PHB3 interacts with BRI1 and BAK1 to mediate brassinosteroid signal transduction in Arabidopsis and tomato.

Brassinosteroids (BRs) are plant hormones that are essential in plant growth and development. BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1 ASSOCIATED RECEPTOR KINASE 1 (BAK1), which are located on the plasma membrane, function as co-receptors that accept and transmit BR signals. PROHIBITIN 3 (PHB3) was identified in both BRI1 and BAK1 complexes by affinity purification and LC-MS/MS analysis. Biochemical data showed that BRI1/BAK1 interacted with PHB3 in vitro and in vivo. BRI1/BAK1 phosphorylated PHB3 in vitro. When the Thr-80 amino acid in PHB3 was mutated to Ala, the mutant protein was not phosphorylated by BRI1 and the mutant protein interaction with BRI1 was abolished in the yeast two-hybrid assay. BAK1 did not phosphorylate the mutant protein PHB3T54A . The loss-of-function phb3 mutant showed a weaker BR signal than the wild-type. Genetic analyses revealed that PHB3 is a BRI1/BAK1 downstream substrate that participates in BR signalling. PHB3 has five homozygous in tomato, and we named the closest to AtPHB3 as SlPHB3.1. Biochemical data showed that SlBRI1/SlSERK3A/SlSERK3B interacted with SlPHB3.1 and SlPHB3.3. The CRISPR-Cas9 method generated slphb3.1 mutant led to a BR signal stunted relatively in tomatoes. PHB3 is a new component of the BR signal pathway in both Arabidopsis and tomato.

A deep learning-based 3D Prompt-nnUnet model for automatic segmentation in brachytherapy of postoperative endometrial carcinoma.

PURPOSE: To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). METHODS AND MATERIALS: On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). RESULTS: The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96 ± 0.02, 0.91 ± 0.02, and 0.83 ± 0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73 ± 0.95, 8.18 ± 4.84, and 2.11 ± 0.50, respectively. The mean HD95% values (mm) were 1.66 ± 1.11, 3.07 ± 0.94, and 1.35 ± 0.55, respectively. The mean IoUs were 0.92 ± 0.04, 0.84 ± 0.03, and 0.71 ± 0.09, respectively. A delineation time < 2.35 s per structure in the new model was observed, which was available to save clinician time. CONCLUSION: The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.

Measuring the worldwide spread of COVID-19 using a comprehensive modeling method.

BACKGROUND: With the global spread of COVID-19, detecting high-risk countries/regions timely and dynamically is essential; therefore, we sought to develop automatic, quantitative and scalable analysis methods to observe and estimate COVID-19 spread worldwide and further generate reliable and timely decision-making support for public health management using a comprehensive modeling method based on multiple mathematical models. METHODS: We collected global COVID-19 epidemic data reported from January 23 to September 30, 2020, to observe and estimate its possible spread trends. Countries were divided into three outbreak levels: high, middle, and low. Trends analysis was performed by calculating the growth rate, and then country grouping was implemented using group-based trajectory modeling on the three levels. Individual countries from each group were also chosen to further disclose the outbreak situations using two predicting models: the logistic growth model and the SEIR model. RESULTS: All 187 observed countries' trajectory subgroups were identified using two grouping strategies: with and without population consideration. By measuring epidemic trends and predicting the epidemic size and peak of individual countries, our study found that the logistic growth model generally estimated a smaller epidemic size than the SEIR model. According to SEIR modeling, confirmed cases in each country would take an average of 9-12 months to reach the outbreak peak from the day the first case occurred. Additionally, the average number of cases at the peak time will reach approximately 10-20% of the countries' populations, and the countries with high trends and a high predicted size must pay special attention and implement public health interventions in a timely manner. CONCLUSIONS: We demonstrated comprehensive observations and predictions of the COVID-19 outbreak in 187 countries using a comprehensive modeling method. The methods proposed in this study can measure COVID-19 development from multiple perspectives and are generalizable to other epidemic diseases. Furthermore, the methods also provide reliable and timely decision-making support for public health management.

Ultrasensitive Antibiotic Perceiving Based on Aptamer-Functionalized Ultraclean Graphene Field-Effect Transistor Biosensor.

Antibiotics are powerful tools to treat bacterial infections, but antibiotic pollution is becoming a severe threat to the effective treatment of human bacterial infections. The detection of antibiotics in water has been a crucial research area for bioassays in recent years. There is still an urgent need for a simple ultrasensitive detection approach to achieve accurate antibiotic detection at low concentrations. Herein, a field-effect transistor (FET)-based biosensor was developed using ultraclean graphene and an aptamer for ultrasensitive tetracycline detection. Using a newly designed camphor-rosin clean transfer (CRCT) scheme to prepare ultraclean graphene, the carrier mobility of the FET is found to be improved by more than 10 times compared with the FET prepared by the conventional PMMA transfer (CPT) method. Based on the FET, aptamer-functionalized transistor antibiotic biosensors were constructed and characterized. A dynamic detection range of 5 orders of magnitude, a sensitivity of 21.7 mV/decade, and a low detection limit of 100 fM are achieved for the CRCT-FET biosensors with good stability, which are much improved compared with the biosensor prepared by the CPT method. The antibiotic sensing and sensing performance enhancement mechanisms for the CRCT-FET biosensor were studied and analyzed based on experimental results and a biosensing model. Finally, the CRCT-FET biosensor was verified by detecting antibiotics in actual samples obtained from the entrances of Bohai Bay.

Poly-l-Lysine-Modified Graphene Field-Effect Transistor Biosensors for Ultrasensitive Breast Cancer miRNAs and SARS-CoV-2 RNA Detection.

(Mi)RNAs are important biomarkers for cancers diagnosis and pandemic diseases, which require fast, ultrasensitive, and economical detection strategies to quantitatively detect exact (mi)RNAs expression levels. The novel coronavirus disease (SARS-CoV-2) has been breaking out globally, and RNA detection is the most effective way to identify the SARS-CoV-2 virus. Here, we developed an ultrasensitive poly-l-lysine (PLL)-functionalized graphene field-effect transistor (PGFET) biosensor for breast cancer miRNAs and viral RNA detection. PLL is functionalized on the channel surface of GFET to immobilize DNA probes by the electrostatic force. The results show that PGFET biosensors can achieve a (mi)RNA detection range of five orders with a detection limit of 1 fM and an entire detection time within 20 min using 2 µL of human serum and throat swab samples, which exhibits more than 113% enhancement in terms of sensitivity compared to that of GFET biosensors. The performance enhancement mechanisms of PGFET biosensors were comprehensively studied based on an electrical biosensor theoretical model and experimental results. In addition, the PGFET biosensor was applied for the breast cancer miRNA detection in actual serum samples and SARS-CoV-2 RNA detection in throat swab samples, providing a promising approach for rapid cancer diagnosis and virus screening.

Sex differences involved in persistent atrial fibrillation recurrence after radiofrequency ablation.

BACKGROUND: In recent years, the difference in outcomes of radiofrequency catheter ablation (RFCA) in persistent atrial fibrillation patients has risen. In particular, biological sex seems involved in a different response to the AF ablation procedure. In our study, we analyzed the AF recurrences after RFCA assessing the other association between male/female patients with the outcomes. METHODS: We enrolled 106 patients (74.5% men) with persistent atrial fibrillation with scheduled follow-up. The baseline clinical characteristics and AF recurrence after RFCA were compared between men and women. Cox regression analyses were performed to determine the risk predictors of AF recurrence. RESULTS: The proportion of RFCA in women was lower than that in men. Men with persistent AF were younger than women (58.6 ± 10.4 years vs. 65.1 ± 8.7 years, respectively; p = 0.003). The left atrium (LA) diameter was higher in males (43.7 ± 4.6 mm vs. 41.3 ± 5.5 mm; p = 0.028), and the level of left heart ejection fraction (LVEF) was higher in females (59.4 ± 6.9% vs. 64.1 ± 5.5%; p = 0.001). Sex differences in AF recurrence after RFCA were significant during the median 24.4-month (interquartile range: 15.2-30.6 months) follow-up period, and the recurrence rate of AF in women was significantly higher than that in men (p = 0.005). Univariable Cox regression analysis showed that female sex was a risk factor for persistent AF recurrence after RFCA [HR: 2.099 (1.087-4.053)]. Univariate Cox regression analysis revealed that non-PV ablation not associated with AF recurrence [HR: 1.003 (0.516-1.947)]. CONCLUSION: In a monocentric cohort of persistent AF patients, the female biological sex was associated with a higher risk of AF recurrence after RFCA.

Nitrogen Uptake and Distribution in Different Chinese Cabbage Genotypes under Low Nitrogen Stress.

In order to understand the effects of low nitrogen (LN) stress on the growth and development in different genotypes of Chinese cabbage, the L40 genotype with high nitrogen utilization and the L14 genotype with LN utilization were selected as experimental materials. Field experiments and indoor hydroponic methods were used to study the different responses of two Chinese cabbage genotypes to low nitrogen levels. In this study, we also analyzed the genome-wide gene expression profiles of L40 and L14 in response to LN stress by high-throughput RNA sequencing technology. The results reveal that the L40 root system responds better to LN compared with L14. After LN stress, L40 can effectively absorb and transport NO3- and store it in the ground. It is precisely because of this characteristic of the L40 genotype that LN treatment did not have a significant effect on the chlorophyll (Chl) content and net photosynthetic rate (Pn) of the L40 Chinese cabbage compared with the L14 Chinese cabbage. These two different Chinese cabbage genotypes were shown to have differently expressed genes related to nitrate transport, auxin synthesis, and glutamate dehydrogenase synthesis. These genes function in the nitrogen pathway, which are important candidates for understanding the molecular host-response mechanisms to LN stress.

Genetic and Transcriptome Analysis of Leaf Trichome Development in Chinese Cabbage (Brassica rapa L. subsp. pekinensis) and Molecular Marker Development.

Chinese cabbage (Brassica rapa L. subsp. pekinensis) is one of the vegetables with the largest cultivated area in China and has been a great addition to the daily diet of Chinese people. A genetic map has been constructed in our previous study using the F2 population of two inbred lines of Chinese cabbage, namely "G291" (a hairy line) and "ZHB" (a hairless line), based on which a candidate gene related to trichome traits was identified on chromosome A06 with a phenotypic variance of 47%. A molecular marker was found to co-segregate with the trichome traits of the F2 population, which is in the 5'-flanking region of BrGL1, and a corresponding patent has been granted (NO. CN 108545775 B). Transcriptome analysis was carried out on the cotyledon, the first true leaf and the leaf closest to each inflorescence of F2 individuals of "G291 × ZHB" with or without trichomes, respectively. Ten pathways, including 189 DEGs, were identified to be involved in the development of trichomes in Chinese cabbage, which may be specifically related to the development of leaf trichomes. Most of the pathways were related to the biosynthesis of the secondary metabolites, which may help plants to adapt to the ever-changing external environment. DEGs also enriched the "plant-pathogen interaction" pathway, which is consistent with the conclusion that trichomes are related to the disease resistance of plants. Our study provides a basis for future research on the occurrence and development of trichomes in Chinese cabbage.

Enrichment-Detection Integrated Exosome Profiling Biosensors Promising for Early Diagnosis of Cancer.

Enrichment-detection integrated biosensors for exosome profiling have shown great potential in noninvasive diagnosis and point-of-care testing with the advantage of multifunctions. This Feature focuses on the enrichment-detection integrated exosome profiling biosensors emphasizing (i) the underlying working fundamentals of these sorts of biosensors, (ii) four advanced strategies developed for exosome analysis, and (iii) future outlook and present challenges of exosome profiling systems.

Attomolar-Level Ultrasensitive and Multiplex microRNA Detection Enabled by a Nanomaterial Locally Assembled Microfluidic Biochip for Cancer Diagnosis.

Non-invasive early diagnosis is of great significance in disease pathologic development and subsequent medical treatments, and microRNA (miRNA) detection has attracted critical attention in early cancer screening and diagnosis. High-throughput, sensitive, economic, and fast miRNA sensing platforms are necessary to realize the low-concentration miRNA detection in clinical diagnosis and biological studies. Here, we developed an attomolar-level ultrasensitive, rapid, and multiple-miRNA simultaneous detection platform enabled by nanomaterial locally assembled microfluidic biochips. This platform presents a large linear detection regime of 1 aM-10 nM, an ultralow detection limit of 0.146 aM with no amplification, a short detection time of 35 min with multiplex miRNA sensing capability, and a small sample volume consumption of 2 µL. The detection results of five miRNAs in real samples from breast cancer patients and healthy humans indicate its excellent capacity for practical applications in early cancer diagnosis. The proposed ultrasensitive, rapid, and multiple-miRNA detection microfluidic biochip platform is a universal miRNA detection approach and an important and valuable tool in early cancer screening and diagnosis as well as biological studies.

Mid-term outcomes of symptomatic isolated superior mesenteric artery dissection with endovascular management.

OBJECTIVES: The clinical outcomes, safety, and efficacy of endovascular management are explored for symptomatic isolated superior mesenteric artery dissection (ISMAD). METHODS: In this retrospective study, 51 consecutive patients with symptomatic ISMAD received endovascular management from three institutions between January 2011 and December 2019.These patients were categorized into group A (endovascular treatment was used as the first-line therapy) and group B(endovascular treatment was used as the second-line therapy). The general epidemiological data, clinical manifestations, first-episode symptoms, treatment process, imaging findings, follow-up outcomes were analyzed from the medical records. RESULTS: A total of 51 patients with endovascular management were collected in this study. Significant differences were observed between the two groups with respect to the course (150 h vs. 57 h; p < 0.001), intestinal ischemia (26.32% vs. 6,25%; p = 0.04) and dissection length (45.26 ± 13.78 mm vs. 63.37 ± 12.73 mm; p < 0.001). Technical success rate was 90.2% (46/51). There was significant difference in the MOD (42.27 ± 23.41 min vs. 76.63 ± 28.62 min p < 0.001), MPSRT (4.67 ± 2.65 h vs. 7.32 ± 2.49 h, p = 0.02), LOS (9.52 ± 3.72 days vs. 11.86 ± 4.13 days; p = 0.01) between the two groups. The bleeding complication rate was 7.84% (one patient in group A and three patients in group B). A total of 48 (94.12%, 48/51) patients were followed up for a median of 36.51 months (range, 4-87 months). Positive events of the SMA were achieved in 81.25% (39/48), and negative events of the SMA were achieved in 18.75% (8/48) based on the follow-up contrast-enhanced CT scan. CONCLUSIONS: Endovascular management of symptomatic ISMAD has a high technical success rate and efficient at controlling symptoms. Furthermore, as more positive events occur, endovascular management should be encouraged early when pain persists after conservative management or there are signs of disease progression.

A Clinical Prediction Model to Predict Heparin Treatment Outcomes and Provide Dosage Recommendations: Development and Validation Study.

BACKGROUND: Unfractionated heparin is widely used in the intensive care unit as an anticoagulant. However, weight-based heparin dosing has been shown to be suboptimal and may place patients at unnecessary risk during their intensive care unit stay. OBJECTIVE: In this study, we intended to develop and validate a machine learning-based model to predict heparin treatment outcomes and to provide dosage recommendations to clinicians. METHODS: A shallow neural network model was adopted in a retrospective cohort of patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database and patients admitted to the Peking Union Medical College Hospital (PUMCH). We modeled the subtherapeutic, normal, and supratherapeutic activated partial thromboplastin time (aPTT) as the outcomes of heparin treatment and used a group of clinical features for modeling. Our model classifies patients into 3 different therapeutic states. We tested the prediction ability of our model and evaluated its performance by using accuracy, the kappa coefficient, precision, recall, and the F1 score. Furthermore, a dosage recommendation module was designed and evaluated for clinical decision support. RESULTS: A total of 3607 patients selected from MIMIC III and 1549 patients admitted to the PUMCH who met our criteria were included in this study. The shallow neural network model showed results of F1 scores 0.887 (MIMIC III) and 0.925 (PUMCH). When compared with the actual dosage prescribed, our model recommended increasing the dosage for 72.2% (MIMIC III, 1240/1718) and 64.7% (PUMCH, 281/434) of the subtherapeutic patients and decreasing the dosage for 80.9% (MIMIC III, 504/623) and 76.7% (PUMCH, 277/361) of the supratherapeutic patients, suggesting that the recommendations can contribute to clinical improvements and that they may effectively reduce the time to optimal dosage in the clinical setting. CONCLUSIONS: The evaluation of our model for predicting heparin treatment outcomes demonstrated that the developed model is potentially applicable for reducing the misdosage of heparin and for providing appropriate decision recommendations to clinicians.

Ultrasensitive, high-throughput, and rapid simultaneous detection of SARS-CoV-2 antigens and IgG/IgM antibodies within 10 min through an immunoassay biochip.

COVID-19 is now a severe threat to global health. Facing this pandemic, we developed a space-encoding microfluidic biochip for high-throughput, rapid, sensitive, simultaneous quantitative detection of SARS-CoV-2 antigen proteins and IgG/IgM antibodies in serum. The proposed immunoassay biochip integrates the advantages of graphene oxide quantum dots (GOQDs) and microfluidic chip and is capable of conducting multiple SARS-CoV-2 antigens or IgG/IgM antibodies of 60 serum samples simultaneously with only 2 µL sample volume of each patient. Fluorescence intensity of antigens and IgG antibody detection at emission wavelength of ~680 nm was used to quantify the target concentration at excitation wavelength of 632 nm, and emission wavelength of ~519 nm was used during the detection of IgM antibodies at excitation wavelength of 488 nm. The method developed has a large linear quantification detection regime of 5 orders of magnitude, an ultralow detection limit of ~0.3 pg/mL under optimized conditions, and less than 10-min qualitative detection time. The proposed biosensing platform will not only greatly facilitate the rapid diagnosis of COVID-19 patients, but also provide a valuable screening approach for infected patients, medical therapy, and vaccine recipients.

The Effect of Functional Fiber on Microbiota Composition in Different Intestinal Segments of Obese Mice.

The gastrointestinal tract is a heterogeneous ecosystem with distinct, stratified environments, which leads to different microbial composition in different intestinal segments. The regional heterogeneity of intestinal microbiota complicates the relationship between diet and microbiota. Few studies have focused on the effects of different diets on microbiota in different intestinal segments. This study aimed to investigate the effects of functional fiber on the microbial composition in multiple intestinal segments from a high-fat diet compared with a normal chow diet. We found that the response of microbiota from different intestinal segments to diet was related to the intestinal physiologic function and the physicochemical properties of dietary nutrients. A high-fat diet drove changes in the microbial composition in the hindgut, possibly by affecting the digestive environment of the foregut, and increased the regional heterogeneity of the whole intestinal microbiota. The supplementation of functional fiber promoted the microbial transfer and colonization from the anterior to the posterior intestinal segments, and increased the regional similarity of intestinal microbiota accordingly, particularly within the hindgut. The gut fermentation of the functional fiber, which mainly occurred in the hindgut, resulted in a significant change in the microbial composition and metabolism in the cecum and colon, with richer carbohydrate metabolism-related bacteria, including Mucispirillum, Prevotella, Anaerostipes, Oscillospira, Ruminococcus, Bacteroides, Coprococcus, Ruminococcus (Lachnospiraceae), and Allobaculum, and higher production of acetate and butyrate. We concluded that multiple regulatory mechanisms of diets which affect microbiota composition exist, including microbial metabolism, microbial migration, and the regulation of the intestinal environment.

Ultrasensitive Detection of COVID-19 Causative Virus (SARS-CoV-2) Spike Protein Using Laser Induced Graphene Field-Effect Transistor.

COVID-19 is a highly contagious human infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the war with the virus is still underway. Since no specific drugs have been made available yet and there is an imbalance between supply and demand for vaccines, early diagnosis and isolation are essential to control the outbreak. Current nucleic acid testing methods require high sample quality and laboratory conditions, which cannot meet flexible applications. Here, we report a laser-induced graphene field-effect transistor (LIG-FET) for detecting SARS-CoV-2. The FET was manufactured by different reduction degree LIG, with an oyster reef-like porous graphene channel to enrich the binding point between the virus protein and sensing area. After immobilizing specific antibodies in the channel, the FET can detect the SARS-CoV-2 spike protein in 15 min at a concentration of 1 pg/mL in phosphate-buffered saline (PBS) and 1 ng/mL in human serum. In addition, the sensor shows great specificity to the spike protein of SARS-CoV-2. Our sensors can realize fast production for COVID-19 rapid testing, as each LIG-FET can be fabricated by a laser platform in seconds. It is the first time that LIG has realized a virus sensing FET without any sample pretreatment or labeling, which paves the way for low-cost and rapid detection of COVID-19.

Mitochondrial Pyruvate Carriers Prevent Cadmium Toxicity by Sustaining the TCA Cycle and Glutathione Synthesis.

Cadmium (Cd) is a major heavy metal pollutant, and Cd toxicity is a serious cause of abiotic stress in the environment. Plants protect themselves against Cd stress through a variety of pathways. In a recent study, we found that mitochondrial pyruvate carriers (MPCs) are involved in Cd tolerance in Arabidopsis (Arabidopsis thaliana). Following the identification of MPCs in yeast (Saccharomyces cerevisiae) in 2012, most studies have focused on the function of MPCs in animals, as a possible approach to reduce the risk of cancer developing. The results of this study show that AtMPC protein complexes are required for Cd tolerance and prevention of Cd accumulation in Arabidopsis. AtMPC complexes are composed of two elements, AtMPC1 and AtMPC2 (AtNRGA1 or AtMPC3). When the formation of AtMPCs was interrupted by the loss of AtMPC1, glutamate could supplement the synthesis of acetyl-coenzyme A and sustain the TCA cycle. With the up-regulation of glutathione synthesis following exposure to Cd stress, the supplementary pathway could not efficiently drive the tricarboxylic acid cycle without AtMPC. The ATP content decreased concomitantly with the deletion of tricarboxylic acid activity, which led to Cd accumulation in Arabidopsis. More importantly, ScMPCs were also required for Cd tolerance in yeast. Our results suggest that the mechanism of Cd tolerance may be similar in other species.

Multi-GPU Based Parallel Design of the Ant Colony Optimization Algorithm for Endmember Extraction from Hyperspectral Images.

Spectral unmixing is a vital procedure in hyperspectral remote sensing image exploitation. The linear mixture model has been widely utilized to unmix hyperspectral images by extracting a set of pure spectral signatures, called endmembers in hyperspectral jargon, and estimating their respective fractional abundances in each pixel of the scene. Many algorithms have been proposed to extract endmembers automatically, which is a critical step in the spectral unmixing chain. In recent years, the ant colony optimization (ACO) algorithm has been developed for endmember extraction from hyperspectral data, which was regarded as a combinatorial optimization problem. Although the ACO for endmember extraction (ACOEE) can acquire accurate endmember results, its high computational complexity has limited its application in the hyperspectral data analysis. The GPUs parallel computing technique can be utilized to improve the computational performance of ACOEE, but the architecture of GPUs determines that the ACOEE should be redesigned to take full advantage of computing resources on GPUs. In this paper, a multiple sub-ant-colony-based parallel design of ACOEE was proposed, in which an innovative mechanism of local pheromone for sub-ant-colonies is utilized to enable ACOEE to be preferably executed on the multi-GPU system. The proposed method can avoid much synchronization among different GPUs to affect the computational performance improvement. The experiments on two real hyperspectral datasets demonstrated that the computational performance of ACOEE significantly benefited from the proposed methods.

Overexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma.

This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma. GGPPS expression was detected in lung adenocarcinoma tissues by qRT-PCR, tissue microarray (TMA) and western blotting. The relationships between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients were assessed. GGPPS was down-regulated in SPCA-1, PC9 and A549 cells using siRNA and up-regulated in A549 cells using an adenoviral vector. The biological roles of GGPPS in cell proliferation, apoptosis, migration and invasion were determined by MTT and colony formation assays, flow cytometry, and transwell and wound-healing assays, respectively. In addition, the regulatory roles of GGPPS on the expression of several epithelial-mesenchymal transition (EMT) markers were determined. Furthermore, the Rac1/Cdc42 prenylation was detected after knockdown of GGPPS in SPCA-1 and PC9 cells. GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of GGPPS was correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients. Knockdown of GGPPS inhibited the migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E-cadherin and reduced the expression of N-cadherin and vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42 geranylgeranylation was reduced by GGPPS knockdown. Overexpression of GGPPS correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating EMT.

Expression profiles and clinical value of plasma exosomal Tim-3 and Galectin-9 in non-small cell lung cancer.

Exosomes are membrane-bound, virus-sized vesicles present in circulating blood. Tumor cells are avid producers of exosomes, which are thought to mimic molecular features of parent tumor cells. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) is a the next-generation immune checkpoint that can be activated by its ligand Galectin-9 to negatively regulate the anti-tumor immune response. However, the characteristics of plasma exosomal Tim-3 and Galectin-9 (Exo-T/G) in cancer remained unknown. This study was conducted to investigate the expression patterns and clinical value of plasma exosomal total protein (Exo-pro) and Exo-T/G in non-small cell lung cancer (NSCLC). Plasma was collected from 103 NSCLC patients including 60 early stages and 43 advanced stages disease samples as well as 56 healthy subjects. Exosomes were isolated from plasma by commercial exosome precipitation solution and identified by western blotting of CD63 and transmission electron microscopy. Exo-pro concentration was measured by the BCA assay. Enzyme-linked immunosorbent assay was used to quantify Exo-T/G. Additionally, 34 NSCLC samples were applied to directly detect plasma TIM-3 (Plas-T) and Galectin-9 (Plas-G). Our results showed that Exo-pro, Exo-T, and Exo-G were significantly increased in NSCLC plasma compared to that in the healthy samples. High levels of Exo-T and Exo-G were all positively correlated with several malignant parameters, including larger tumor size, advanced stages, and more distant metastasis. High levels of Exo-pro and Exo-T were also correlated with more lymph node metastasis. Additionally, plasma from lung squamous cell carcinoma showed higher Exo-T and Exo-G compared with that from lung adenocarcinoma. ALK-positive patients showed to have decreased Exo-T and Exo-G levels. Pearson's correlation analysis revealed a significant correlation between Exo-pro and Exo-T/G, Exo-T and Exo-G, Exo-T and Plas-T, Exo-G and Plas-G, and Plas-T and Plas-G. Together, our data revealed that Exo-pro, especially Exo-T and Exo-G could be potential biomarkers for NSCLC. Further studies focusing on pure tumor-derived exosomes isolated from plasma were needed.

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.