrocardiography (ECG)-triggered coronary computed tomography angiography (CCTA) using a body surface area (BSA) protocol for contrast-medium (CM) administration on both second- and third-generation scanners (Flash and Force CT), without using heart rate control. One-hundred-and-eighty patients with suspected coronary heart disease undergoing CCTA were divided into groups A (BSA protocol for CM on Flash CT), B (body mass index (BMI)-matched patients; BMI protocol for CM on Flash CT), and C (BMI-matched patients; BSA protocol for CM on Force CT). Patient characteristics, quantitative and qualitative measures, and radiation dose were compared between groups A and B, and A and C. Of the 180 patients, 99 were male (median age, 62 years). Average BSA in groups A, B, and C was 1.80 ± 0.17 m2, 1.74 ± 0.16 m2, and 1.64 ± 0.17 m2, respectively, with groups A and C differing significantly (P 250 HU, average scores > 4) achieved slightly lower diagnostic image quality than group B. The BSA protocol for CM administration was feasible in both Flash and Force CT, and therefore may be valuable in clinical practice.

Abstract The effect of conical intersections (CIs) on electronic relaxation, transitions from excited states to ground states, is well studied, but their influence on hyperfine quenching in a reactant molecule is not known. Here, we report on ultracold collision dynamics of the hydroxyl free-radical OH with Sr atoms leading to quenching of OH hyperfine states. Our quantum-mechanical calculations of this process reveal that quenching is efficient due to anomalous molecular dynamics in the vicinity of the conical intersection at collinear geometry. We observe wide scattering resonance features in both elastic and inelastic rate coefficients at collision energies below $$k_{\text {B}}\times 10 \, \hbox {mK}$$ k B × 10 mK . They are identified as either p- or d-wave shape resonances. We also describe the electronic potentials relevant for these non-reactive collisions, their diabatization procedure, as well as the non-adiabatic coupling between the diabatic potentials near the CIs.

Abstract miRNAs have been reported to be stably detectable in plasma and to function as potent biomarkers in multiple cancers. The study aimed to evaluate the expression of candidate circulating miRNAs in patients with small cell lung cancer (SCLC) to identify potential noninvasive biomarkers. The expression of five miRNAs (miR-92b, miR-146a, miR-375, miR-1224, and miR-1246) was significantly upregulated in plasma after chemoresistance induction. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve (AUC) values of miR-92b and miR-375 were 0.766 and 0.791, respectively. The data demonstrated that among the five miRNAs assessed, these two miRNAs had better diagnostic accuracy for monitoring drug resistance. In addition, miR-92b and miR-375 levels were decreased after effective chemotherapy. Furthermore, Kaplan–Meier survival analysis confirmed that high expression of miR-92b and miR-375 was closely related to shorter progression-free survival (PFS) in SCLC patients. In conclusion, these findings indicate that circulating miR-92b and miR-375 might be ideal noninvasive biomarkers for monitoring drug resistance during chemotherapy and evaluating the prognosis of patients with SCLC.

Abstract A flexible and stable biomimetic SERS substrate was successfully fabricated by depositing gold (Au) nanoislands on the dragonfly wings (DW) via a simple DC magnetron sputtering system. Characterizations of the Au/DW nanostructure indicated that the optimum Au/DW-45 (sputtering time was 45 min) substrate owns high sensitivity, good stability and outstanding reproducibility. The limit of detection (LOD) for Rhodamine 6 G (R6G) was as low as 10−7 M and enhancement factor (EF) was calculated to be 2.8 × 106. 70-day-duration stability tests showed that Raman intensity of R6G reduced only by 12.9% after aging for 70 days. The maximum relative standard deviations (RSD) of SERS intensities from 100 positions of Au/DW-45 substrate were less than 8.3%, revealing outstanding uniformity and reproducibility. Moreover, the flexible Au/DW-45 bioscaffold arrays were employed to solve the vital problem of pesticide residues. By directly sampling from tomato peels via a “press and peel off” approach, cypermethrin has been rapidly and reliably determined with a LOD centered at 10−3 ng/cm2 and a correlation coefficient (R2) of 0.987. The positive results demonstrated that the Au-based DW biomimetic arrays may offer an efficient SERS platform for the identification of various pesticide residues on real samples.

Abstract Tumor protein p53 acts as a trans-activator that negatively regulates cell division by controlling a set of genes required for cell cycle regulation, making it a tumor suppressor in different types of tumors. Because the transcriptional activity of p53 plays an important role in the occurrence and development of tumors, reactivation of p53 transcriptional activity has been sought as a novel cancer therapeutic strategy. There is great interest in developing high-throughput assays to identify inhibitors of molecules that bind the transcription-activation domain of p53, especially for wt p53-containing tumors. In the present study, taking MDM2 as an example, a novel amplified luminescent proximity homogeneous assay (AlphaLISA) was modified from a binding competition assay to detect the interactions between the transcription-activation domain of p53 and its ligands. This assay can be adapted as a high-throughput assay for screening new inhibitors. A panel of well-known p53-MDM2 binding inhibitors was used to validate this method, and demonstrated its utility, sensitivity and robustness. In summary, we have developed a novel protein-protein interaction detection immunoassay that can be used in a high-throughput format to screen new drug candidates for reactivation of p53. This assay has been successfully validated through a series of p53-MDM2 binding inhibitors.

Abstract Hypoxia is a characteristic of locally advanced solid tumors, resulting from an imbalance between oxygen consumption and supply. In hypoxic solid tumors, an increased expression of nitroreductase (NTR) is detected, therefore, the development of NTR-targeted fluorescent probes to selectively and efficiently detect hypoxia in vivo is of utmost importance. In this study, a probe (1) has been designed and tested for effective optical detection of NTR in vitro and in vivo. The reduction of probe (1), catalyzed by NTR, resulted in changes of the electron-withdrawn nitrogen group into an electron-donation amino group. In addition, breakage of the O-C bond ensured selective fluorescence enhancement. The in vitro response towards exogenous NTR, from rat liver microsomes, resulted in the optical enhancement during the detection process. In vivo imaging of caerorhabditis elegans (C.elegan) further confirmed the detection of NTR by probe (1). Moreover, probe (1) was successfully used for the detection of hypoxia in both HI5 cells, and a murine tumor model, which demonstrates the potential of probe (1) for application in fluorescence bioimaging studies, and tumor hypoxia diagnosis.

Abstract The chloride/phosphate ratio (Cl/PO4) has been suggested to have a role in primary hyperparathyroidism (PHPT), but the associations between Cl/PO4 combined with ALP level and PHPT has not been well-studied. Our aim was to investigate the predictive value of combination Cl/PO4 with ALP for PHPT. A cross-sectional retrospective analysis was conducted to examine 172 patients diagnosed with PHPT categorized into two groups: normocalcaemic primary hyperparathyroidism (NPHPT) group and hypercalcaemia PHPT group. We found that Cl/PO4 levels and ALP levels in the NPHPT and hypercalcaemia PHPT group were both significantly higher than normal controls. Cl/PO4 and ALP levels were an independent risk factor for PHPT. Cl/PO4 combined with ALP increased the receiver-operating characteristic curves (ROC-AUC) and the diagnostic value in NPHPT and hypercalcaemia PHPT group (0.913; 95% CI, 0.744–1.000 and 0.932; 95% CI, 0.897–0.966, respectively), specificity of 92.8% and sensitivity of 98%. In conclusion, combination Cl/PO4 with ALP might be a low-cost, simple, available predictive marker of PHPT in Chinese individuals, particularly Chinese remote region where the method used to measure PTH cannot be done. Moreover, due to serum calcium level in NPHPT, Cl/PO4 combined with ALP level measurement have great potential to predict significant occurrence of NPHPT.

Abstract Periodontal diseases manifest by the formation of deep pockets between the gingiva and teeth where multispecies bacterial biofilms flourish, causing inflammation and bone loss. Epithelial cell receptor αvβ6 integrin that regulates inflammation by activating the anti-inflammatory cytokine transforming growth factor-β1, is highly expressed in healthy junctional epithelium that connects the gingiva to the tooth enamel. However, its expression is attenuated in human periodontal disease. Moreover, Itgb6 −/− mice display increased periodontal inflammation compared to wild-type mice. We hypothesized that bacterial biofilms present in the periodontal pockets suppress αvβ6 integrin levels in periodontal disease and that this change aggravates inflammation. To this end, we generated three-week-old multi-species oral biofilms in vitro and treated cultured gingival epithelial cells (GECs) with their extracts. The biofilm extracts caused suppression of β6 integrin expression and upregulation of pro-inflammatory cytokines, including interleukin-1β and -6. Furthermore, GECs with β6 integrin siRNA knockdown showed increased interleukin-1β expression, indicating that αvβ6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed β6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate αvβ6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease.

Abstract The performance of diagnostic tests in intervention trials of Helicobacter pylori (H.pylori) eradication is crucial, since even minor inaccuracies can have major impact. To determine the cut-off point for 13C-urea breath test (13C-UBT) and to assess if it can be further optimized by serologic testing, mathematic modeling, histopathology and serologic validation were applied. A finite mixture model (FMM) was developed in 21,857 subjects, and an independent validation by modified Giemsa staining was conducted in 300 selected subjects. H.pylori status was determined using recomLine H.pylori assay in 2,113 subjects with a borderline 13C-UBT results. The delta over baseline-value (DOB) of 3.8 was an optimal cut-off point by a FMM in modelling dataset, which was further validated as the most appropriate cut-off point by Giemsa staining (sensitivity = 94.53%, specificity = 92.93%). In the borderline population, 1,468 subjects were determined as H.pylori positive by recomLine (69.5%). A significant correlation between the number of positive H.pylori serum responses and DOB value was found (rs = 0.217, P

Abstract Juvenile hormone epoxide hydrolase (JHEH) has attracted great interest because of its critical role in the regulation of juvenile hormone (JH) in insects. In this study, one JHEH gene from Apolygus lucorum (AlucJHEH) was characterized in terms of deduced amino acid sequence, phylogeny, homology modeling and docking simulation. The results reveals a conserved catalytic mechanism of AlucJHEH toward JH. Our study also demonstrates that the mRNA of AlucJHEH gene was detectable in head, thorax and abdomen from all life stages. To functionally characterize the AlucJHEH gene, three fragments of double-stranded RNAs (dsRNAs) were designed to target different regions of the sequence. Injection of 3rd nymphs with dsRNA fragments successfully knocked down the target gene expression, and a significantly decreased survival rate was observed, together with a molting block, These findings confirm the important regulatory roles of AlucJHEH in A. lucorum and indicate this gene as a promising target for future hemipterans pest control.