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Retinal microaneurysm (MA) is a definite earliest clinical sigh of diabetic retinopathy (DR). Its automatic segmentation is key to realizing intelligent screening for early DR, which can significantly reduce the risk of visual impairment in patients. However, the minute scale and subtle contrast of MAs against the background pose challenges for segmentation. This paper focuses on automatic MA segmentation in fundus images. A novel pyramid feature fusion network (PFFNet) that progressively develops and fuses rich contextual information by integrating two pyramid modules is proposed. Multiple global pyramid scene parsing (GPSP) modules are introduced between the encoder and decoder to provide diverse global contextual information for the decoder through reconstructing skip connections. Additionally, a spatial scale‐aware pyramid (SSAP) module is introduced to dynamically fuse multi‐scale contextual information. This rich contextual information will help to identify MAs from low‐contrast background. Furthermore, to mitigate issue related to category imbalance, a combo loss function is introduced. Finally, to validate the effectiveness of the proposed method, experiments are conducted on two publicly available datasets, IDRiD and DDR, and PFFNet is compared with several state‐of‐the‐art models. The experimental results demonstrate the superiority of our PFFNet in the MA segmentation task. [ABSTRACT FROM AUTHOR]

This work takes the natural gas hydrate (NGH) reservoir in the Shenhu area at the South China Sea as the target. Using the quartz sand, calcite grains, and illite powder as the main mineral composites, and Portland cement as the bonding material, the host skeleton with similar porosity and mechanical properties to the target reservoir were prepared. Ice was used to simulate natural gas hydrates for their high similarity in mechanical properties and distributions within porous host. The ice saturation in the host skeleton is quantitatively controlled by the quality method. As an analogical simulation, artificial samples with different ice saturations were tested by uniaxial compression measurements and the Brazilian tensile tests, aiming to reveal the mechanical behavior of NGH sediments. The results indicated that the plasticity of the artificial sample increases and its damage form transitions from brittleness to ductility as the ice saturation increases. The effects of free water and ice on the strength of saturated samples are quite different. The free water tends to reduce the strength of the sample due to illite hydration and change of internal friction. The bonding effect of ice tends to increase the strength of the sample, while the ice could also reduce the internal friction. When the ice saturation is larger than 30%, the compressive and tensile strengths of the sample increase with ice saturation, which could be regressed as yc = 2.2628S + 0.8322, and yt = 0.411S + 0.0273, respectively. The constitutive model was developed based on the equivalent medium theory and the D‐P criterion, which could describe the experiment data well with deviations less than 10%. [ABSTRACT FROM AUTHOR]

Collaborative conversion of methane and carbon dioxide into sustainable chemicals is an appealing solution to simultaneously overcome both environmental problems and energy crisis. However, this reaction is limited to the preparation of syngas with the unfavorable feature for transportation and storage. Herein, liquid formaldehyde as product is fabricated by the collaborative conversion of methane and carbon dioxide using anatase phase titanium dioxide as photocatalyst. The productivity reaches 14.65 mmol g−1 with 88.32% selectivity. In situ diffuse reflectance Fourier transform infrared spectroscopy, isotope testes, and theoretical calculation clarify that the photoexcited holes and electrons engage into methane oxidation and carbon dioxide reduction over anatase using surface hydroxyl species and oxygen vacancy as active sites, respectively. The consumption of surface hydroxyl species on methane oxidation promotes the oxygen vacancy formation for carbon dioxide adsorption, mutually the carbon dioxide provides the oxygen atom for surface hydroxyl species facilitating methane oxidation. The consumption of photoelectrons and photoholes on carbon dioxide reduction and methane oxidation balances the number of photogenerated carriers and ensures the catalytic system stability. In this work, the avenue is broadened toward the co‐conversion of greenhouse gas into desirable chemical products in a sustainable way. [ABSTRACT FROM AUTHOR]

Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Redundancy elimination techniques are extensively investigated to reduce storage overheads for cloud‐assisted health systems. Deduplication eliminates the redundancy of duplicate blocks by storing one physical instance referenced by multiple duplicates. Delta compression is usually regarded as a complementary technique to deduplication to further remove the redundancy of similar blocks, but our observations indicate that this is disobedient when data have sparse duplicate blocks. In addition, there are many overlapped deltas in the resemblance detection process of post‐deduplication delta compression, which hinders the efficiency of delta compression and the index phase of resemblance detection inquires abundant non‐similar blocks, resulting in inefficient system throughput. Therefore, a multi‐feature‐based redundancy elimination scheme, called MFRE, is proposed to solve these problems. The similarity feature and temporal locality feature are excavated to assist redundancy elimination where the similarity feature well expresses the duplicate attribute. Then, similarity‐based dynamic post‐deduplication delta compression and temporal locality‐based dynamic delta compression discover more similar base blocks to minimise overlapped deltas and improve compression ratios. Moreover, the clustering method based on block‐relationship and the feature index strategy based on bloom filters reduce IO overheads and improve system throughput. Experiments demonstrate that the proposed method, compared to the state‐of‐the‐art method, improves the compression ratio and system throughput by 9.68% and 50%, respectively. [ABSTRACT FROM AUTHOR]

This study aimed to identify genes shared by metabolic dysfunction‐associated fatty liver disease (MASH) and diabetic nephropathy (DN) and the effect of extracellular matrix (ECM) receptor interaction genes on them. Datasets with MASH and DN were downloaded from the Gene Expression Omnibus (GEO) database. Pearson's coefficients assessed the correlation between ECM‐receptor interaction genes and cross talk genes. The coexpression network of co‐expression pairs (CP) genes was integrated with its protein–protein interaction (PPI) network, and machine learning was employed to identify essential disease‐representing genes. Finally, immuno‐penetration analysis was performed on the MASH and DN gene datasets using the CIBERSORT algorithm to evaluate the plausibility of these genes in diseases. We found 19 key CP genes. Fos proto‐oncogene (FOS), belonging to the IL‐17 signalling pathway, showed greater centrality PPI network; Hyaluronan Mediated Motility Receptor (HMMR), belonging to ECM‐receptor interaction genes, showed most critical in the co‐expression network map of 19 CP genes; Forkhead Box C1 (FOXC1), like FOS, showed a high ability to predict disease in XGBoost analysis. Further immune infiltration showed a clear positive correlation between FOS/FOXC1 and mast cells that secrete IL‐17 during inflammation. Combining the results of previous studies, we suggest a FOS/FOXC1/HMMR regulatory axis in MASH and DN may be associated with mast cells in the acting IL‐17 signalling pathway. Extracellular HMMR may regulate the IL‐17 pathway represented by FOS through the Mitogen‐Activated Protein Kinase 1 (ERK) or PI3K‐Akt–mTOR pathway. HMMR may serve as a signalling carrier between MASH and DN and could be targeted for therapeutic development. [ABSTRACT FROM AUTHOR]

The effective conversion of carbon dioxide (CO2) and nitrogen (N2) into urea by photocatalytic reaction under mild conditions is considered to be a more environmentally friendly and promising alternative strategies. However, the weak adsorption and activation ability of inert gas on photocatalysts has become the main challenge that hinder the advancement of this technique. Herein, we have successfully established mesoporous CeO2‐x nanorods with adjustable oxygen vacancy concentration by heat treatment in Ar/H2 (90 % : 10 %) atmosphere, enhancing the targeted adsorption and activation of N2 and CO2 by introducing oxygen vacancies. Particularly, CeO2‐500 (CeO2 nanorods heated treatment at 500 °C) revealed high photocatalytic activity toward the C−N coupling reaction for urea synthesis with a remarkable urea yield rate of 15.5 μg/h. Besides, both aberration corrected transmission electron microscopy (AC‐TEM) and Fourier transform infrared (FT‐IR) spectroscopy were used to research the atomic surface structure of CeO2‐500 at high resolution and to monitor the key intermediate precursors generated. The reaction mechanism of photocatalytic C−N coupling was studied in detail by combining Density Functional Theory (DFT) with specific experiments. We hope this work provides important inspiration and guiding significance towards highly efficient photocatalytic synthesis of urea. [ABSTRACT FROM AUTHOR]

Lung cancer is an incurable disease with an increased mortality rate caused by the inhalation of dust‐containing crystalline silica particles. Silica exposure is one of the most important occupational hazards in the world. Whether the association between silica exposure and lung cancer is because of the fibrotic process or to the effect of respirable silica itself is unclear. The International Agency for Research on Cancer (IARC) classified silica as a human lung carcinogen. The opinion of lung cancer is a question that has been addressed in this review. Three electronic databases, including MEDLINE, Scopus, and Web of Science, were used to search for relevant literature from 2000 to 2022. To evaluate the relationship between exposure to silica and developing lung cancer, we performed a meta‐analysis using the random‐effects model. For each study, the overall odds ratio (OR), relative risk (RR) with 95% confidence intervals (CI), and p values were calculated. An extensive database search resulted in the selection of 20 (case‒control and nested case‒control studies were selected) out of 527 studies. Among the 20 selected studies, 7 studies showed a significant association between silica exposure and an increased risk of lung cancer. Further analysis showed that among the selected studies, six studies showed a significant correlation between combined exposure to silica and smoking with an increased risk of lung cancer. The data from the present study showed that smoking habits increased the impact of silica exposure on the initiation of lung carcinogenesis in exposed workers. [ABSTRACT FROM AUTHOR]

Summary: With the number of services expanding in the Internet of Things (IoT), the limited resources of user terminals are insufficient to satisfy the computation needs of all running services. Therefore, we design a collaborative computation‐offloading model (CCOM) composed of multiple servers and task offloading modes to solve the problem by offloading tasks from resource‐constrained terminals to other computing entities, which achieves the following four objectives: model execution time minimization, task execution time minimization, energy consumption minimization, and most efficient device workload. And the global evaluation strategy based on angle and distance is proposed to address the individual selection problems caused by the overly localized Pareto dominance relationship and objective conflicts in the many‐objective evolutionary algorithms. In simulations, the strategy achieves the best Inverted Generation Distance (IGD) performance on 22 benchmark test problems based on Wilcoxon's rank sum statistical test and improves performance in the four objectives above by 18%, 31%, 20%, and 42%, respectively. Finally, we think that the strategy can provide adequate offloading performance for decision‐makers. [ABSTRACT FROM AUTHOR]

Pyrrolizidine alkaloids (PAs) constitute a class of phytotoxin which demonstrates strong hepatotoxicity. In China, many plants containing PAs are used as traditional medicines or medicinal preparations, which could harm human health and safety. Xiaoyao Tablet (XYT) is an antidepressant drug registered in the European Union (EU), Compound Danshen Dropping Pills (CDDP) is a commonly used drug for coronary heart disease, and phase III clinical study is ongoing in the United States. The purpose of this study is to provide data to support the use of Chinese medicine preparations internationally and to establish analytical methods for 32 PAs in XYT and CDDP. The extraction parameters that were optimized include solid-phase extraction (SPE) cartridge, extraction method, and extraction solvent. Then ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-traptandem mass spectrometry (UPLC-MS/MS) was developed to effectively and efficiently quantify the 32 PAs of the XYT and CDDP. The analytical methods for XYT and CDDP were verified respectively. For XYT, the analytical method for 32 PAs was linear, and the correlation coefficient r was greater than 0.994; the recovery (REC%) at 10–2000 μg/kg was 73.3%–118.5%, and the relative standard deviation (RSD%) was 2.1%–15.4%. The CDDP REC% was 71.8%–112.0%, and the RSD% was 2.0%–17.1%. This study provides technical and data support for the registration of Chinese patented medicines in the EU, controls quality and ensures safety, and is committed to the internationalization and standardization of Chinese patented medicines. [ABSTRACT FROM AUTHOR]

This paper addresses the adaptive control problem for a one‐link manipulator system driven by a motor with uncertain virtual control coefficients (VCCs) and nonlinearities. The unknown VCCs are composed by the certain and uncertain items, where the first part is decided by the moment of inertia of the manipulator and another is generated by that of the load. An auxiliary variable and the Nussbaum gain technique are invoked to handle the uncertainties of VCCs and input nonlinearities. Moreover, a finite‐time prescribed performance function is introduced to design the adaptive control scheme for the manipulator system, which guarantees the tracking error converges to a fixed interval in a setting time and all signals in the manipulator system are bounded. [ABSTRACT FROM AUTHOR]

Purpose. To investigate infection risk factors after secondary internal fixation (IF) of open fracture of a long bone with removed fixation frame and explore the safe range of feasible operation for abnormal inflammatory indicators. Methods. Clinical data of 117 cases of open fracture of a long bone that underwent temporary external fixation (EF) in one stage and IF in two stages were retrospectively analyzed. Collected data included age, sex, Gustilo type, multiple injuries, debridement time, duration of EF, needle infection, interval of conversion to IF after external fixator, preoperative white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin (ALB), blood glucose, and prognosis. We selected these factors for univariate analysis of postoperative surgical site infection (SSI) and multivariate logistic regression analysis of statistically significant risk factors and created receiver operating characteristic (ROC) curves to compare the diagnostic efficiency of each index and determine the optimal screening point. Results. We followed up 117 patients, with 130 limbs affected. Univariate analysis showed that ESR, CRP, ALB, WBC, EF time, and Gustilo fracture type were significantly associated with SSI. Multivariate logistic regression analysis showed that CRP, duration of EF, and Gustilo fracture type were independently associated with postoperative infection. Area under ROC curves for WBC, ESR, and CRP were 69.7%, 73.2%, and 81.2%. Conclusions. We demonstrated the role of Gustilo classification of open fractures in predicting postoperative infection, especially for open fractures above type III. If the inflammatory indexes return to normal or show a downward trend, and the second-stage IF operation is performed within the cutoff values, postoperative recurrent infection was reduced. [ABSTRACT FROM AUTHOR]

An efficient hydrazine substitution of p‐nitro‐aryl fluorides with hydrazine hydrates catalyzed by FeO(OH)@C nanoparticles is described. This hydrazine substitutions of p‐nitro‐aryl fluorides bearing electron‐withdrawing groups proceeded efficiently with high yield and selectivity. Similarly, hydrogenations of p‐nitro‐aryl fluorides containing electron‐donating groups also smoothly proceeded under mild conditions. Furthermore, with these prepared aryl hydrazines, some phthalazinones, interesting as potential structures for pharmaceuticals, have successfully been synthesized in high yields. [ABSTRACT FROM AUTHOR]

Sodium aluminate (NaAlO2) can be used to accelerate hydration of Portland cements. Here, we compare the use of NaAlO2 solutions with deionized water on the hydration of Al‐doped β‐C2S. The microstructure development of hydration product C‐S‐H obtained from hydrated Al‐doped β‐C2S was investigated. NaAlO2 significantly improved the hydration kinetics of Al‐doped β‐C2S due to the enhancement in the precipitation of calcium hydroxide and stimulation of C‐(A)‐S‐H nucleation and increased the early‐age mechanical strength of Al‐doped β‐C2S pastes. NaAlO2 promoted the incorporation of Al in the C‐(A)‐S‐H structure and accelerated the formation of C‐(A)‐S‐H phases containing tetra‐, penta‐ and hexa‐coordinated Al in its composition. The alkali cations modified the electrostatic equilibrium of the C‐(A)‐S‐H, thus promoting the development of the nano‐mechanical properties. [ABSTRACT FROM AUTHOR]

Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor and inhibits cholesterol synthesis. Recently, atorvastatin also showed anti-inflammatory effect in acute lung injury, ameliorating pulmonary gas-blood exchanging function. Sphingosine kinase 1 plays a central role in endothelial (EC) cytoskeleton rearrangement and EC barrier integrity regulation. In this study, the role of sphingosine kinase 1 in atorvastatin anti-inflammatory effect against acute lung injury was investigated. Both wild-type (WT) and SphK1-/- mice were challenged with high tidal volume ventilation (40 ml/kg body weight, 65 breathing/min, 4 hours). The acute lung injury was evaluated and the mechanisms were explored. In WT mice, atorvastatin treatment significantly decreased acute lung injury responding to high tidal volume ventilation (HT), including protein, cellular infiltration, and cytokine releasing; comparing to WT mice, SphK1-/- mice showed significantly worsen pulmonary injuries on HT model. Moreover, the atorvastatin-mediated anti-inflammatory effect was diminished in SphK1-/- mice. To further confirm the role of SphK1 in VILI, we then compared the inflammatory response of endothelial cells that were isolated from WT and SphK1-/- mice to cyclic stretching. Similarly, atorvastatin significantly decreased cytokine generation from WT EC responding to cyclic stretching. Atorvastatin also significantly preserved endothelial junction integrity in WT EC against thrombin challenge. However, the inhibitory effect of atorvastatin on cytokine generation induced by cyclic stretching was abolished on SphK1-/- mice EC. The endothelial junction integrity effects of atorvastatin also diminished on SphK1-/- mouse EC. Signal analysis indicated that atorvastatin inhibited JNK activation induced by cyclic stretch. SphK1 knockout also blocked atorvastatin-mediated VE-cadherin junction enhancement. In summary, by inhibition of MAPK activity and maintenance of EC junction homeostasis, SphK1 plays a critical role in atorvastatin-mediated anti-inflammatory effects in both cellular and in vivo model. This study also offers an insight into mechanical stress-mediated acute lung injury and potential therapy in the future. [ABSTRACT FROM AUTHOR]

QXOH‐LB, a fixed‐dose combination (35 mM QXOH and 10 mM levobupivacaine) has been shown to induce a long duration of local anesthesia in animal efficacy testing, which indicates potential for postoperative pain management. In this study, we evaluated the potential toxicity of QXOH‐LB in NIH mice under the Guidance on the repeated‐dose toxicity published by the China Food and Drug Administration. Mice (n = 30 per sex per group) were subcutaneously injected 5, 10, 20 mg/kg QXOH‐LB, 5, 10, 20 mg/kg QXOH, and 5 mg/kg levobupivacaine (LB) once a day for 14 days with sacrifice of main study animals; remaining mice (n = 10 per sex per group) were monitored for an additional 4‐week recovery period. Mice in the 10 and 20 mg/kg QXOH, and 20 mg/kg QXOH‐LB died, which was considered due to excessive respiratory inhibition. The doses of 10 mg/kg QXOH‐LB and 5 mg/kg QXOH were well tolerated without any clinical signs of toxicity. Therefore, the no‐observed‐adverse‐effect level (NOAEL) of QXOH‐LB and QXOH was considered to be 10 and 5 mg/kg/day, respectively. In the dose range from 5 to 20 mg/kg, the exposure of QXOH and LB in QXOH‐LB was equal to each agent used alone at the same dose in NIH mice. There was no gender difference on exposure and no evidence of accumulation. In 14‐day repeated dosing study, mice in the 10 and 20 mg/kg QXOH, and 20 mg/kg QXOH‐LB died, which was considered due to excessive respiratory inhibition. The NOAEL of QXOH‐LB and QXOH was 10 and 5 mg/kg/day, respectively. The exposure of QXOH and LB in QXOH‐LB was equal to each agent used alone at the same dose in NIH mice, and there was no gender difference on exposure and no evidence of accumulation. [ABSTRACT FROM AUTHOR]

The fault diagnosis approaches based on k -nearest neighbor rule have been widely researched for industrial processes and achieve excellent performance. However, for quality-related fault diagnosis, the approaches using k -nearest neighbor rule have been still not sufficiently studied. To tackle this problem, in this article, we propose a novel quality-related fault diagnosis framework, which is made up of two parts: fault detection and fault isolation. In the fault detection stage, we innovatively propose a novel non-linear quality-related fault detection method called kernel partial least squares- k -nearest neighbor rule, which organically incorporates k -nearest neighbor rule with kernel partial least squares. Specifically, we first employ kernel partial least squares to establish a non-linear regression model between quality variables and process variables. After that, the statistics and thresholds corresponding to process space and predicted quality space are appropriately designed by adopting k -nearest neighbor rule. In the fault isolation stage, in order to match our proposed non-linear quality-related fault detection method kernel partial least squares- k -nearest neighbor seamlessly, we propose a modified variable contributions by k -nearest neighbor (VCkNN) fault isolation method called modified variable contributions by k -nearest neighbor (MVCkNN), which elaborately introduces the idea of the accumulative relative contribution rate into VC k -nearest neighbor, such that the smearing effect caused by the normal distribution hypothesis of VC k -nearest neighbor can be mitigated effectively. Finally, a widely used numerical example and the Tennessee Eastman process are employed to verify the effectiveness of our proposed approach. [ABSTRACT FROM AUTHOR]

QXOH‐Levobupivacaine (LB) is a fixed‐dose combination of 35‐mM QXOH and 10‐mM LB. It was developed for perioperative analgesia because of its long‐acting analgesic effect. The purpose of this study was to evaluate the potential toxicity of QXOH‐LB in beagle dogs in accordance with the Guidance on the repeated‐dose toxicity published by the China Food and Drug Administration. Groups of five male and five female beagle dogs received normal saline, QXOH‐LB (2, 4, and 8 mg/kg, calculated as QXOH), QXOH (2, 4, and 8 mg/kg), or LB (2 mg/kg, equals the concentration of LB in 8‐mg/kg QXOH‐LB group) at the volume of 1 mL/kg once per day for 14 days through subcutaneous injection. No mortality was observed. Dogs in the control group as well as animals treated with 2‐mg/kg QXOH or QXOH‐LB exhibited normal behaviors. Clinical signs of toxicity in dogs treated with 4 and 8 mg/kg of QXOH or QXOH‐LB included decreased activity, unsteady gait, jerks, tremors, vocalization, emesis, ataxia, lateral/sternal recumbency, deep/rapid respiration, and gasping. Additionally, neurological function was found to be affected by QXOH and QXOH‐LB at the doses of 4 and 8 mg/kg. All clinical signs were recovered within 24 h. The no‐observed‐adverse‐effect level of QXOH and QXOH‐LB was considered to be 2 mg/kg. Toxicokinetic data showed that exposure to QXOH and LB increased as QXOH‐LB doses were increased from 4 to 8 mg/kg. There was no evidence of drug accumulation or any effect of gender. In our 14‐day repeated‐dose study, no dog mortality was observed. Toxicity‐related clinical signs and neurological function interference were observed in beagle dogs treated with 4 and 8 mg/kg of QXOH or QXOH‐LB. The no‐observed‐adverse‐effect level for QXOH and QXOH‐LB was considered to be 2 mg/kg. Toxicokinetic data showed that exposure to QXOH and LB increased as QXOH‐LB doses were increased from 4 to 8 mg/kg. There was no evidence of drug accumulation or any effect of gender. [ABSTRACT FROM AUTHOR]

ET‐26 hydrochloride (ET‐26HCl), a novel analog of etomidate, induces as effective sedation, with good cardiac and respiratory stability, as etomidate but with mild adrenocortical suppression. The objective of this study was to evaluate the potential adverse effects of ET‐26HCl in rats. In a single‐dose toxicity study, abnormal urine color (red) was observed in all groups: control (100%), 8 mg/kg (10%), 16 mg/kg (50%), and 20 mg/kg (70%) ET‐26HCl, which returned to normal on the day of dosing. There were no mortalities or serious toxicological signs; the maximum tolerable dose of ET‐26HCl was 20 mg/kg. In the repeated‐dose toxicity study, deaths occurred in the 12‐ (13.33% of males) and 16‐mg/kg/day (20% of males and 3.33% of females) groups. Abnormal urine color (red or brown) was detected in the control group (10%) and all treatment groups (30%, 46.67%, and 40% at 8, 12 and 16 mg/kg/day, respectively), at a frequency of 1.43% in the control group, 4.76% in 8 mg/kg/day, 7.62% in 12 mg/kg/day, and 4.29% in 16 mg/kg/day. Increases in neutrophils and plasma fibrinogen were temporary and recoverable effects. Macroscopic and histopathologic changes were found only at the injection sites: abnormal skin color, scabbing, thrombus, ulceration, and inflammation. During the recovery period, there was evidence of reversibility, including fibroblast proliferation and vessel recanalization. The no‐observed‐adverse‐effect level of ET‐26HCl was 8 mg/kg/day. Toxicokinetic variables of ET‐26HCl, except the calculated initial concentration in females on Day 1, showed a dose‐dependent increase to exposure, with no gender difference and no evidence of accumulation. In the single‐dose toxicity study, there were no mortalities or serious toxicological signs; the maximum tolerable dose of ET‐26HCl was 20 mg/kg. In the repeated‐dose toxicity study, deaths occurred in the 12‐ and 16‐mg/kg/day groups. Toxicokinetic variables of ET‐26HCl, except the calculated initial concentration in females on Day 1, showed a dose‐dependent increase to exposure, with no gender difference and no evidence of accumulation. The no‐observed‐adverse‐effect level of ET‐26HCl was 8 mg/kg/day. [ABSTRACT FROM AUTHOR]

Background: The present study with trial sequential analysis (TSA) was conducted to evaluate comprehensively the efficacy and safety of dexmedetomidine and midazolam in pediatric sedation, and to investigate whether the outcomes achieved the required information size to draw the conclusions. Methods: PubMed, Embase, and Cochrane Library were searched from inception to October 2019. All randomized controlled trials used dexmedetomidine and midazolam in pediatric sedation were enrolled. Sedative efficacy, postoperative analgesic effect, and incidence of emergence agitation were considered as the co‐primary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to rate the quality of evidences. Results: We acquired data from 34 studies involving 2281 pediatric patients. The results indicated that administration of dexmedetomidine was associated with less incidence of emergence agitation (RR = 0.78, with 95% CI [0.65, 0.92]) and more satisfactory sedation at parental separation (RR = 0.31, with 95% CI [0.24, 0.41]) compared to midazolam, and the current sample sizes were sufficient with unnecessary further trials. Two groups did not differ significantly in sedation level at mask induction (RR = 0.86, with 95% CI [0.74, 1.00]). And using of dexmedetomidine was associated with less incidence of postoperative analgesic rescue (RR = 0.57, with 95% CI [0.35, 0.93]), but the number of patients was too few to achieve the required information size and to draw reliable conclusions. Premedication of dexmedetomidine was associated with significant less value of SBP, heart rate, increased incidence of bradycardia, and a lower rate of shivering. And there were no differences about onset of sedation and recovery time between two groups. Conclusions: Given that more satisfactory sedation at separation from parents and less incidence of emergence agitation, dexmedetomidine is preferred for pediatric sedation. However, compared with midazolam, the superiority of dexmedetomidine in providing adequate sedation at mask induction and postoperative analgesic effects has not yet been defined. [ABSTRACT FROM AUTHOR]

ET‐26 hydrochloride (ET‐26HCl) is a novel etomidate analogue, approved for clinical trials, which has an effective sedative‐hypnotic effect, a stable myocardial performance, and milder adrenocortical suppression than etomidate in rats and beagle dogs. Additionally, ET‐26HCl showed similar hemodynamic stability as etomidate in the rat uncontrolled hemorrhagic shock model. Furthermore, ET‐26HCl, in the rat lipopolysaccharide‐induced sepsis model, was found to have a higher survival rate, a lower inflammatory reaction, and less organ injury. In the present study, we measured the potential adverse effects of ET‐26HCl in beagle dogs in accordance with the Guidance on single‐ and repeated‐dose toxicity published by the China Food and Drug Administration. In toxicity studies, single and repeated (14 days) intravenous doses of up to 16 mg/kg were well tolerated, with only pharmacologically related clinical signs seen in both studies. Thus, the no‐observed‐adverse‐effect level (NOAEL) of ET‐26HCl was found at 16 mg/kg/day. Toxicokinetic examination demonstrated that ET‐26HCl showed a dose‐dependent increase to exposure, no gender difference, and no evidence of accumulation. These results provide useful information for guiding a phase I clinical trial of ET‐26HCl in healthy volunteers. ET‐26 hydrochloride is a novel intravenous anesthetic that has an effective sedative‐hypnotic effect, a stable myocardial performance, and milder adrenocortical suppression than etomidate. In toxicity studies, single and repeated (14 days) intravenous doses of up to 16 mg/kg were well tolerated with only pharmacologically related clinical signs seen in both studies. The no‐observed‐adverse‐effect level (NOAEL) was established at 16 mg/kg. Toxicokinetic examination demonstrated that ET‐26 hydrochloride showed a dose‐dependent increase to exposure, no gender difference, and no evidence of accumulation. [ABSTRACT FROM AUTHOR]

Statistical post‐processing approaches are widely employed to construct improved probabilistic meteorological forecasts from numerical weather prediction. However, generating calibrated and sharp probabilistic forecasts is challenging. In this article, a post‐processing approach, Mixture Probabilistic Model (MPM), is proposed to calibrate probabilistic ensemble forecasts subject to sharpness. In particular, the proposed MPM is applied to precipitation forecasting. First, the Censored and Shifted Gamma (CSG0) distribution is considered as the probability density function (PDF) for precipitation. Then, the predictive PDF of MPM is mixed by the individual PDFs which are fitted from raw ensemble members. Finally, to estimate optimal weight parameters for the mixture of individual PDFs, the Dirichlet distribution is utilized and the skills of the mixture model and individuals are both taken into consideration. The proposed MPM was tested using Innsbruck ensemble precipitation data and 6 h accumulated precipitation ensemble forecast data in east China from August to November 2017. Compared with raw forecasts and three state‐of‐the‐art post‐processing approaches, MPM showed improved performance for all verification scores. The quantitative and qualitative analyses of results in both cases indicate the potential and effectiveness of MPM for precipitation ensemble forecasting. [ABSTRACT FROM AUTHOR]

A rockburst prediction model of the entropy weight grey relational backpropagation (BP) neural network is developed. The model needs to select the evaluation factors according to the engineering practice and establish the sample library. The entropy weight method is used to calculate the objective weight of the characteristic factors, and the similarity between the samples is calculated by the combination of grey relational theory and the entropy method. The training sample of the BP neural network is selected by threshold determination. Finally, we use the trained neural network to estimate the rockburst intensity grade of samples to be tested. This model is applied to the rockburst prediction of Qamchiq tunnel project, and the prediction results are in good agreement with the actual conditions of the subsequent construction, thus verifying the feasibility and effectiveness of the model in the rockburst prediction. [ABSTRACT FROM AUTHOR]

Summary: Upland cotton (Gossypium hirsutum) is the world's largest source of natural fibre and dominates the global textile industry. Hybrid cotton varieties exhibit strong heterosis that confers high fibre yields, yet the genome‐wide effects of artificial selection that have influenced Upland cotton during its breeding history are poorly understood. Here, we resequenced Upland cotton genomes and constructed a variation map of an intact breeding pedigree comprising seven elite and 19 backbone parents. Compared to wild accessions, the 26 pedigree accessions underwent strong artificial selection during domestication that has resulted in reduced genetic diversity but stronger linkage disequilibrium and higher extents of selective sweeps. In contrast to the backbone parents, the elite parents have acquired significantly improved agronomic traits, with an especially pronounced increase in the lint percentage. Notably, identify by descent (IBD) tracking revealed that the elite parents inherited abundant beneficial trait segments and loci from the backbone parents and our combined analyses led to the identification of a core genomic segment which was inherited in the elite lines from the parents Zhong 7263 and Ejing 1 and that was strongly associated with lint percentage. Additionally, SNP correlation analysis of this core segment showed that a non‐synonymous SNP (A‐to‐G) site in a gene encoding the cell wall‐associated receptor‐like kinase 3 (GhWAKL3) protein was highly correlated with increased lint percentage. Our results substantially increase the valuable genomics resources available for future genetic and functional genomics studies of cotton and reveal insights that will facilitate yield increases in the molecular breeding of cotton. [ABSTRACT FROM AUTHOR]

Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades. MDSCs inhibit the antitumor immune response by suppressing T cell proliferation, cytokine production, and tumor cell killing. With MDSCs becoming novel targets in cancer therapy, our research has focused on the anti-MDSC function of Asparagus polysaccharide (AP), extracted from asparagus, a traditional Chinese herb. In this study, we have used MDSCs isolated from the spleen of mice with colon cancer as an in vitro model to assess the efficacy of AP. Treatment of MDSCs with AP significantly decreased cell proliferation and induced apoptotic cell death through a toll-like receptor 4 dependent way. Subsequent studies showed that the AP treatment enhanced the expression of Bax and Caspase-9 and inhibited the expression of Bcl-2, suggesting that AP induced apoptosis in the MDSCs via the intrinsic pathway. Altogether, the results showed that AP exhibited a significant anti-MDSC activity and attenuated suppression of the antitumor immune response, thereby indicating its potential use in cancer therapy. [ABSTRACT FROM AUTHOR]

Loss-of-function studies are critically important in gene functional analysis of model organisms and cells. However, conditional gene inactivation in diploid cells is difficult to achieve, as it involves laborious vector construction, multifold electroporation, and complicated genotyping. Here, a strategy is presented for generating biallelic conditional gene and DNA regulatory region knockouts in mouse embryonic stem cells by codelivery of CRISPR-Cas9 and short-homology-arm targeting vectors sequentially or simultaneously. Collectively, a simple and rapid method was presented to knock out any DNA element conditionally. This approach will facilitate the functional studies of essential genes and regulatory regions during development. [ABSTRACT FROM AUTHOR]

ABSTRACT While weather radar is widely used for quantitative precipitation estimation ( QPE) in China and many other countries, the performance of radar QPE is unsatisfactory. A major reason for inaccurate radar QPE is the application of conventional Z-R relationships. In this study the entire vertical profile of reflectivity ( VPR) is taken into consideration and a new relationship converting the VPR to rainfall rate is developed. The new relationship is obtained by a proposed terrain-based weighted random forests ( TWRF) method. The TWRF method regards 21 levels of constant altitude plan position indicator reflectivity (from 1 to 18 km) as features. The method consists of two parts: the first is to obtain subregions based on terrain, and the second is to refine the classical random forests method by computing feature weights based on correlation co-efficients between features and rainfall rate. Radar QPE based on the TWRF method was tested within the 45-100 km range of the radar in Hangzhou, China, on rainfall events in 2014. The proposed method showed improved performance for all verification scores over the Z-R relationship and the classical random forests method. Use of the entire VPR and the terrain-based study proved to be effective in this example. Experimental results indicate that the proposed TWRF method can improve the accuracy of radar QPE compared to an independent network of rain gauges. [ABSTRACT FROM AUTHOR]

The present phase II study aimed to compare the efficacy and safety of fospropofol disodium for injection (Fospropofol FD) and propofol when given during the induction of general anaesthesia in patients scheduled for elective surgery. Fospropofol FD is a water-soluble prodrug of propofol. Approved by the Ethical Committee, 240 participants aged 18-65 years were equally randomly allocated to receive an intravenous bolus of Fospropofol FD 20 mg/kg or propofol 2 mg/kg without any anaesthetic pre-treatment. The primary efficacy end-point was the sedation success rate within 5 min. after administering investigational drugs (the sedation success is defined as obtaining Modified Observer's Assessment of Alertness/Sedation scale score of 1). All the participants completed the induction and intubation within 25 min. after administration. The sedation success rates within 5 min. after administration of FospropofolFD 20 mg/kg and propofol 2 mg/kg were 94.50% versus 100% in the intention-to-treat population and 95.10% versus 100% in the per-protocol population, respectively. The non-inferiority test obtained a p-value less than 0.025, and the lower limits of the one-sided 97.5% confidence interval were more than −0.09. This meant that FospropofolFD 20 mg/kg was considered non-inferior to propofol 2 mg/kg for the primary efficacy end-point. Compared with propofol 2 mg/kg, FospropofolFD 20 mg/kg had a slower sedation efficacy. No serious adverse events were observed in the two groups. The sedation success rate within 5 min. after administration of FospropofolFD 20 mg/kg was non-inferior to propofol 2 mg/kg, and FospropofolFD 20 mg/kg can be used for the induction of general anaesthesia safely. [ABSTRACT FROM AUTHOR]

This study presents a guidance law to intercept non‐manoeuvring targets at a desired impact angle. The desired impact angle, defined in terms of a desired line‐of‐sight angle, is achieved by selecting the missile's lateral acceleration to enforce the sliding mode on a sliding surface. Then, the authors use the Lyapunov stability theory to prove the stability of the proposed non‐linear sliding surface. Furthermore, they introduce the adaptive neuro‐fuzzy inference system (ANFIS) to adaptively update the additional control command and reduce the high‐frequency chattering of sliding mode control (SMC). The proposed guidance law, denoted ANFSMC guidance law with impact angle constraint, combines the SMC methodology with ANFIS to enhance the robustness and reduce the chattering of the system. The effectiveness of the ANFSMC guidance law is also verified by the numerical simulations. [ABSTRACT FROM AUTHOR]

The bacterial clustered regularly interspaced short palindromic repeats ( CRISPR)/ CRISPR-associated 9 (Cas9) system is a versatile RNA-guided mammalian genome modification system. One-step generation of mouse genome targeting has been achieved by co-microinjection of one-cell stage embryos with Cas9 m RNA and small/single guide (sg) RNA. Many studies have focused on enhancing the efficiency of this system. In the present study, we report that simultaneous use of dual sg RNAs to target an individual gene significantly improved the Cas9-mediated genome targeting with a bi-allelic modification efficiency of up to 78%. We further observed that the target gene modifications were characterized by efficient germline transmission and site-dependent off-target effects, and also that the apolipoprotein E gene knockout-mediated defects in blood biochemical parameters were recapitulated by CRISPR/Cas9-mediated heritable gene modification. Our results provide a dual sg RNAs strategy to facilitate CRISPR/Cas9-mediated mouse genome targeting. [ABSTRACT FROM AUTHOR]

The emerging field of vascular composite allotransplantation (VCA) has become a clinical reality. Building upon cutting edge understandings of transplant surgery and immunology, complex grafts such as hands and faces can now be transplanted with success. Many of the challenges that have historically been limiting factors in transplantation, such as rejection and the morbidity of immunosuppression, remain challenges in VCA. Because of the accessibility of most VCA grafts, and the highly immunogenic nature of the skin in particular, VCA has become the focal point for cross-disciplinary approaches to developing novel approaches for some of the most challenging immunological problems in transplantation, particularly the early diagnoses and assessment of rejection. This paper provides a historically oriented introduction to the field of organ transplantation and the evolution of VCA. [ABSTRACT FROM AUTHOR]

Polymerization of vinyl acetate initiated by 2,2′-azobis(isobutyronitrile) at 75°C in the presence of iodine has been investigated. The process efficiently controls the number-average molecular weight and low polydispersities ( M w/ M n ≤ 1.52). Poly(vinyl acetate) with predetermined molecular weight and relatively low polydispersity was successfully synthesized. The polymerization was followed by online 1H-NMR spectra to investigate the evolution of several compounds in the reaction medium, especially the adduct of α-iodoisobutyronitrile ((CH3)2(CN)CI) between primary radicals and iodine. The structure of the end groups of poly(vinyl acetate) also was investigated using 1H-NMR spectra. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Proinflammatory agents trypsin and mast cell tryptase cleave and activate protease-activated receptor-2 (PAR-2), which is expressed on sensory nerves and causes neurogenic inflammation. P2X3 is a subtype of the ionotropic receptors for adenosine 5′-triphosphate (ATP), and is mainly localized on nociceptors. Here, we show that a functional interaction of the PAR-2 and P2X3 in primary sensory neurons could contribute to inflammatory pain. PAR-2 activation increased the P2X3 currents evoked by α, β, methylene ATP in dorsal root ganglia (DRG) neurons. Application of inhibitors of either protein kinase C (PKC) or protein kinase A (PKA) suppressed this potentiation. Consistent with this, a PKC or PKA activator mimicked the PAR-2-mediated potentiation of P2X3 currents. In the in vitro phosphorylation experiments, application of a PAR-2 agonist failed to establish phosphorylation of the P2X3 either on the serine or the threonine site. In contrast, application of a PAR-2 agonist induced trafficking of the P2X3 from the cytoplasm to the plasma membrane. These findings indicate that PAR-2 agonists may potentiate the P2X3, and the mechanism of this potentiation is likely to be a result of translocation, but not phosphorylation. The functional interaction between P2X3 and PAR-2 was also confirmed by detection of the α, β, methylene-ATP-evoked extracellular signal-regulated kinases (ERK) activation, a marker of neuronal signal transduction in DRG neurons, and pain behavior. These results demonstrate a functional interaction of the protease signal with the ATP signal, and a novel mechanism through which protease released in response to tissue inflammation might trigger the sensation to pain through P2X3 activation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the acupoint specificity by exploring the effective connectivity patterns of the poststimulus resting brain networks modulated by acupuncture at the PC6, with the same meridian acupoint PC7 and different meridian acupoint GB37. Materials and Methods: The functional MRI (fMRI) study was performed in 36 healthy right-handed subjects receiving acupuncture at three acupoints, respectively. Due to the sustained effects of acupuncture, a novel experimental paradigm using the nonrepeated event-related (NRER) design was adopted. Psychophysical responses (deqi sensations) were also assessed. Finally, a newly multivariate Granger causality analysis (mGCA) was used to analyze effective connectivity patterns of the resting fMRI data taken following acupuncture at three acupoints. Results: Following acupuncture at PC6, the red nucleus and substantia nigra emerged as central hubs, in comparison with the fusiform gyrus following acupuncture at GB37. Red nucleus was also a target following acupuncture at PC7, but with fewer inputs than those of PC6. In addition, the most important target following acupuncture at PC7 was located at the parahippocampus. Conclusion: Our findings demonstrated that acupuncture at different acupoints may exert heterogeneous modulatory effects on the causal interactions of brain areas during the poststimulus resting state. These preliminary findings provided a clue to elucidate the relatively function-oriented specificity of acupuncture effects. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A novel algorithm exploiting joint intra channel colour correlation and inter channel colour difference is presented for interpolating colour filter array data. Experiments on standard database and comparisons with other state‐of‐the‐art methods demonstrate that the joint intra and inter information is effective and comparable. [ABSTRACT FROM AUTHOR]

Summary: It is difficult to protect users' privacy and to process private information due to the complexity and uncertainty of such information. To protect private information quickly and accurately, a many‐objective optimization algorithm framework based on the hybrid elite selection strategy is proposed in this paper. First, a mating selection mechanism combined with the achievement scale function and angle information index is used to generate elite offspring of the internal population. Then, the balanceable fitness estimation method is employed to select and update the external archive. To test performance, the proposed algorithm is tested on many‐objective optimization problems (MaOPs) and compared with five state‐of‐the‐art algorithms. Experimental simulation results show that the proposed algorithm is more effective in solving MaOPs and can inspire development of a better privacy protection strategy. [ABSTRACT FROM AUTHOR]

An abstract of the article "Synthesis of 1-Arylsulfonyl-1,2,3-triazoles from (Z)-Arylvinyl Bromides by Sequential Elimination-Cycloaddition Reaction" by Wensheng Zhang and colleagues is presented.

An abstract of the article "Stereoselective Synthesis of (Z)-β-Arylvinyl Bromides from anti-2,3-Dibromo-3-arylpropanoic Acids" by Wenjing Xv, Wensheng Zhang, Fei Zhang, and Chunxiang Kuang is presented.

via an Ullmann-type reaction of (E)-arylvinyl bromides (I) with phenols (II) [ABSTRACT FROM AUTHOR]

Study of functional brain network (FBN) based on functional magnetic resonance imaging (fMRI) has proved successful in depression disorder classification. One popular approach to construct FBN is Pearson correlation. However, it only captures pairwise relationship between brain regions, while it ignores the influence of other brain regions. Another common issue existing in many depression disorder classification methods is applying only single local feature extracted from constructed FBN. To address these issues, we develop a new method to classify fMRI data of patients with depression and healthy controls. First, we construct the FBN using a sparse low-rank model, which considers the relationship between two brain regions given all the other brain regions. Moreover, it can automatically remove weak relationship and retain the modular structure of FBN. Secondly, FBN are effectively measured by eight graph-based features from different aspects. Tested on fMRI data of 31 patients with depression and 29 healthy controls, our method achieves 95% accuracy, 96.77% sensitivity, and 93.10% specificity, which outperforms the Pearson correlation FBN and sparse FBN. In addition, the combination of graph-based features in our method further improves classification performance. Moreover, we explore the discriminative brain regions that contribute to depression disorder classification, which can help understand the pathogenesis of depression disorder. [ABSTRACT FROM AUTHOR]