Publications by authors named "Feng Yang"

1,663 Publications

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The potential risk of antibiotic resistance of Streptococcus iniae in sturgeon cultivation in Sichuan, China.

Environ Sci Pollut Res Int 2021 Jul 21. Epub 2021 Jul 21.

College of Veterinary Medicine, Sichuan Agricultural University, Huimin Road No. 211, Wenjiang, Chengdu, Sichuan, 611130, People's Republic of China.

Sichuan, located in the upper reaches of the Yangtze River, is the gathering place of many rivers and plays an important role in sturgeon aquaculture and wild sturgeon protection in China, where it suffered the severe influence of Streptococcus iniae infection in sturgeon. However, the annual thousands of tons of antibiotic usage in Sichuan may accumulate in water and cause obstacles to the prevention of S. iniae infection. In contrast, the regional antibiotic resistance characteristics have been rarely unknown. Seventeen S. iniae strains were collected from the major sturgeon culture areas in Sichuan, and the genotyping and the distribution of antibiotic resistance profiles (ARPs) and genes (ARGs) of S. iniae were established in this study. The results showed that the isolates could be divided into four subtypes by pulsed-field gel electrophoresis analysis. Besides, most isolates showed multiple resistance to the antibiotic such as amikacin, neomycin, enrofloxacin, lincomycin, and sulfamethoxazole. Also, sturgeon-derived S. iniae has a relatively low similarity with other fish-derived S. iniae in the world but high similarity with three animal-derived pathogens from Sichuan in previous studies. Moreover, a total of 37 ARGs were detected positively based on 95 ARGs detection, in which aac(6')-Ib(aka aacA4)-01, aac(6')-Ib(aka aacA4)-02, aadA1, floR, blaTEM, sulA/folP-03, and tetA-02 were most prevalent. Our study indicated that the ARGs of sturgeon-derived S. iniae were significantly enhanced compared with the ATCC29178 strains and have a risk of accessing more ARGs from other bacteria in water in Sichuan. This study claimed that sturgeon has a potential risk in the prevention and control of Streptococcosis in Sichuan, the upper reaches of Yangtze River, based on the antibiotic resistance analysis of S. iniae, and it may also increase the risk of highly resistant S. iniae transmission into the middle and lower reaches.
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http://dx.doi.org/10.1007/s11356-021-15501-1DOI Listing
July 2021

Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.

J Biol Chem 2021 Jul 14:100966. Epub 2021 Jul 14.

Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada M5G 0A4; Department of Biochemistry, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8. Electronic address:

CD22 belongs to the sialic acid-binding immunoglobulin-like lectins (Siglecs) family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B cell receptor due to its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function makes it an attractive target for B-cell depletion in cases of B-cell malignancies. Genetically modified T cells with chimeric antigen receptors (CARs) derived from the m971 antibody have shown promise when used as an immunotherapeutic agent against B-cell acute lymphoblastic leukemia (B-ALL). A key aspect of the efficacy of this CAR-T was its ability to target a membrane-proximal epitope on the CD22 extracellular domain; however, the molecular details of m971 recognition of CD22 have thus far remained elusive. Here, we report the crystal structure of the m971 antigen-binding fragment (Fab) in complex with the two most membrane-proximal immunoglobulin-like domains of CD22 (CD22d6-d7). The m971 epitope on CD22 resides at the most proximal Ig domain (d7) to the membrane, and the antibody paratope contains electrostatic surfaces compatible with interactions with phospholipid head groups. Together, our data identify molecular details underlying the successful transformation of an antibody epitope on CD22 into an effective CAR immunotherapeutic target.
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http://dx.doi.org/10.1016/j.jbc.2021.100966DOI Listing
July 2021

Better Compression with Deep Pre-Editing.

IEEE Trans Image Process 2021 Jul 15;PP. Epub 2021 Jul 15.

Could we compress images via standard codecs while avoiding visible artifacts? The answer is obvious - this is doable as long as the bit budget is generous enough. What if the allocated bit-rate for compression is insufficient? Then unfortunately, artifacts are a fact of life. Many attempts were made over the years to fight this phenomenon, with various degrees of success. In this work we aim to break the unholy connection between bit-rate and image quality, and propose a way to circumvent compression artifacts by pre-editing the incoming image and modifying its content to fit the given bits. We design this editing operation as a learned convolutional neural network, and formulate an optimization problem for its training. Our loss takes into account a proximity between the original image and the edited one, a bit-budget penalty over the proposed image, and a no-reference image quality measure for forcing the outcome to be visually pleasing. The proposed approach is demonstrated on the popular JPEG compression, showing savings in bits and/or improvements in visual quality, obtained with intricate editing effects.
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http://dx.doi.org/10.1109/TIP.2021.3096085DOI Listing
July 2021

The ratio of the posterior atlanto-occipital interval (PAOI): a novel radiographic ratio method evaluating the risk of cervical spondylotic myelopathy-a case-control study.

Quant Imaging Med Surg 2021 Jul;11(7):3018-3028

Orthopedics Department, China-Japan Friendship Hospital, Beijing, China.

Background: Our study aims to introduce a dynamic interval ratio method calculated using cervical hyperextension-flexion X-ray films. Secondarily, we aim to evaluate the relationship between the posterior atlanto-occipital interval ratio and cervical spondylotic myelopathy and explain the rationale.

Methods: We reviewed 83 cases with visible cervical dynamic X-ray films in our hospital from February 2015 to December 2018. Cases were divided into 2 groups according to their diagnosis (with or without spondylotic myelopathy). Radiographic measurements included the shortest distance between the posterior arch of the atlas and the occipital bone and cervical range of motion, and demographic data such as gender, age, and body mass index were also extracted. The posterior atlanto-occipital interval ratio (distance at hyperextension position/distance at hyperflexion position) was determined using logistic regression analysis models between the 2 groups.

Results: We included 40 cases in the disease group and 43 cases in the control group. The mean posterior atlanto-occipital interval ratio was 0.65±0.30 (mean ± standard deviation) in the disease group and 0.30±0.28 in the control group, with a significant difference (P<0.01). There was no correlation between the posterior atlanto-occipital interval ratio and gender or body mass index. However, the interval ratio had strong correlations with age, cervical spondylotic myelopathy, and Japanese Orthopaedic Association scores. Age, posterior atlanto-occipital interval ratio, and interval distance at hyperextension in the disease group were higher than those of the control group. Contrastingly, range of motion, Japanese Orthopaedic Association scores, and interval distance at the disease group's hyperflexion position were lower than in the control group. In all cases, the risk of cervical spondylotic myelopathy in the T2 group (cases with middle posterior atlanto-occipital interval ratio, according to the tertiles) was 6 times more than the T1 group (cases with lower ratio), and the T3 group (cases with higher ratio) had a 26.4 times greater risk than the T1 group.

Conclusions: Our results suggest that the posterior atlanto-occipital interval ratio is a simple and meaningful parameter that could provide prognostic value for the risk of cervical spondylotic myelopathy through the imaging examinations of the selected cases. Higher posterior atlanto-occipital interval ratios indicate a greater risk for cervical spondylotic myelopathy and cervical musculoskeletal dysfunction. A higher posterior atlanto-occipital interval ratio may manifest undetected posterior atlanto-occipital stiffness, which needs more pathological evidence in future studies.
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http://dx.doi.org/10.21037/qims-20-986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249999PMC
July 2021

Sound Effects on Physiological State and Behavior of Drivers in a Highway Tunnel.

Front Psychol 2021 23;12:693005. Epub 2021 Jun 23.

Department of Civil and Architectural Engineering and Construction Management, University of Cincinnati, Cincinnati, OH, United States.

Driving behavior in a highway tunnel could be affected by external environmental factors like light, traffic flow, and acoustic environments, significantly when these factors suddenly change at the moment before and after entering a tunnel. It will cause tremendous physiological pressure on drivers because of the reduction of information and the narrow environment. The risks in driving behavior will increase, making drivers more vulnerable than driving on the regular highways. This research focuses on the usually neglected acoustic environment and its effect on drivers' physiological state and driving behavior. Based on the SIMLAB driving simulation platform of a highway tunnel, 45 drivers participated in the experiment. Five different sound scenarios were tested: original highway tunnel sound and a mix of it with four other sounds (slow music, fast music, voice prompt, and siren, respectively). The subjects' physiological state and driving behavior data were collected through heart rate variability (HRV) and electroencephalography (EEG). Also, vehicle operational data, including vehicle speed, steering wheel angle, brake pedal depth, and accelerator pedal depth, were collected. The results indicated that different sound scenarios in the highway tunnel showed significant differences in vehicle speed ( = 0.000, η = 0.167) and steering wheel angle ( = 0.007, η = 0.126). At the same time, they had no significant difference in HRV and EEG indicators. According to the results, slow music was the best kind of sound related to driving comfort, while the siren sound produced the strongest driver reaction in terms of mental alertness and stress level. The voice-prompt sound most likely caused driver fatigue and overload, but it was the most effective sound affecting safety. The subjective opinion of the drivers indicated that the best sound scenario for the overall experience was slow music (63%), followed by fast music (21%), original highway tunnel sound environment (13%), and voice-prompt sound (3%). The findings of this study will be valuable in improving acoustic environment quality and driving safety in highway tunnels.
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http://dx.doi.org/10.3389/fpsyg.2021.693005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260679PMC
June 2021

Regional gray matter volume associated with exercise dependence: A voxel-based morphometry study.

Hum Brain Mapp 2021 Jul 8. Epub 2021 Jul 8.

Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.

Although regular physical exercise has multiple positive benefits for the general population, excessive exercise may lead to exercise dependence (EXD), which is harmful to one's physical and mental health. Increasing evidence suggests that stress is a potential risk factor for the onset and development of EXD. However, little is known about the neural substrates of EXD and the underlying neuropsychological mechanism by which stress affects EXD. Herein, we investigate these issues in 86 individuals who exercise regularly by estimating their cortical gray matter volume (GMV) utilizing a voxel-based morphometry method based on structural magnetic resonance imaging. Whole-brain correlation analyses and prediction analyses showed negative relationships between EXD and GMV of the right orbitofrontal cortex (OFC), left subgenual cingulate gyrus (sgCG), and left inferior parietal lobe (IPL). Furthermore, mediation analyses found that the GMV of the right OFC was an important mediator between stress and EXD. Importantly, these results remained significant even when adjusting for sex, age, body mass index, family socioeconomic status, general intelligence and total intracranial volume, as well as depression and anxiety. Collectively, the results of the present study provide crucial evidence of the neuroanatomical basis of EXD and reveal a potential neuropsychological pathway in predicting EXD in which GMV mediates the relationship between stress and EXD.
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http://dx.doi.org/10.1002/hbm.25585DOI Listing
July 2021

The New Is Old: Novel Germination Strategy Evolved From Standing Genetic Variation in Weedy Rice.

Front Plant Sci 2021 21;12:699464. Epub 2021 Jun 21.

National Observations and Research Station for Wetland Ecosystems of the Yangtze Estuary, Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Fudan University, Shanghai, China.

Feralization of crop plants has aroused an increasing interest in recent years, not only for the reduced yield and quality of crop production caused by feral plants but also for the rapid evolution of novel traits that facilitate the evolution and persistence of weedy forms. Weedy rice ( f. ) is a conspecific weed of cultivated rice, with separate and independent origins. The weedy rice distributed in eastern and northeastern China did not diverge from their cultivated ancestors by reverting to the pre-domestication trait of seed dormancy during feralization. Instead, they developed a temperature-sensing mechanism to control the timing of seed germination. Subsequent divergence in the minimum critical temperature for germination has been detected between northeastern and eastern populations. An integrative analysis was conducted using combinations of phenotypic, genomic and transcriptomic data to investigate the genetic mechanism underlying local adaptation and feralization. A dozen genes were identified, which showed extreme allele frequency differences between eastern and northeastern populations, and high correlations between allele-specific gene expression and feral phenotypes. Trancing the origin of potential adaptive alleles based on genomic sequences revealed the presence of most selected alleles in wild and cultivated rice genomes, indicating that weedy rice drew upon pre-existing, "conditionally neutral" alleles to respond to the feral selection regimes. The cryptic phenotype was exposed by activating formerly silent alleles to facilitate the transition from cultivation to wild existence, promoting the evolution and persistence of weedy forms.
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http://dx.doi.org/10.3389/fpls.2021.699464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256273PMC
June 2021

Improving maize's N uptake and N use efficiency by strengthening roots' absorption capacity when intercropped with legumes.

PeerJ 2021 23;9:e11658. Epub 2021 Jun 23.

College of Agronomy, Sichuan Agricultural University, Chengdu, China.

Maize's nitrogen (N) uptake can be improved through maize-legume intercropping. N uptake mechanisms require further study to better understand how legumes affect root growth and to determine maize's absorptive capacity in maize-legume intercropping. We conducted a two-year field experiment with two N treatments (zero N (N0) and conventional N (N1)) and three planting patterns (monoculture maize ( L.) (MM), maize-soybean ( L. .) strip intercropping (IMS), and maize-peanut ( L.) strip intercropping (IMP)). We sought to understand maize's N uptake mechanisms by investigating root growth and distribution, root uptake capacity, antioxidant enzyme activity, and the antioxidant content in different maize-legume strip intercropping systems. Our results showed that on average, the N uptake of maize was significantly greater by 52.5% in IMS and by 62.4% in IMP than that in MM. The average agronomic efficiency (AE) of maize was increased by 110.5 % in IMS and by 163.4 % in IMP, compared to MM. The apparent recovery efficiency (RE) of maize was increased by 22.3% in IMS. The roots of intercropped maize were extended into soybean and peanut stands underneath the space and even between the inter-rows of legume, resulting in significantly increased root surface area density (RSAD) and total root biomass. The root-bleeding sap intensity of maize was significantly increased by 22.7-49.3% in IMS and 37.9-66.7% in IMP, compared with the MM. The nitrate-N content of maize bleeding sap was significantly greater in IMS and IMP than in MM during the 2018 crop season. The glutathione (GSH) content, superoxide dismutase (SOD), and catalase (CAT) activities in the root significantly increased in IMS and IMP compared to MM. Strip intercropping using legumes increases maize's aboveground N uptake by promoting root growth and spatial distribution, delaying root senescence, and strengthening root uptake capacity.
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http://dx.doi.org/10.7717/peerj.11658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234926PMC
June 2021

The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.

Signal Transduct Target Ther 2021 Jul 5;6(1):249. Epub 2021 Jul 5.

Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai, China.

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.
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http://dx.doi.org/10.1038/s41392-021-00659-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255319PMC
July 2021

[Recent advance of new sample preparation materials in the analysis and detection of environmental pollutants].

Se Pu 2021 Aug;39(8):781-801

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China.

To successfully analyze complex samples and detect trace targets, sample pretreatment is essential. Efficient sample pretreatment techniques can remove or reduce interference from the sample matrix. It can also enrich analytes, thereby improving analytical accuracy and sensitivity. In recent years, various sample preparation techniques, including SPE, magnetic dispersion SPE, pipette tip SPE, stir bar extraction, fiber SPME, and in-tube SPME, have received increasing attention in environmental analysis and monitoring. The extraction efficiency mainly depends on the type of adsorbent material. Therefore, the development of efficient adsorbents is a crucial step toward sample preparation. This review summarizes and discusses the research advances in extraction materials over recent years. These extraction materials contain inorganic adsorbents, organic adsorbents, and inorganic-organic hybrid materials such as graphene, graphene oxide, carbon nanotubes, inorganic aerogels, organic aerogels, triazinyl-functionalized materials, triazine-based polymers, molecularly imprinted polymers, covalent organic frameworks, metal-organic frameworks, and their derivatives. These materials have been applied to extract different types of pollutants, including metal ions, polycyclic aromatic hydrocarbons, plasticizers, alkanes, phenols, chlorophenols, chlorobenzenes, polybrominated diphenyl ethers, perfluorosulfonic acids, perfluorocarboxylic acids, estrogens, drug residues, and pesticide residues, from environmental samples (such as water and soil samples). These sample preparation materials possess high surface areas, numerous adsorption sites, and allow extraction via various mechanisms, such as , electrostatic, hydrophobic, and hydrophilic interactions, as well as hydrogen and halogen bond formation. Various sample pretreatment techniques based on these extraction materials have been combined with various detection methods, including chromatography, mass spectrometry, atomic absorption spectroscopy, fluorescence spectroscopy, and ion mobility spectroscopy, and have been extensively used for the determination of environmental pollutants. The existing challenges associated with the development of sample preparation techniques are proposed, and prospects for such extraction materials in environmental analysis and monitoring are discussed. Major trends in the field, including the development of efficient extraction materials with high enrichment ability, good selectivity, excellent thermal stability, and chemical stability, are discussed. Green sample pretreatment materials, environmentally friendly synthesis methods, and green sample pretreatment methods are also explored. Rapid sample pretreatment methods that can be conducted within minutes or seconds are of significant interest. Further, online sample pretreatment and automatic analysis methods have attracted increasing attention. Besides, real-time analysis and in situ detection have been important development directions, and are expected to be widely applicable in environmental analysis, biological detection, and other fields. Modern synthesis technology should be introduced to synthesize specific extraction materials. Controllable preparation methods for extraction materials, such as the in situ growth or in situ preparation of extraction coatings, will acquire importance in coming years. It will also be important to adopt high-performance materials from other fields for sample pretreatment. Organic-inorganic hybrid extraction materials can combine the advantages both organic materials and inorganic materials, and mutually compensate for any disadvantages. Extraction materials doped with nanomaterials are also promising. Although existing sample pretreatment techniques are relatively efficient, it is still imperative to develop novel sample preparation methods.
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http://dx.doi.org/10.3724/SP.J.1123.2021.02030DOI Listing
August 2021

Knee joint biomechanics of simplified 24 Tai Chi forms and association with pain in individuals with knee osteoarthritis: A pilot study.

Authors:
Feng Yang Wei Liu

Osteoarthr Cartil Open 2021 Jun 6;3(2). Epub 2021 Mar 6.

School of Health Professions, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.

Objectives: Tai Chi (TC) is a multi-beneficial exercise for improving health and function in knee osteoarthritis (OA). Biomechanical insights of 24 TC forms at the knee joint are not well understood. We aimed to examine knee joint biomechanics of TC actions form by form and their interactions with pain in individuals with knee OA.

Methods: Ten knee OA participants were recruited. Their full body motion during performance of 24 TC forms was collected. The knee joint biomechanics were determined by using an inverse dynamic approach based on collected full body kinematics and kinetics. In addition, the knee joint pain level was scored during each TC form. The joint moments were compared between walking trials and each TC form. The relationship between knee joint biomechanics and pain scale was assessed.

Results: The knee adduction moment for five TC forms was different from the walking trial. The knee extension moment for 21 TC forms differed from the walking trial. For TC trials, the knee extension moment, but not the adduction moment, was positively correlated with pain level. Similarly, the knee extension moment was moderately proportional to pain level during the walking trials, but not the adduction moment.

Conclusions: Our pilot results explored the knee joint biomechanics profiles of individual TC forms and examined their associations with knee joint pain. The findings in this study could provide scientific basis to select the best TC forms for the purpose of reducing knee joint pain among individuals with knee OA.
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http://dx.doi.org/10.1016/j.ocarto.2021.100149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245205PMC
June 2021

Abnormal spatiotemporal expression pattern of progranulin and neurodevelopment impairment in VPA-induced ASD rat model.

Neuropharmacology 2021 Jun 25;196:108689. Epub 2021 Jun 25.

Cerebrovascular Diseases Laboratory, Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Some environmental risk factors have been proven to contribute to the etiology of autism spectrum disorder (ASD). Exposure to the antiepileptic drug valproic acid (VPA) during pregnancy significantly increases the risk of ASD in humans, and consequently is utilized as a validated animal model of ASD in rodents; however, the precise molecular and cellular mechanisms remain ill-defined. In the present study, we investigated the effect of prenatal VPA exposure on the spatiotemporal dynamics of Progranulin (PGRN) expression, neuronal apoptosis, synapse density, and AKT/GSK-3β pathway activation in the brains of VPA-exposed offspring. Results from behavioral tests were consistent with prior studies showing impaired sociability, restricted interests and increased repetitive behaviors in VPA rats at postnatal days 28-32. Our data also indicated that VPA exposure resulted in abnormal dynamics of PGRN expression in different brain regions at the different development stages. The temporal and spatial patterns of PGRN expression were consistent with the spatiotemporal regularity of abnormalities, which observed in apoptosis-related protein levels, neuron numbers, dendritic spine density, synapse-related protein levels, and AKT/GSK-3β phosphorylation in VPA rats. It suggests that prenatal VPA exposure may affect the spatiotemporal regularity of neuronal apoptosis and synaptic development/regression via interfering with the spatiotemporal process of PGRN expression and downstream AKT/GSK-3β pathway activation. This may be a potential mechanism of the abnormal neuroanatomical changes and ASD-like behaviors in VPA-induced ASD.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108689DOI Listing
June 2021

Crayfish hemocytes develop along the granular cell lineage.

Sci Rep 2021 Jun 23;11(1):13099. Epub 2021 Jun 23.

Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184# Daxue Road, Xiamen, 361005, China.

Despite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.
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http://dx.doi.org/10.1038/s41598-021-92473-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222279PMC
June 2021

Use of the rhizobial type III effector gene nopP to improve Agrobacterium rhizogenes-mediated transformation of Lotus japonicus.

Plant Methods 2021 Jun 23;17(1):66. Epub 2021 Jun 23.

State Key Laboratory of Biocontrol and Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-Sen University, East Campus, Guangzhou, 510006, China.

Background: Protocols for Agrobacterium rhizogenes-mediated hairy root transformation of the model legume Lotus japonicus have been established previously. However, little efforts were made in the past to quantify and improve the transformation efficiency. Here, we asked whether effectors (nodulation outer proteins) of the nodule bacterium Sinorhizobium sp. NGR234 can promote hairy root transformation of L. japonicus. The co-expressed red fluorescent protein DsRed1 was used for visualization of transformed roots and for estimation of the transformation efficiency.

Results: Strong induction of hairy root formation was observed when A. rhizogenes strain LBA9402 was used for L. japonicus transformation. Expression of the effector gene nopP in L. japonicus roots resulted in a significantly increased transformation efficiency while nopL, nopM, and nopT did not show such an effect. In nopP expressing plants, more than 65% of the formed hairy roots were transgenic as analyzed by red fluorescence emitted by co-transformed DsRed1. A nodulation experiment indicated that nopP expression did not obviously affect the symbiosis between L. japonicus and Mesorhizobium loti.

Conclusion: We have established a novel protocol for hairy root transformation of L. japonicus. The use of A. rhizogenes LBA9402 carrying a binary vector containing DsRed1 and nopP allowed efficient formation and identification of transgenic roots.
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http://dx.doi.org/10.1186/s13007-021-00764-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220826PMC
June 2021

Self-assembled nano-Ag/[email protected] film composite SERS substrates show high uniformity and high enhancement factor for creatinine detection.

Nanotechnology 2021 Jul 9;32(39). Epub 2021 Jul 9.

College of Optoelectronic Engineering, Key Laboratory of Optoelectronic Technology and Systems, Ministry of Education, Key Disciplines Lab of Novel Micro-Nano Devices and System Technology, Chongqing University, Chongqing 400044, People's Republic of China.

Serum creatinine is a key biomarker for the diagnosis and monitoring of kidney disease. Rapid and sensitive creatinine detection is thus important. Here, we propose a high-performance nano-Ag/[email protected] film composite SERS substrate for the rapid detection of creatinine in human serum. Au nanoparticles (AuNPs) and Ag nanoparticles (AgNPs) with uniform particle size were synthesized by a chemical reduction method, and the nano-Ag/[email protected] film composite SERS substrate was successfully prepared via a consecutive layer-on-layer deposition using an optimized liquid-liquid interface self-assembly method. The finite element simulation analysis showed that due to the multi-dimensional plasmonic coupling effect formed between the AuNPs, AgNPs, and the Au film, the intensity of the local electromagnetic field was greatly improved, and a very high enhancement factor (EF) was obtained. Experimental results showed that the limit of detection (LOD) of this composite SERS substrate for rhodamine 6G (R6G) molecules was as low as 1 × 10M, and the Raman EF was 15.7 and 2.9 times that of the AuNP and AgNP monolayer substrates respectively. The results of different batch tests and SERS mapping showed that the relative standard deviations of the Raman intensity of R6G at 612 cmwere 12.5% and 11.7%, respectively. Finally, we used the SERS substrate for the label-free detection of human serum creatinine. The results showed that the LOD of this SERS substrate for serum creatinine was 5 × 10M with a linear correlation coefficient of 0.96. In conclusion, the SERS substrate has high sensitivity, good uniformity, simple preparation, and has important developmental potential for the rapid detection and application of disease biomarkers.
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http://dx.doi.org/10.1088/1361-6528/ac0dddDOI Listing
July 2021

Theoretical Study of Effects of Solvents, Ligands, and Anions on Separation of Trivalent Lanthanides and Actinides.

Inorg Chem 2021 Jul 23;60(13):9552-9562. Epub 2021 Jun 23.

School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Due to its associated low CO emissions, nuclear energy production is rapidly growing. In this context, the treatment of high-level liquid waste (HLLW) of nuclear plants is of high concern to both scientific and industrial communities. Specifically, the separation of An(III) and Ln(III) cations when processing nuclear fuel is a vitally important, yet challenging, step within HLLW because An(III) and Ln(III) have similar chemical properties in solution. To guide the choice of relevant ligands, anions, and solvents for this separation step, in this work, we calculate and compare the free energy of formation of different Am(III) and Eu(III) complexes (which are typical and important An(III) and Ln(III) cation examples), involving two different ligands and three different counter ions in four different solvents. Based on our calculations, we predict that the chosen solvent is a key factor in the extraction of Am(III) and Eu(III) in treatment of HLLW. This study supports a systematic, computation-assisted screening of solvents and extractive ligands with counter anions as a proficient method to optimize the separation of Ln(III) and An(III).
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http://dx.doi.org/10.1021/acs.inorgchem.1c00657DOI Listing
July 2021

Multifactorial Mechanisms of Tolerance to Ketoconazole in Candida albicans.

Microbiol Spectr 2021 Jun 23:e0032121. Epub 2021 Jun 23.

Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Candida albicans is a prevalent opportunistic human fungal pathogen for which treatment is limited to only four main classes of antifungal drugs, with the azole and echinocandin classes being used most frequently. Drug tolerance, the ability of some cells to grow slowly in supra-MIC drug concentrations, decreases the number of available treatment options. Here, we investigated factors affecting tolerance and resistance to ketoconazole in C. albicans. We found both temperature and the composition of growth medium significantly affected tolerance with little effect on resistance. In deletion analysis of known efflux pump genes, was partially required for azole tolerance, while and were dispensable. Tolerance also required Hsp90 and calcineurin components; , which encodes a transcription factor downstream of calcineurin, was required only partially. Deletion of , which encodes a vacuolar ATPase subunit, and concanamycin A, a V-ATPase inhibitor, abolished tolerance, indicating the importance of vacuolar energy transactions in tolerance. Thus, tolerance to ketoconazole is regulated by multiple factors, including physiological and genetic mechanisms. Due to the ever-expanding range of invasive medical procedures and treatments, invasive fungal infections now pose a serious global threat to many people living in an immunocompromised status. Like humans, fungi are eukaryotic, which significantly limits the number of unique antifungal targets; the current arsenal of antifungal agents is limited to just three frontline drug classes. Additional treatment complexities result from the development of drug tolerance and resistance, which further narrows therapeutic options; however, the difference between tolerance and resistance remains largely unknown. This study demonstrates that tolerance and resistance are regulated by multiple genetic and physiological factors. It is prudent to note that some factors affect tolerance only, while other factors affect both tolerance and resistance. The complex underlying mechanisms of these drug responses are highlighted by the fact that there are both shared and distinct mechanisms that regulate tolerance and resistance.
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http://dx.doi.org/10.1128/Spectrum.00321-21DOI Listing
June 2021

A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling.

Front Cardiovasc Med 2021 2;8:677727. Epub 2021 Jun 2.

Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.

Heart failure is induced by multiple pathological mechanisms, and current therapies are ineffective against heart failure with preserved ejection fraction (HFpEF). As there are limited animal models of HFpEF, its underlying mechanisms have not yet been elucidated. Here, we employed the descending aortic constriction (DAC) technique to induce chronic pressure overload in the left ventricles of Tibetan minipigs for 12 weeks. Cardiac function, pathological and cellular changes, fibrotic signaling activation, and gene expression profiles were explored. The left ventricles developed concentric hypertrophy from weeks 4 to 6 and transition to dilation starting in week 10. Notably, the left ventricular ejection fraction was maintained at >50% in the DAC group during the 12-week period. Pathological examination, biochemical analyses, and gene profile analysis revealed evidence of inflammation, fibrosis, cell death, and myofilament dephosphorylation in the myocardium of HFpEF model animals, together with gene expression shifts promoting cardiac remodeling and downregulating metabolic pathways. Furthermore, we noted the activation of several signaling proteins that impact cardiac fibrosis and remodeling, including transforming growth factor-β/SMAD family members 2/3, type I/III/V collagens, phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases 1 and 2, interleukins 6 and 1β, and inhibitor of κBα/nuclear factor-κB. Our findings demonstrate that this chronic pressure overload-induced porcine HFpEF model is a powerful tool to elucidate the mechanisms of this disease and translate preclinical findings.
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http://dx.doi.org/10.3389/fcvm.2021.677727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206269PMC
June 2021

A Photosensitive Polymeric Carrier with a Renewable Singlet Oxygen Reservoir Regulated by Two NIR Beams for Enhanced Antitumor Phototherapy.

Small 2021 Jul 18;17(29):e2101180. Epub 2021 Jun 18.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Key Laboratory of Functional Polymer Materials of Ministry of Education, Nankai University, Tianjin, 300071, P. R. China.

Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen ( O ) upon laser irradiation to ablate tumors, will exacerbate the already oxygen shortage of most solid tumors and is thus self-limiting. Herein, a sophisticated photosensitive polymeric material (An-NP) that allows sustained O generation and sufficient oxygen supply during the entire phototherapy is engineered by alternatively applying PDT and photothermal therapy (PTT) controlled by two NIR laser beams. In addition to a photosensitizer that generates O , An-NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing O with superior reversibility and a dye J-aggregate with superb photothermal performance. Thus, in 655 nm laser-triggered PDT process, An-NP generates abundant O with extra O being trapped via the conversion into EPO-NP; while in the subsequent 785 nm laser-driven PTT process, the converted EPO-NP undergoes thermolysis to liberate the captured O and regenerates An-NP. The intratumoral oxygen level can be replenished during the PTT cycle for the next round of PDT to generate O . The working principle and phototherapy efficacy are preliminarily demonstrated in living cells and tumor-bearing mice, respectively.
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http://dx.doi.org/10.1002/smll.202101180DOI Listing
July 2021

Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study.

BMC Infect Dis 2021 Jun 19;21(1):587. Epub 2021 Jun 19.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China.

Background: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.

Methods: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.

Results: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8 T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy.

Conclusion: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.
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http://dx.doi.org/10.1186/s12879-021-06255-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214306PMC
June 2021

Polymerized vorinostat mediated photodynamic therapy using lysosomal spatiotemporal synchronized drug release complex.

Colloids Surf B Biointerfaces 2021 Sep 9;205:111903. Epub 2021 Jun 9.

School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China. Electronic address:

A combination of photodynamic therapy (PDT) and histone deacetylase inhibitor (HDACis) could potentiate single-mode anti-tumor activity of HDACis or PDT to inhibit tumor relapse and metastasis. However, poor solubility and heterogeneity in cellular uptake and tissue distribution hamper the dual mode antitumor effect. For a controlled drug release of photosensitizers and HDACis in cytoplasm, photosensitizer pyropheophorbide-a (Pyro) encapsulated in polymer polyethylene glycol-b-poly (asparaginyl-vorinostat) (simplified as [email protected]) are fabricated to achieve their lysosomal spatiotemporal synchronized release. With HDACis modeling PDT in vitro and in vivo, it seems that polymerized Vorinostat encapsulated photosensitizers significantly inhibited the tumor proliferation and metastasis by spatiotemporal synchronized drugs release, and [email protected] reported here reveals a promising prospect to exert drugs' synergistic effect in a spatiotemporal synchronized manner and can be an effective strategy to inhibit tumor growth, recurrence and metastasis in clinic.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111903DOI Listing
September 2021

Speckle-reduced reconstruction of a single-shot hologram by multiple tip-tilt modulations.

Appl Opt 2021 Jun;60(17):5220-5226

Speckle can be attenuated by averaging the reconstructed images of each sub-hologram or being filtered with different filters, at the expense of resolution. We propose a de-speckling method for a single-shot digital hologram while maintaining the resolution. Different tip-tilt phases are demonstrated to cause changes only for the speckle distributions of the reconstructed image. The speckle is attenuated by averaging these intensity images with different speckle distributions. The normalized contrast can be reduced to 0.56 by averaging only 20 different reconstructed images. When the averaged image is processed with block matching and 3D filtering, a further de-speckled image at a normalized contrast of 0.46 can be obtained with highly preserved resolution.
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http://dx.doi.org/10.1364/AO.426329DOI Listing
June 2021

Applications of 2D-Layered Palladium Diselenide and Its van der Waals Heterostructures in Electronics and Optoelectronics.

Nanomicro Lett 2021 Jun 14;13(1):143. Epub 2021 Jun 14.

Institute for Materials Science and Max Bergmann Center of Biomaterials, Technische Universität Dresden, 01069, Dresden, Germany.

The rapid development of two-dimensional (2D) transition-metal dichalcogenides has been possible owing to their special structures and remarkable properties. In particular, palladium diselenide (PdSe) with a novel pentagonal structure and unique physical characteristics have recently attracted extensive research interest. Consequently, tremendous research progress has been achieved regarding the physics, chemistry, and electronics of PdSe. Accordingly, in this review, we recapitulate and summarize the most recent research on PdSe, including its structure, properties, synthesis, and applications. First, a mechanical exfoliation method to obtain PdSe nanosheets is introduced, and large-area synthesis strategies are explained with respect to chemical vapor deposition and metal selenization. Next, the electronic and optoelectronic properties of PdSe and related heterostructures, such as field-effect transistors, photodetectors, sensors, and thermoelectric devices, are discussed. Subsequently, the integration of systems into infrared image sensors on the basis of PdSe van der Waals heterostructures is explored. Finally, future opportunities are highlighted to serve as a general guide for physicists, chemists, materials scientists, and engineers. Therefore, this comprehensive review may shed light on the research conducted by the 2D material community.
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http://dx.doi.org/10.1007/s40820-021-00660-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203759PMC
June 2021

Ultra-strong bio-glue from genetically engineered polypeptides.

Nat Commun 2021 06 14;12(1):3613. Epub 2021 Jun 14.

Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue's robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.
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http://dx.doi.org/10.1038/s41467-021-23117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203747PMC
June 2021

Changing light promotes isoflavone biosynthesis in soybean pods and enhances their resistance to mildew infection.

Plant Cell Environ 2021 Aug 21;44(8):2536-2550. Epub 2021 Jun 21.

Institute of Ecological Agriculture, Sichuan Agricultural University, Chengdu, Sichuan, China.

Mildew severely reduces soybean yield and quality, and pods are the first line of defence against pathogens. Maize-soybean intercropping (MSI) reduces mildew incidence on soybean pods; however, the mechanism remains unclear. Changing light (CL) from maize shading is the most important environmental feature in MSI. We hypothesized that CL affects isoflavone accumulation in soybean pods, affecting their disease resistance. In the present study, shading treatments were applied to soybean plants during different developmental stages according to various CL environments under MSI. Chlorophyll fluorescence imaging (CFI) and classical evaluation methods confirmed that CL, especially vegetative stage shading (VS), enhanced pod resistance to mildew. Further metabolomic analyses and exogenous jasmonic acid (JA) and biosynthesis inhibitor experiments revealed the important relationship between JA and isoflavone biosynthesis, which had a synergistic effect on the enhanced resistance of CL-treated pods to mildew. VS promoted the biosynthesis and accumulation of constitutive isoflavones upstream of the isoflavone pathway, such as aglycones and glycosides, in soybean pods. When mildew infects pods, endogenous JA signalling stimulated the biosynthesis of downstream inducible malonyl isoflavone (MIF) and glyceollin to improve pod resistance.
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http://dx.doi.org/10.1111/pce.14128DOI Listing
August 2021

The effect of targeted psychological nursing intervention on postoperative pain and quality of life in patients with radical mastectomy.

Authors:
Bin Hao Yang Feng

Minerva Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Traumatic Orthopedics, Jinan people's Hospital Affiliated to Shandong First Medical University, Jinan, China.

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http://dx.doi.org/10.23736/S0026-4806.21.07522-4DOI Listing
June 2021

π-Conjugated Macrocycle Host-Guest Coassembly with C60 on HOPG.

Langmuir 2021 Jun 10;37(24):7486-7491. Epub 2021 Jun 10.

CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China.

Two kinds of π-conjugated macrocycles with aggregation-induced emission (AIE) properties were investigated by scanning tunneling microscopy (STM) to elucidate their self-assembly behaviors and interaction with C60 on a highly oriented pyrolytic graphite (HOPG) surface. Both TPEMC and TPEMCS could self-assemble into orderly cavity structures. However, C60 guest molecules could only successfully enter the cavity of TPEMC to form a stable TPEMC + C60 host-guest coassembly structure. Density functional theory (DFT) calculations were also used to interpret the assembly mechanisms. This work disclosed the assembly characteristic of these new types of conjugated macrocyclic compounds, which was helpful to develop new structural porous luminescent materials.
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http://dx.doi.org/10.1021/acs.langmuir.1c00886DOI Listing
June 2021

Host-Guest Molecular Interaction Enabled Separation of Large-Diameter Semiconducting Single-Walled Carbon Nanotubes.

J Am Chem Soc 2021 Jul 9;143(27):10120-10130. Epub 2021 Jun 9.

Beijing National Laboratory for Molecular Science, Key Laboratory for the Physics and Chemistry of Nanodevices, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Semiconducting single-walled carbon nanotubes (s-SWCNTs) with a diameter of around 1.0-1.5 nm, which present bandgaps comparable to silicon, are highly desired for electronic applications. Therefore, the preparation of s-SWCNTs of such diameters has been attracting great attention. The inner surface of SWCNTs has a suitable curvature and large contacting area, which is attractive in host-guest chemistry triggered by electron transfer. Here we reported a strategy of host-guest molecular interaction between SWCNTs and inner clusters with designed size, thus selectively separating s-SWCNTs of expected diameters. When polyoxometalate clusters of ∼1 nm in size were filled in the inner cavities of SWCNTs, s-SWCNTs with diameters concentrated at ∼1.3-1.4 nm were selectively extracted with the purity of ∼98% by a commercially available polyfluorene derivative. The field-effect transistors built from the sorted s-SWCNTs showed a typical behavior of semiconductors. The sorting mechanisms associated with size-dependent electron transfer from nanotubes to inner polyoxometalate were revealed by the spectroscopic and electron microscopic evidence as well as the theoretical calculation. The polyoxometalates with designable size and redox property enable the flexible regulation of interaction between the nanotubes and the clusters, thus tuning the diameter of sorted s-SWCNTs. The present sorting strategy is simple and should be generally feasible in other SWCNT sorting techniques, bringing both great easiness in dispersant design and improved selectivity.
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http://dx.doi.org/10.1021/jacs.1c02245DOI Listing
July 2021

Spontaneous Echo Contrast Mimicking Left Ventricular Thrombus in a Patient on Extracorporeal Membrane Oxygenation Support.

Chest 2021 Jun;159(6):e437-e439

Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1016/j.chest.2020.06.090DOI Listing
June 2021

Potentiation of flutamide-induced hepatotoxicity in mice by Xian-Ling-Gu-Bao through induction of CYP1A2.

J Ethnopharmacol 2021 Oct 4;278:114299. Epub 2021 Jun 4.

Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563003, China. Electronic address:

Ethnopharmacological Relevance: Xian-Ling-Gu-Bao (XLGB) Fufang is herbal formula widely used to treat osteoporosis and other bone disorders. Because of its commonality in the clinical use, there is a safety concern over the use of XLGB combined with other androgen deprivation therapy (ADT) drugs such as flutamide (FLU) that is associated with reduced bone density. To date, there have been no evaluations on the side effects of the drug-drug interaction between XLGB and FLU.

Aim Of The Study: The present study was designed to investigate the hepatotoxicity in the context of the combined treatment of XLGB and FLU in a mouse model, and to determine whether the metabolic activation of FLU through induction of CYP1A2 plays a role in the increased hepatoxicity caused by the combination of XLGB and FLU.

Materials And Methods: C57 mice were administered with either XLGB (6,160 mg/kg), FLU (300 mg/kg), or with the combination of the two drugs. Animals were treated with XLGB for 5 days before the combined administration of XLGB and FLU for another 4 days. The serum of mice from single or the combined administration groups was collected for biochemical analysis. The mouse liver was collected to examine liver morphological changes, evaluate liver coefficient, as well as determine the mRNA expression of P450 isozymes (Cyp1a2, Cyp3a11 and Cyp2c37). For metabolism analysis, mice were treated with XLGB, FLU, or the combination of XLGB and FLU for 24 h. The urine samples were collected for the analysis of FLU-NAC conjugate by UPLC-Q-Orbitrap MS. The liver microsomes were prepared from fresh livers to determine the activity of metabolizing enzyme CYP1A2.

Results: The combined treatment of XLGB and FLU caused loss of mice body weight and elicited significant liver toxicity as evidenced by an increased liver coefficient and serum lactate dehydrogenase (LDH) activity as well as pathological changes of fatty lesion of liver tissue. FLU increased hepatic expression of Cyp1a2 mRNA that was further elevated in the liver of mice when administered with both FLU and XLGB. Treatment of FLU resulted in an increase in the expression of Cyp3a11 mRNA that was negated when mice were co-treated with FLU and XLGB. No significant difference in Cyp2c37 mRNA expression was observed among the different treatment groups as compared to the control. Analysis of metabolic activity showed that the combined administration caused a synergic effect in elevating the activity of the CYP1A2 enzyme. Mass spectrometry analysis identified the presence of FLU reactive metabolite derived FLU-NAC conjugate in the urine of mice treated with FLU. Strikingly, about a two-fold increase of the FLU-NAC conjugate was detected when treated with both FLU and XLGB, indicating an elevated amount of toxic metabolite produced from FLU in the present of XLGB.

Conclusion: FLU and XLGB co-treatment potentiated FLU-induced hepatoxicity. This increased hepatoxicity was mediated through the induction of CYP1A2 activity which in turn enhanced bioactivation of FLU leading to over production of FLU-NAC conjugate and oxidative stress. These results offer warnings about serious side effects of the FLU-XLGB interaction in the clinical practice.
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http://dx.doi.org/10.1016/j.jep.2021.114299DOI Listing
October 2021