Publications by authors named "Wensheng Zhang"

253 Publications

Combined Transcriptome and Proteome Analysis to Elucidate Salt Tolerance Strategies of the Halophyte Retz.

Front Plant Sci 2021 2;12:760589. Epub 2021 Nov 2.

Chinese Academy of Sciences Engineering Laboratory for Efficient Utilization of Saline Resources, Center for Agricultural Resources Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Shijiazhuang, China.

, a C4 monocot, has the potential to reclaim saline and drylands and to be utilized as fodder and forage. Its adaptability to survive saline stress has been proven with eco-physiological and biochemical studies. However, little is known about its molecular mechanisms of salt tolerance. In this study, an integrated transcriptome and proteome analysis approach, based on RNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS), was used to identify the said mechanisms. Plants were treated with control (0 mM), low (100 mM), and high (300 mM) sodium chloride (NaCl) treatments to distinguish beneficial and toxic pathways influencing plant biomass. The results indicated differential expression of 3,179 (1,126 upregulated/2,053 downregulated) and 2,172 (898 upregulated/1,274 downregulated) genes (DEGs), and 514 (269 upregulated/245 downregulated) and 836 (494 upregulated/392 downregulated) proteins (DEPs) at 100 and 300 mM NaCl, respectively. Among these, most upregulated genes and proteins were involved in salt resistance strategies such as proline biosynthesis, the antioxidant defense system, ion homeostasis, and sugar accumulation at low salinity levels. On the other hand, the expression of several genes and proteins involved in the respiratory process were downregulated, indicating the inability of plants to meet their energy demands at high salinity levels. Moreover, the impairments in photosynthesis were also evident with the reduced expression of genes regulating the structure of photosystems and increased expression of abscisic acid (ABA) mediated pathways which limits stomatal gas exchange. Similarly, the disturbance in fatty acid metabolism and activation of essential ion transport blockers damaged the integrity of the cell membrane, which was also evident with enhanced malondialdehyde (MDA). Overall, the analysis of pathways revealed that the plant optimal performance at low salinity was related to enhanced metabolism, antioxidative defense, cell growth, and signaling pathways, whereas high salinity inhibited biomass accumulation by altered expression of numerous genes involved in carbon metabolism, signaling, transcription, and translation. The data provided the first global analysis of the mechanisms imparting salt stress tolerance of any halophyte at transcriptome and proteome levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.760589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598733PMC
November 2021

Interventional treatment for acute cerebral infarction with large vessel occlusion combined with aortic arch interruption: A case report.

Medicine (Baltimore) 2021 Nov;100(46):e27879

Department of Neurology, Heyuan People's Hospital, Guangdong Provincial People's Hospital Heyuan Hospital, Guangdong Province, China.

Rationale: Aortic arch interruption is a type of congenital vascular malformation that is often observed in childhood. Most children die of congestive heart failure due to rapid deterioration. Children can only survive to adulthood if they have extremely rich collateral circulation. Cases of acute cerebral infarction with large vessel occlusion receiving interventional treatment in adult patients with interrupted aortic arch have not been reported.

Patient Concerns: A 55-year-old man with a history of atrial fibrillation and smoking but without a family history of stroke was admitted to our hospital with a 5-hour history of left limb weakness and speech difficulties.

Diagnoses: Emergency brain computed tomography showed a large cerebral infarction in the right frontal temporal parietal lobe. He was suspected to have aortic arch interruption in the early stage of endovascular interventional therapy through the femoral artery approach, and was converted to the transradial artery pathway. The aortic arch was disconnected, and the right internal carotid artery was occluded.

Interventions: Considering the possibility of cardiogenic embolism, a middle catheter was used for thrombus aspiration of the right internal carotid artery. After removal of the dark red thrombus was removed, the right internal carotid artery was successfully recanalized.

Outcomes: The patient recovered well after the operation. However, the patient and his family refused further treatment for aortic arch interruption. The modified Rankin Scale score was 0 at 3 months and 1 year of follow-up which meant that he recovered quite well.

Lessons: Adult patients with acute cerebral infarction with large vessel occlusion are rarely complicated with aortic arch interruption, and emergency thrombectomy via the radial artery approach is feasible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000027879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601316PMC
November 2021

Integrated BIM and VR to implement IPD mode in transportation infrastructure projects: System design and case application.

PLoS One 2021 11;16(11):e0259046. Epub 2021 Nov 11.

School of Traffic and Transportation, Shijiazhuang Tiedao University, Shijiazhuang, China.

The complex design of transportation infrastructure hinders communication between different roles in the project, which makes it difficult to promote the Integrated Project Delivery (IPD) mode. This paper discusses a design simulation and communication system based on Building Information Modeling and Virtual Reality for transportation infrastructure (DSC-BV-TI system), integrated with BIM, with VR developed by using a game engine. Based on an analysis of the user's demand, the system introduces a three-dimensional BIM model of traffic infrastructure in an immersive VR environment and realizes the simulation design, weather simulation, virtual driving, sight distance calculation, visual simulation and other functions of traffic infrastructure project by using the system's safety assessment and scheme decision. The system is applied to the design of the Jinjiazhuang Extra-Long Tunnel project of the Yan-Chong Expressway in Hebei Province, which was built for the 2022 Winter Olympics. The results show that, using the DSC-BV-TI system, the designer has completed a display of the overall scheme: the user can use the steering wheel to drive a vehicle; use the head-mounted display to play the picture; realize the simulation and interaction in a variety of simulated weather conditions and environments; and use IPD mode to communicate and make decisions on the design scheme of the traffic infrastructure, tunnel speed limit and other aspects that play a key role. The DSC-BV-TI system has 8 advantages and 4 disadvantages identified through a questionnaire survey, the advantages including high fidelity, high efficiency and low cost. At the same time, according to the research results, three suggestions to help improve the system are discussed. DSC-BV-TI system as a communication bridge between the design team and other stakeholders reduces the communication gap and promotes the implementation of the IPD mode in transportation infrastructure projects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259046PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584753PMC
November 2021

Opioids for the Prevention of Post-dural Puncture Headache in Obstetrics: A Systematic Review and Meta-analysis of Efficacy and Safety.

Pain Physician 2021 Nov;24(7):E1155-E1162

Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Background: Post-dural puncture headache (PDPH), or spinal headache, is the most common serious complication resulting from iatrogenic puncture of the dura during epidural or spinal anesthesia and cerebrospinal fluid (CSF) leak in pregnant women.

Objective: To analyze the effectiveness and safety of opioids as a prophylaxis approach in treating obstetric patients who underwent unintentional dural puncture during the initiation of neuraxial anesthesia.

Study Design: A systematice review and meta-analysis.

Setting: No restriction regarding study type.

Methods: PubMed, Embase, and the Cochrane library were searched for available papers published up to September 2020.

Results: According to the eligibility criteria, 10 studies were included with post-dural puncture headache (PDPH) incidence as the primary outcome and the number of epidural blood patch (EBP) required as the second outcome. The risk estimates of each study were reported as odds ratios (ORs). The results showed morphine does not decrease the incidence of PDPH (OR = 0.45, 95% CI: 0.15 - 1.34, P = 0.153, I2 = 74.4%, Pheterogeneity = 0.004) and the use of EBP (OR = 0.40, 95% CI: 0.08 - 1.95, P = 0.259, I2=73.7%, Pheterogeneity = 0.004). Fentanyl does not decrease the incidence of PDPH (OR = 0.35, 95% CI: 0.01-13.77, P = 0.576, I2 = 81.0%, Pheterogeneity = 0.022).

Limitations: The small number of included studies, high heterogeneity, and variety in study designs.

Conclusions: Exposure to opioids for any reason after the diagnosis of unintentional dural puncture is not associated with a reduced risk of PDPH and does not decrease the need for therapeutic EBP.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2021

A Modified SMART-Seq Method for Single-Cell Transcriptomic Analysis of Embryoid Body Differentiation.

Methods Mol Biol 2021 Oct 19. Epub 2021 Oct 19.

Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Embryoid bodies (EBs) are aggregate of cells that contain three embryonic germ layers. They can be formed by direct differentiation from pluripotent embryonic stem cells (ESCs), which serves as a useful model for understanding early embryo development. Due to the mixture of different cell types, it is necessary to investigate EBs at the single-cell level. Here, we describe a robust and straightforward method for single-cell gene expression profiling during mouse EB differentiation from mouse ESCs (mESCs). The protocol is modified from a widely used method in the SMART-seq family, which only requires standard molecular biology techniques and lab equipment. It allows for accurate 3' counting of transcript at the single-cell level, which helps reveal cellular identities during EB formation. Combined with perturbation experiments, the method provides an opportunity for mechanistic studies of embryo development at the single-cell level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/7651_2021_435DOI Listing
October 2021

Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities.

Front Pharmacol 2021 16;12:678437. Epub 2021 Sep 16.

Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, China.

lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine's toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity were quantitively investigated. the effectiveness for lido-OH was studied using mouse tail nerve block, rat dorsal subcutaneous infiltration, and rat sciatic nerve block models. The systemic toxicities for lido-OH were evaluated with altered state of consciousness (ASC), arrhythmia, and death in mice. Lidocaine and saline were used as positive and negative control, respectively. The dose-effect relationships were analyzed. the half effective-concentration for lido-OH were 2.1 mg/ml with 95% confident interval (CI95) 1.6-3.1 (lidocaine: 3.1 mg/ml with CI95 2.6-4.3) in tail nerve block, 8.2 mg/ml with CI95 8.0-9.4 (lidocaine: 6.9 mg/ml, CI95 6.8-7.1) in sciatic nerve block, and 5.9 mg/ml with CI95 5.8-6.0 (lidocaine: 3.1 mg/ml, CI95 2.4-4.0) in dorsal subcutaneous anesthesia, respectively. The magnitude and duration of lido-OH were similar with lidocaine. The half effective doses (ED) of lido-OH for ACS was 45.4 mg/kg with CI95 41.6-48.3 (lidocaine: 3.1 mg/kg, CI95 1.9-2.9), for arrhythmia was 16.0 mg/kg with CI95 15.4-16.8 (lidocaine: 3.0 mg/kg, CI95 2.7-3.3), and for death was 99.4 mg/kg with CI95 75.7-124.1 (lidocaine: 23.1 mg/kg, CI95 22.8-23.4). The therapeutic index for lido-OH and lidocaine were 35.5 and 5.6, respectively. compared with lidocaine, lido-OH produced local anesthesia at similar potency and efficacy, but with significantly reduced systemic toxicities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.678437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481665PMC
September 2021

High-Loading Self-Assembling Peptide Nanoparticles as a Lipid-Free Carrier for Hydrophobic General Anesthetics.

Int J Nanomedicine 2021 11;16:5317-5331. Epub 2021 Aug 11.

Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Purpose: Typical hydrophobic amino acids (HAAs) are important motifs for self-assembling peptides (SAPs), but they lead to low water-solubility or compact packing of peptides, limiting their capacity for encapsulating hydrophobic drugs. As an alternative, we designed a peptide GQY based on atypical HAAs, which could encapsulate hydrophobic drugs more efficiently. Although hydrophobic general anesthetics (GAs) have been formulated as lipid emulsions, their lipid-free formulations have been pursued because of some side effects inherent to lipids. Using GAs as targets, potential application of GQY as a carrier for hydrophobic drugs was evaluated.

Methods: Thioflavin-T (ThT) binding test, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to examine the self-assembling ability of GQY. Pyrene and 8-Anilino-1-naphthalenesulfonic acid (ANS) were used to confirm formation of hydrophobic domain in GQY nanoparticles. Using pyrene as a model, GQY's capacity to encapsulate hydrophobic drugs was evaluated. GAs including propofol, etomidate and ET26 were encapsulated by GQY. Loss of righting reflex (LORR) test was conducted to assess the anesthetic efficacy of these lipid-free formulations. Paw-licking test was used to evaluate pain-on-injection of propofol-GQY (PROP-GQY) formulation. Hemolytic and cytotoxicity assay were used to evaluate biocompatibility of GQY.

Results: Stable nanoparticles containing plenty of hydrophobic cavities could be formed by GQY, which could encapsulate hydrophobic drugs at very high concentration and form stable suspensions. Propofol, etomidate and ET26 formulated by GQY showed anesthetic efficacy comparable to their currently available formulations. Unlike clinic lipid emulsion, PROP-GQY formulation did not cause pain-on-injection in rats. Neither obvious cytotoxicity nor hemolytic activity of GQY was observed.

Conclusion: GQY could encapsulate GAs to obtain stable and effective formulations. As a lipid-free carrier, GQY exhibited considerable biocompatibility and other side benefits such as reducing pain-on-injection. More SAPs based on atypical HAAs could be designed as promising carriers for hydrophobic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S315310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364852PMC
November 2021

Long Non-coding RNA Signatures Associated With Liver Aging in Senescence-Accelerated Mouse Prone 8 Model.

Front Cell Dev Biol 2021 22;9:698442. Epub 2021 Jul 22.

Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai, China.

The liver is sensitive to aging because the risk of hepatopathy, including fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, increases dramatically with age. Long non-coding RNAs (lncRNAs) are >200 nucleotides long and affect many pathological and physiological processes. A potential link was recently discovered between lncRNAs and liver aging; however, comprehensive and systematic research on this topic is still limited. In this study, the mouse liver genome-wide lncRNA profiles of 8-month-old SAMP8 and SAMR1 models were explored through deep RNA sequencing. A total of 605,801,688 clean reads were generated. Among the 2,182 identified lncRNAs, 28 were differentially expressed between SAMP8 and SAMR1 mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) surveys showed that these substantially dysregulated lncRNAs participated in liver aging from different aspects, such as lipid catabolic (GO: 0016042) and metabolic pathways. Further assessment was conducted on lncRNAs that are most likely to be involved in liver aging and related diseases, such as LNC_000027, LNC_000204E, NSMUST00000144661.1, and ENSMUST00000181906.1 acted on Ces1g. This study provided the first comprehensive dissection of lncRNA landscape in SAMP8 mouse liver. These lncRNAs could be exploited as potential targets for the molecular-based diagnosis and therapy of age-related liver diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.698442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339557PMC
July 2021

p53 Inhibition Provides a Pivotal Protective Effect against Cerebral Ischemia-Reperfusion Injury via the Wnt Signaling Pathway.

Cerebrovasc Dis 2021 Aug 2:1-9. Epub 2021 Aug 2.

Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, China.

Introduction: Cerebral ischemia-reperfusion injury enhances brain injury and increases its morbidity and mortality. The purpose of our study was to further explore the specific pathogenesis of cerebral ischemia disease by studying the role of p53 in cerebral ischemia-reperfusion injury and its mechanism to provide a new target for the treatment of cerebral ischemia.

Methods: Middle cerebral artery occlusion (MCAo) was established in rats. The changes in p53 and apoptotic proteins in the rat model were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The effects of p53 inhibitors on cerebral is-chemia-reperfusion injury in rats were evaluated by modified neurological severity score (mNSS) and infarct area. Subsequently, neural stem cells (NSCs) were isolated and cultured in vitro, and oxygen and glucose deprivation (OGD) was induced to establish an in vitro ischemia-reperfusion injury model. Cell viability and migration were detected by CCK-8 and transwell assays. Apoptosis of NSCs was detected by flow cytometry. Finally, protein expression in the Wnt pathway activated by p53 was detected by Western blotting.

Results: Compared with the sham group, p53 levels, mNSS, cerebral infarction area, and apoptosis were significantly increased in the MCAo group (p < 0.05). When the p53 inhibitor PFT-α was injected, the increase in these levels was reversed. Also, the viability and migration of cells decreased and apo-ptosis increased in the in vitro OGD model, whereas the viability, migration, and apoptosis were significantly reversed after the addition of p53 inhibitors (p < 0.05). Finally, p53 induced Wnt signaling pathway proteins β-catenin and cyclin D1 decrease in the MCAo group, while p53 inhibitors reversed their inhibitory effect on the Wnt signaling pathway.

Conclusion: We confirmed in vivo and in vitro that inhibition of p53 has a protective effect on the cerebral ischemia-reperfusion injury, which may be related to the activation of the Wnt signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516889DOI Listing
August 2021

Medical image management and analysis system based on web for fungal keratitis images.

Math Biosci Eng 2021 04;18(4):3667-3679

Inspur Group Ltd, Jinan 250011, China.

The medical image management and analysis system proposed in this paper is a medical software developed by the Browser/Server (B/S) architecture after investigating the workflow of the relevant departments of the hospital, which realizes the entire process of patients from consultation to printing of reports. The computer-aided diagnosis function is added based on image management. Due to the difficulty in collecting medical image data, in the computer-aided diagnosis module, this paper only uses the common fungal keratitis collected from the hospital in the laboratory. Focused microscope images are used for experiments. First, the images were trained with three convolutional neural networks, AlexNet, ZFNet, and VGG16. These models which classify fungal keratitis were obtained and integrated was performed to obtain better classification results. Finally, the model was integrated with the system designed in this paper, which realized the automatic diagnosis of Confocal Microscopy (CM) images of fungal keratitis online and provided it to medical staff for reference. The system can improve the work efficiency of the image-related departments while reducing the workload of doctors in the department to manually read the films.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3934/mbe.2021183DOI Listing
April 2021

LncRNA ITGB2-AS1 promotes the progression of clear cell renal cell carcinoma by modulating miR-328-5p/HMGA1 axis.

Hum Cell 2021 Sep 25;34(5):1545-1557. Epub 2021 Jun 25.

Department of Urology, The First People's Hospital of Jiujiang in Jiangxi Province, Affiliated Medical College of Jiujiang Hospital, Nanchang University, No. 48, Taling South Road, Xunyang District, Jiujiang City, 332000, Jiangxi Province, China.

Clear cell renal cell carcinoma (ccRCC) is the most common histologic subtype of renal cell carcinoma and long non-coding RNAs (lncRNAs) play important roles in the progression of ccRCC. In this study, we aim to explore the potential function of ITGB2-AS1 in ccRCC progression and its underlying molecular mechanism. We first explored the association between ITGB2-AS1 expression level and ccRCC prognosis. We found that the expression level of ITGB2-AS1 was significantly higher in ccRCC tumor and cell lines, and highly expressed ITGB2-AS1 was also associated with a poorer prognosis. Consistently, silencing ITGB2-AS1 inhibited proliferation, promoted apoptosis in ccRCC cell lines, and curbed the tumorigenesis in the Xenograft model, reduced tumorigenesis in a xenograft tumor growth model. We further identified and confirmed the miRNA miR-328-5p as a target of ITGB2-AS1, and miR-328-5p negatively regulated the expression of HMGA1 protein. The anti-tumor effect of silencing ITGB2-AS1 could be partially rescued by inhibiting miR-328-5p activity or overexpressing HMGA1, indicating that ITGB2-AS1 promotes the survival and progression of ccRCC by modulating miR-328-5p/HMGA1 axis. Collectively, our data demonstrated that ITGB2-AS1 expression level is positively correlated with the survival and tumorigenesis of ccRCC. As a target of ITGB2-AS1, miR-328-5p seems to function as a tumor-suppressor, and the oncogenic effect of ITGB2-AS1 is partially mediated via the miR-328-5p/HMGA1 axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13577-021-00563-7DOI Listing
September 2021

Joint Sparse Locality-Aware Regression for Robust Discriminative Learning.

IEEE Trans Cybern 2021 Jun 24;PP. Epub 2021 Jun 24.

With the dramatic increase of dimensions in the data representation, extracting latent low-dimensional features becomes of the utmost importance for efficient classification. Aiming at the problems of weakly discriminating marginal representation and difficulty in revealing the data manifold structure in most of the existing linear discriminant methods, we propose a more powerful discriminant feature extraction framework, namely, joint sparse locality-aware regression (JSLAR). In our model, we formulate a new strategy induced by the nonsquared LS₂ norm for enhancing the local intraclass compactness of the data manifold, which can achieve the joint learning of the locality-aware graph structure and the desirable projection matrix. Besides, we formulate a weighted retargeted regression to perform the marginal representation learning adaptively instead of using the general average interclass margin. To alleviate the disturbance of outliers and prevent overfitting, we measure the regression term and locality-aware term together with the regularization term by forcing the row sparsity with the joint L2,1 norms. Then, we derive an effective iterative algorithm for solving the proposed model. The experimental results over a range of benchmark databases demonstrate that the proposed JSLAR outperforms some state-of-the-art approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2021.3080128DOI Listing
June 2021

Safety Pharmacology Study of ET-26 Hydrochloride, a Potential Drug for Intravenous General Anesthesia, in Rats and Beagle Dogs.

Front Pharmacol 2021 31;12:679381. Epub 2021 May 31.

Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.

ET-26 hydrochloride (ET-26HCl), a class 1 new drug, was developed to reserve the advantages of etomidate with a mild adrenocortical inhibition. this study was to evaluate the potential adverse effects on the cardiovascular system of beagle dogs and the respiratory and central nervous systems of rats. three established methods, the whole-body plethysmography for respiratory function, the prototype telemetry transmitter for cardiovascular function, and the standardized functional observational battery for central nervous system function, were accomplished with Good Laboratory Practice standards. no significant difference in the tidal volume, but the respiratory rate and minute ventilation were reduced. The degree of inhibition was the most serious in the first 15 min after dosing and function fully recovered after 1 h. For male rats, the respiratory rate of male rats was reduced significantly at 15 min after injection with ET-26HCl (4 mg/kg, 28.6%, ≤ 0.01; 8 mg/kg, 24.5%, ≤ 0.01; 16 mg/kg, 44.5%, ≤ 0.001), and the minute ventilation at 15 min was decreased by 20.1% (4 mg/kg, = 0.034), 22.2% (8 mg/kg, = 0.019), and 44.6% (16 mg/kg, ≤ 0.001) as compared to control group. As with male rats, the respiratory rate of the female rats was reduced significantly at 15 min (4 mg/kg, 23.3%, ≤ 0.01; 8 mg/kg, 29.2%, ≤ 0.001; 16 mg/kg, 44.1%, ≤ 0.001), and the minute ventilation was decreased by 25.2% (4 mg/kg, ≤ 0.001), 23.0% (8 mg/kg, ≤ 0.01), and 47.6% (16 mg/kg, ≤ 0.001). Then, all the variations in cardiovascular functions were within the expected range for normal biological variation, we concluded that ET-26HCl, even at 10-fold ED, still does not exert toxicological effects on the cardiovascular system. For male beagle dogs, the systolic blood pressure after 24 h following administration of vehicle control or 8, 12, or 16 mg/kg ET-26HCl was 137.80 ± 5.55, 131.76 ± 10.03, 139.88 ± 8.35, and 141.28 ± 8.75 mmHg, respectively. The diastolic blood pressure was 71.16 ± 4.84, 66.52 ± 8.50, 73.64 ± 8.51, and 74.24 ± 8.68 mmHg, respectively. For female beagle dogs, the systolic blood pressure after 24 h following administration of vehicle control or 8, 12, or 16 mg/kg ET-26HCl was 128.28 ± 5.22, 124.76 ± 7.29, 134.88 ± 5.56, and 135.36 ± 8.72 mmHg, respectively. The diastolic blood pressure was 67.00 ± 4.10, 62.12 ± 7.87, 69.44 ± 6.40, and 70.20 ± 8.42 mmHg, respectively. In central nervous system function experiment, all the changes observed in the functional observational battery tests, including motor activity, behavior, coordination, and sensory and motor reflex responses, and reduced body temperature, were resulted in general anesthesia effect of ET-26HCl. ET-26HCl exerts mild, reversible effects on respiratory, cardiovascular, and central nervous system function as verified by standard animal models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.679381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201096PMC
May 2021

Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.

Eur J Pharm Sci 2021 Sep 8;164:105904. Epub 2021 Jun 8.

Department of Anesthesiology, West China Hospital, Sichuan University & The Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, China. Electronic address:

Objective: Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial.

Methods: A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests.

Results: In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750).

Conclusions: Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2021.105904DOI Listing
September 2021

SEC61G promotes breast cancer development and metastasis via modulating glycolysis and is transcriptionally regulated by E2F1.

Cell Death Dis 2021 05 27;12(6):550. Epub 2021 May 27.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Breast cancer is the most common cancer in women and its incidence rates are rapidly increasing in China. Understanding the molecular mechanisms of breast cancer tumorigenesis enables the development of novel therapeutic strategies. SEC61G is a subunit of the endoplasmic reticulum translocon that plays critical roles in various tumors. We aimed to investigate the expression and function of SEC61G in breast cancer. By analyzing The Cancer Genome Atlas breast cancer cohort, we found that SEC61G was highly expressed in breast cancer and predicted poor prognosis of breast cancer patients. Overexpression of SEC61G and its prognostic role was also confirmed in the Nanjing Medical University (NMU) breast cancer cohort. Functionally, we demonstrated that knockdown of SEC61G suppressed breast cancer cell proliferation, migration, invasion, and promoted breast cancer cell apoptosis in vitro. Xenograft breast tumor model revealed that knockdown of SEC61G inhibited breast tumor development in vivo. Furthermore, we demonstrated that SEC61G positively regulated glycolysis in breast cancer cells. Mechanistically, we showed that transcription factor E2F1 directly bound to the promoter of SEC61G and regulated its expression in breast cancer cells. SEC61G overexpression antagonized the effect of E2F1 knockdown in regulating breast cancer cell proliferation, invasion, and apoptosis. Finally, we demonstrated that the E2F1/SEC61G axis regulated glycolysis and chemo-sensitivity of Herceptin in breast cancer cells. Taken together, these results of in vitro and in vivo studies demonstrate that SEC61G promotes breast cancer development and metastasis via modulating glycolysis and is transcriptionally regulated by E2F1, which might be utilized as a promising therapeutic target of breast cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03797-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155024PMC
May 2021

Robust Collaborative Learning of Patch-Level and Image-Level Annotations for Diabetic Retinopathy Grading From Fundus Image.

IEEE Trans Cybern 2021 May 7;PP. Epub 2021 May 7.

Diabetic retinopathy (DR) grading from fundus images has attracted increasing interest in both academic and industrial communities. Most convolutional neural network-based algorithms treat DR grading as a classification task via image-level annotations. However, these algorithms have not fully explored the valuable information in the DR-related lesions. In this article, we present a robust framework, which collaboratively utilizes patch-level and image-level annotations, for DR severity grading. By an end-to-end optimization, this framework can bidirectionally exchange the fine-grained lesion and image-level grade information. As a result, it exploits more discriminative features for DR grading. The proposed framework shows better performance than the recent state-of-the-art algorithms and three clinical ophthalmologists with over nine years of experience. By testing on datasets of different distributions (such as label and camera), we prove that our algorithm is robust when facing image quality and distribution variations that commonly exist in real-world practice. We inspect the proposed framework through extensive ablation studies to indicate the effectiveness and necessity of each motivation. The code and some valuable annotations are now publicly available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2021.3062638DOI Listing
May 2021

Comprehensive Analysis of Multiple Cohort Datasets Deciphers the Utility of Germline Single-Nucleotide Polymorphisms in Prostate Cancer Diagnosis.

Cancer Prev Res (Phila) 2021 Jul 17;14(7):741-752. Epub 2021 Apr 17.

Bioinformatics Core of Xavier NIH RCMI Center of Cancer Research, Xavier University of Louisiana, New Orleans, LA 70125, USA.

Prostate cancer susceptibility is a polygenic trait. We aimed to examine the controversial diagnostic utility of single-nucleotide polymorphisms (SNP) for prostate cancer. We analyzed two datasets collected from Europeans and one from Africans. These datasets were generated by the genome-wide association studies, that is, CGEMS, BPC3, and MEC-Africans, respectively. About 540,000 SNPs, including 61 risk markers that constitute a panel termed MK-61, were commonly genotyped. For each dataset, we augmented the MK-61 panel to generate an MK-61 one by adding several thousands of SNPs that were moderately associated with prostate cancer occurrence in external dataset(s). We assessed the diagnostic utility of both panels by measuring their predictive strength for prostate cancer occurrence with AUC statistics. We calculated the theoretical AUCs using quantitative genetics model-based formulae and obtained the empirical estimates via 10-fold cross-validation using statistical and machine learning techniques. For the MK-61 panel, the 95% confidence intervals of the theoretical AUCs (AUC-CI.95) were 0.578-0.655, 0.596-0.656, and 0.539-0.596 in the CGEMS, BPC3, and MEC-Africans cohorts, respectively. For the MK-61 panels, the corresponding AUC-CI.95 were 0.617-0.663, 0.527-0.736, and 0.547-0.565. The empirical AUCs largely fell within the theoretical interval. A promising result (AUC = 0.703, FNR = 0.354, FPR = 0.353) was obtained in the BPC3 cohort when the MK-61 panel was used. In the CGEMS cohort, the MK-61 panel complemented PSA in predicting the disease status of PSA ≥ 2.0 ng/mL samples. This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with [Formula: see text]ng/mL. PREVENTION RELEVANCE: This study demonstrates that augmented risk SNP panels can enhance prostate cancer prediction for males of European ancestry, especially those with PSA ≥ 2 ng/mL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-20-0534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295202PMC
July 2021

The 14-day repeated-dose toxicity studies of a fixed-dose combination, QXOH/levobupivacaine, via subcutaneous injection in mice.

J Appl Toxicol 2021 Nov 5;41(11):1747-1764. Epub 2021 Apr 5.

Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.4168DOI Listing
November 2021

Quantitative Proteomic Profiling Identifies a Potential Novel Chaperone Marker in Resistant Breast Cancer.

Front Oncol 2021 25;11:540134. Epub 2021 Feb 25.

Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, United States.

Development of aromatase inhibitor resistant breast cancer among postmenopausal women continues to be a major clinical obstacle. Previously, our group demonstrated that as breast cancer cells transition from hormone-dependent to hormone-independent, they are associated with increased growth factor signaling, enhanced cellular motility, and the epithelial to mesenchymal transition (EMT). Given the complexity of cancer stem cells (CSC) and their implications on endocrine resistance and EMT, we sought to understand their contribution towards the development of aromatase inhibitor resistant breast cancer. Cells cultured three dimensionally as mammospheres are enriched for CSCs and more accurately recapitulates tumors . Therefore, a global proteomic analysis was conducted using letrozole resistant breast cancer cells (LTLT-Ca) mammospheres and compared to their adherent counterparts. Results demonstrated over 1000 proteins with quantitative abundance ratios were identified. Among the quantified proteins, 359 were significantly altered ( < 0.05), where 173 were upregulated and 186 downregulated ( < 0.05, fold change >1.20). Notably, midasin, a chaperone protein required for maturation and nuclear export of the pre-60S ribosome was increased 35-fold. Protein expression analyses confirmed midasin is ubiquitously expressed in normal tissue but is overexpressed in lobular and ductal breast carcinoma tissue as well as ER+ and ER- breast cancer cell lines. Functional enrichment analyses indicated that 19 gene ontology terms and one KEGG pathway were over-represented by the down-regulated proteins and both were associated with protein synthesis. Increased midasin was strongly correlated with decreased relapse free survival in hormone independent breast cancer. For the first time, we characterized the global proteomic signature of CSC-enriched letrozole-resistant cells associated with protein synthesis, which may implicate a role for midasin in endocrine resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.540134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951058PMC
February 2021

Npac Is a Co-factor of Histone H3K36me3 and Regulates Transcriptional Elongation in Mouse Embryonic Stem Cells.

Genomics Proteomics Bioinformatics 2021 Mar 3. Epub 2021 Mar 3.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China. Electronic address:

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a "reader" of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC (mESC) pluripotency since knockdown of Npac causes mESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our Npac ChIP-seq results reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with p-TEFb, RNA Pol II Ser2, and Ser5. Depletion of Npac disrupts transcriptional elongation of pluripotency genes Nanog and Rif1. Taken together, we propose that Npac is essential for transcriptional elongation of pluripotency genes by recruiting of p-TEFb and interacting with RNA Pol II Ser2 and Ser5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gpb.2020.08.004DOI Listing
March 2021

One-Step Multiview Subspace Segmentation via Joint Skinny Tensor Learning and Latent Clustering.

IEEE Trans Cybern 2021 Mar 4;PP. Epub 2021 Mar 4.

Multiview subspace clustering (MSC) has attracted growing attention due to the extensive value in various applications, such as natural language processing, face recognition, and time-series analysis. In this article, we are devoted to address two crucial issues in MSC: 1) high computational cost and 2) cumbersome multistage clustering. Existing MSC approaches, including tensor singular value decomposition (t-SVD)-MSC that has achieved promising performance, generally utilize the dataset itself as the dictionary and regard representation learning and clustering process as two separate parts, thus leading to the high computational overhead and unsatisfactory clustering performance. To remedy these two issues, we propose a novel MSC model called joint skinny tensor learning and latent clustering (JSTC), which can learn high-order skinny tensor representations and corresponding latent clustering assignments simultaneously. Through such a joint optimization strategy, the multiview complementary information and latent clustering structure can be exploited thoroughly to improve the clustering performance. An alternating direction minimization algorithm, which owns low computational complexity and can be run in parallel when solving several key subproblems, is carefully designed to optimize the JSTC model. Such a nice property makes our JSTC an appealing solution for large-scale MSC problems. We conduct extensive experiments on ten popular datasets and compare our JSTC with 12 competitors. Five commonly used metrics, including four external measures (NMI, ACC, F-score, and RI) and one internal metric (SI), are adopted to evaluate the clustering quality. The experimental results with the Wilcoxon statistical test demonstrate the superiority of the proposed method in both clustering performance and operational efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2021.3053057DOI Listing
March 2021

Facile design of gemini surfactant-like peptide for hydrophobic drug delivery and antimicrobial activity.

J Colloid Interface Sci 2021 Jun 8;591:314-325. Epub 2021 Feb 8.

Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China; National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Recently, many kinds of gemini-type amphiphilic peptides have been designed and shown their advantage as self-assembling nanomaterials. In this study, we proposed a simple strategy to design gemini surfactant-like peptides, which are only composed of natural amino acids and can be easily obtained by conventional peptide sythnesis. Taking two prolines as the turn-forming units, a peptide named APK was designed. The petide has a linear sequence but naturally takes the conformation like a gemini surfactant. Compared with a single-tailed surfactant-like peptide A6K, APK showed much stronger ability to undergo self-assembly and to encapsulate hydrophobic pyrene. Several hydrophobic drugs including paclitaxel, doxorubicin, etomidate and propofol were encapsulated by APK, and the corresponding formulations showed anti-tumor or anesthetic efficacy comparable to their respective clinical formulations. Furthermore, APK could inhibit the growth of different microorganisms including E. coli, S. aureus and C. albicans. Etomidate and propofol formulations encapsulated by APK also showed strong antimicrobial activity. Taking APK as an example, our study indicated a straightforward strategy to design gemini surfactant-like peptides, which could be potential nanomaterials for exploring hydrophobic drug formulations with efficacy, safety and self-antimicrobial activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.02.019DOI Listing
June 2021

Effective Cancer Subtype and Stage Prediction via Dropfeature-DNNs.

IEEE/ACM Trans Comput Biol Bioinform 2021 Feb 12;PP. Epub 2021 Feb 12.

Precise cancer subtype and/or stage prediction is instrumental for cancer diagnosis, treatment and management. However, most of the existing methods based on genomic profiles suffer from issues such as overfitting, high computational complexity and selected features (i.e., genes) not directly related to forecast precision. These deficiencies are largely due to the nature of "high-dimensionality-small-sample (HDSS)" inherent in molecular data, and such a nature is often deemed as an obstacle to the application of deep learning to biomedical research. In this paper, we propose a DNN-based algorithm coupled with a new embedded feature selection technique, named Dropfeature-DNNs, to address these issues. We formulate Dropfeature-DNNs as an iterative AUC optimization problem when training DNNs. As such, an "optimal" feature subset that contains meaningful genes for patient stratification can be obtained when the AUC optimization converges. Since the feature subset and AUC optimizations are synchronous with the training of DNNs, model complexity and computational cost are simultaneously reduced. Rigorous feature subset convergence analysis and error bound inference provide a solid theoretical foundation for the proposed method. Extensive empirical comparisons to benchmark methods further demonstrate the efficacy of Dropfeature-DNNs in cancer subtype and/or stage prediction using HDSS gene expression data from multiple cancer types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCBB.2021.3058941DOI Listing
February 2021

Mammalian SWI/SNF Chromatin Remodeling Complexes in Embryonic Stem Cells: Regulating the Balance Between Pluripotency and Differentiation.

Front Cell Dev Biol 2020 18;8:626383. Epub 2021 Jan 18.

Cam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.

The unique capability of embryonic stem cells (ESCs) to maintain and adjust the equilibrium between self-renewal and multi-lineage cellular differentiation contributes indispensably to the integrity of all developmental processes, leading to the advent of an organism in its adult form. The ESC fate decision to favor self-renewal or differentiation into specific cellular lineages largely depends on transcriptome modulations through gene expression regulations. Chromatin remodeling complexes play instrumental roles to promote chromatin structural changes resulting in gene expression changes that are key to the ESC fate choices governing the equilibrium between pluripotency and differentiation. BAF (Brg/Brahma-associated factors) or mammalian SWI/SNF complexes employ energy generated by ATP hydrolysis to change chromatin states, thereby governing the accessibility of transcriptional regulators that ultimately affect transcriptome and cell fate. Interestingly, the requirement of BAF complex in self-renewal and differentiation of ESCs has been recently shown by genetic studies through gene expression modulations of various BAF components in ESCs, although the precise molecular mechanisms by which BAF complex influences ESC fate choice remain largely underexplored. This review surveys these recent progresses of BAF complex on ESC functions, with a focus on its role of conditioning the pluripotency and differentiation balance of ESCs. A discussion of the mechanistic bases underlying the genetic requirements for BAF in ESC biology as well as the outcomes of its interplays with key transcription factors or other chromatin remodelers in ESCs will be highlighted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.626383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848206PMC
January 2021

Palladium-modified cuprous(i) oxide with {100} facets for photocatalytic CO reduction.

Nanoscale 2021 Feb 3;13(5):2883-2890. Epub 2021 Feb 3.

School of Civil Engineering c/o Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, P. R. China.

Using metal as a photohole capturer can promote the photoelectron of p-type copper(i) oxide (CuO) substrate for efficient carbon dioxide reduction. However, palladium-decorated CuO (CuO-Pd) is seldom reported due to their mismatching band arrangement. Herein, we have successfully established a matched band alignment between Pd nanoparticles and CuO with exposed {100} facets (100CuO). The high work function of 100CuO originating from T symmetry vibration facilitates the photohole transferring to Pd nanoparticles, which leads to a three-fold increase in the photocatalytic generation of carbon monoxide (100CuO-0.1Pd, 0.13 μmol g h) than that with pristine 100CuO (0.04 μmol g h). Besides, the incorporation of Pd can relieve the photocorrosion of 100CuO, thus promoting its photocatalytic stability. As a contrast, 111CuO (CuO exposed to {111} facets) with low-work function was also synthesized and no charge migration was observed between 111CuO and Pd species, which verified the important role of the crystal surface regulation. All experimental phenomena were certified by the crystal surface analysis and energy band structure construction. Moreover, CO adsorption capacity tests indicated that the incorporation of Pd is beneficial for the capture of CO molecules. We hope that this work to some extent will enrich the subject of photocatalytic CO reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr07703hDOI Listing
February 2021

Quaternary Lidocaine Derivatives: Past, Present, and Future.

Drug Des Devel Ther 2021 14;15:195-207. Epub 2021 Jan 14.

Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Local anesthetics have the advantage of complete analgesia with fewer side effects compared to systemic analgesics. However, their clinical use is limited due to their short duration of action. Thus, local anesthetics with fast onset, long duration of action, selective nociceptive block, and low local and systemic toxicity are highly desirable. In the past electrophysiological studies, quaternary lidocaine derivatives (QLDs) showed these characteristics. Here, we review electrophysiological properties of QLDs and their pharmacodynamic characteristics to shed light on potential problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S291229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813469PMC
September 2021

Genome-wide Interrogation of Protein-DNA Interactions in Mammalian Cells Using ChIPmentation.

STAR Protoc 2020 Dec 4;1(3):100187. Epub 2020 Dec 4.

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

Mapping the genomic locations of chromatin-associated proteins, such as transcription factors and histone modifications, is key to understanding the mechanisms of transcriptional regulation. ChIPmentation offers a simple and robust way of investigating the genomic binding sites of a protein using relatively low-input material. Here, we present a detailed protocol for the key steps that lead to a successful ChIPmentation experiment, as well as a quick analysis pipeline to examine the data. For complete details on the use and execution of this protocol, please refer to Schmidl et al. (2015). For example data produced by this protocol, please refer to Henriksson et al. (2019) and Zhang et al. (2019).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xpro.2020.100187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757419PMC
December 2020

Handwashing Sink Contamination and Carbapenem-resistant Klebsiella Infection in the Intensive Care Unit: A Prospective Multicenter Study.

Clin Infect Dis 2020 12;71(Suppl 4):S379-S385

Department of Infection Control, West China Hospital, Sichuan University, Chengdu, China.

Background: Handwashing sinks can become contaminated by carbapenem-resistant Klebsiella (CRK), including carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Klebsiella oxytoca (CRKO), but whether they are major sources of CRK infections remains unknown.

Methods: We performed a prospective multicenter study in 16 intensive care units (ICUs) (9 general and 7 neonatal) at 11 hospitals. All sinks at these locations were sampled to screen CRK. All CRK clinical isolates recovered between 2 weeks before and 3 months after sampling in ICUs with CRK-positive sinks or other participating ICUs at the same hospital were collected. Whole-genome sequencing of all isolates was performed. Isolates of the same sequence type (ST) were assigned to clones by calling single-nucleotide polymorphisms.

Results: Among 158 sinks sampled, 6 CRKP and 6 CRKO were recovered from 12 sinks in 7 ICUs, corresponding to a 7.6% CRK contamination rate. Twenty-eight clinical isolates were collected, and all were CRKP. The 34 CRKP isolates belonged to 7 STs, including ST789 (n = 14, all had blaNDM-5); ST11 (n = 12, 5 belonged to KL64 and 7 to KL47, all had blaKPC-2); ST709 (n = 4, all had blaNDM-5); and ST16, ST20, ST1027, and ST2407 (n = 1 each). One particular ST789 clone caused an outbreak and contaminated a sink. ST11_KL47 sink isolates were likely the source of a cluster of clinical isolates. Two ST11_KL64 isolates belonged to a common clone but were from 2 hospitals.

Conclusions: Contaminated sinks were not the major source of CRK in our local settings. ST789 blaNDM-5-carrying CRKP might represent an emerging lineage causing neonatal infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1515DOI Listing
December 2020

The 14-day repeated-dose toxicity study of a fixed-dose combination, QXOH/levobupivacaine, via subcutaneous injection in beagle dogs.

J Appl Toxicol 2021 08 12;41(8):1241-1261. Epub 2020 Nov 12.

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jat.4111DOI Listing
August 2021

Domain Adaptation by Class Centroid Matching and Local Manifold Self-Learning.

IEEE Trans Image Process 2020 28;29:9703-9718. Epub 2020 Oct 28.

Domain adaptation has been a fundamental technology for transferring knowledge from a source domain to a target domain. The key issue of domain adaptation is how to reduce the distribution discrepancy between two domains in a proper way such that they can be treated indifferently for learning. In this paper, we propose a novel domain adaptation approach, which can thoroughly explore the data distribution structure of target domain. Specifically, we regard the samples within the same cluster in target domain as a whole rather than individuals and assigns pseudo-labels to the target cluster by class centroid matching. Besides, to exploit the manifold structure information of target data more thoroughly, we further introduce a local manifold self-learning strategy into our proposal to adaptively capture the inherent local connectivity of target samples. An efficient iterative optimization algorithm is designed to solve the objective function of our proposal with theoretical convergence guarantee. In addition to unsupervised domain adaptation, we further extend our method to the semi-supervised scenario including both homogeneous and heterogeneous settings in a direct but elegant way. Extensive experiments on seven benchmark datasets validate the significant superiority of our proposal in both unsupervised and semi-supervised manners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2020.3031220DOI Listing
October 2020
-->