Publications by authors named "Chao Wang"

4,553 Publications

  • Page 1 of 1

Effects of a yeast-derived product on growth performance, antioxidant capacity, and immune function of broilers.

Poult Sci 2021 Jun 24;100(9):101343. Epub 2021 Jun 24.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China. Electronic address:

Yeast culture plus enzymatically hydrolyzed yeast cell wall (YC-EHY) contains crude protein, mannan-oligosaccharide, β-glucan and yeast culture. This study was carried out to explore the effects of dietary YC-EHY at different levels on growth performance, antioxidant capacity, and immune function of broiler chickens. A total of 320 one-day-age male broiler chicks were allocated into 4 groups and were fed with a basal diet supplemented with 0 mg/kg (the control group), 50 mg/kg, 100 mg/kg, 150 mg/kg YC-EHY for 42 d. Dietary YC-EHY improved average daily gain and feed efficiency during the starter, grower, and overall periods as well as average body weight of broiler chickens on 42 d (linear and quadratic, P < 0.05). Broiler chickens fed with YC-EHY quadratically increased jejunal sucrase activity on 21 d (quadratic, P < 0.05), and linearly and quadratically enhanced maltase activity on 21 and 42 d (linear and quadratic, P < 0.05). Supplementing YC-EHY linearly and quadratically enhanced jejunal superoxide dismutase (SOD) activity on 21 and 42 d and glutathione peroxidase (GPX) activity on 42 d whereas decreased malonaldehyde (MDA) concentration on 42 d (linear and quadratic, P < 0.05). Consistently, the jejunal genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD1 on 21 and 42 d, heme oxygenase-1 (HO-1) and GPX1 on 42 d were enhanced by YC-EHY supplementation (linear and quadratic, P < 0.05). The concentrations of jejunal immunoglobulin G (IgG) on 21 and 42 d and secreted immunoglobulin A (SIgA) on 42 d were linearly and quadratically elevated by supplementing YC-EHY (linear and quadratic, P < 0.05). Dietary YC-EHY quadratically increased jejunal IgG and IgM genes expression on 21 d (quadratic, P < 0.05), and linearly and quadratically enhanced the genes expression of IgG and IgM on 42 d (linear and quadratic, P < 0.05). Overall, this study indicated that supplementing YC-EHY could exert beneficial effects on growth performance, intestinal antioxidant capacity and immune function in broiler chickens.
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http://dx.doi.org/10.1016/j.psj.2021.101343DOI Listing
June 2021

Anthropogenic disturbances on antibiotic resistome along the Yarlung Tsangpo River on the Tibetan Plateau: Ecological dissemination mechanisms of antibiotic resistance genes to bacterial pathogens.

Water Res 2021 Jul 20;202:117447. Epub 2021 Jul 20.

Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.

Human activities can accelerate the antibiotic resistome prevalence and pose threats to ecological safety and public health globally. However, antibiotic resistance gene (ARG) mobility and dissemination into bacterial pathogens under anthropogenic disturbances are still poorly understood. Here, we used a metagenomic approach to profile the biogeography of ARGs and pathogenic antibiotic resistant bacteria (PARB) under anthropogenic disturbances along the Yarlung Tsangpo River. Results showed the ARGs was dominated by bacA gene along the Yarlung Tsangpo River on the Tibetan Plateau. The ARG composition was differently impacted by rapid urbanization and dam construction, which urbanization could promote ARGs resistant to sulfonamide and tetracycline, whereas dam construction could elevate the resistance to chloramphenicol and aminoglycoside. Land use pattern was identified as a critical factor influencing ARG composition under anthropogenic disturbances, as it could directly reflect the land degradation level and indicate the inputs of ARG-selective chemicals of different human activities. Moreover, despite of the lack of variation in ARG relative abundance, PARB were highly promoted by anthropogenic activities, indicating increasing ARG dissemination to pathogen. We found that human-impacted environments harbored high proportion of mobile genetic elements (MGEs), and the MGE carrying ARGs also increased under anthropogenic disturbances in the pathogenic hosts, which confirmed that anthropogenic activities could promote ARG horizontal gene transfer. Furthermore, anthropogenic activities could influence PARB assembly processes. Basically, stochastic processes dominated PARB assembly along the river, and with increasing level of anthropogenic activities, these processes shifted from undominated stochastic processes to dispersal limitation. In summary, this study provides useful strategies in watershed resistome management and reduction of ARG dissemination to pathogens, which should consider the mode and intensity of human activity and its potential influence on horizontal gene transfer and assembly processes.
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http://dx.doi.org/10.1016/j.watres.2021.117447DOI Listing
July 2021

Removal of low concentrations of nickel ions in electroplating wastewater using capacitive deionization technology.

Chemosphere 2021 Jun 29;284:131341. Epub 2021 Jun 29.

State Key Joint Laboratory of Environment Simulation and Pollution Control (SKLESPC), Beijing Key Laboratory for Emerging Organic Contaminants Control, School of Environment, Tsinghua University, Beijing, 100084, China. Electronic address:

The capacitive deionization (CDI) technology was adopted to reduce the low concentrations of nickel in electroplating wastewater to meet the discharge standard. The composite anode and the composite cathode (Resin-CGA) were prepared by incorporating anion-exchange resin (AR-CGA) and cation exchange resin (CR-CGA) into the titanium mesh by the conductive graphite adhesive, respectively. The electrolytic performances of the Resin-CGA electrodes at different cell voltages, initial electrolyte pH and initial nickel concentrations were investigated. The adsorbed amount of nickel on the CR-CGA electrodes and the removal percentage of nickel were 0.095 mg g and 95%, respectively. The Ni concentrations were reduced to 0.005 mg L and the electricity consumption was 1.6 kWh per ton of the electroplating wastewater at the initial Ni concentrations of 1.0 mg L under the optimal conditions, exhibiting better electrolytic performance than the cation-exchange resin and the electrodes prepared by the conductivity graphite adhesive (CGA). In addition, the spent electrodes were electrochemically regenerated and the electrolytic performance of the Resin-CGA electrodes kept stable during the cycles. This study provided a promising method to reduce the low concentrations of Ni to less than 0.1 mg L in the treatment of electroplating wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131341DOI Listing
June 2021

Genetic vulnerabilities upon inhibition of DNA damage response.

Nucleic Acids Res 2021 Jul 28. Epub 2021 Jul 28.

Departments of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Because of essential roles of DNA damage response (DDR) in the maintenance of genomic integrity, cellular homeostasis, and tumor suppression, targeting DDR has become a promising therapeutic strategy for cancer treatment. However, the benefits of cancer therapy targeting DDR are limited mainly due to the lack of predictive biomarkers. To address this challenge, we performed CRISPR screens to search for genetic vulnerabilities that affect cells' response to DDR inhibition. By undertaking CRISPR screens with inhibitors targeting key DDR mediators, i.e. ATR, ATM, DNAPK and CHK1, we obtained a global and unbiased view of genetic interactions with DDR inhibition. Specifically, we identified YWHAE loss as a key determinant of sensitivity to CHK1 inhibition. We showed that KLHL15 loss protects cells from DNA damage induced by ATM inhibition. Moreover, we validated that APEX1 loss sensitizes cells to DNAPK inhibition. Additionally, we compared the synergistic effects of combining different DDR inhibitors and found that an ATM inhibitor plus a PARP inhibitor induced dramatic levels of cell death, probably through promoting apoptosis. Our results enhance the understanding of DDR pathways and will facilitate the use of DDR-targeting agents in cancer therapy.
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http://dx.doi.org/10.1093/nar/gkab643DOI Listing
July 2021

Suppression of LjBAK1-mediated immunity by SymRK promotes rhizobial infection in Lotus japonicus.

Mol Plant 2021 Jul 24. Epub 2021 Jul 24.

State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address:

An important question in biology is how organisms can associate with different microbes that pose no threat (commensals), pose a severe threat (pathogens) and those that are beneficial (symbionts). The root nodule symbiosis serves as important model system to address such questions in the context of plant-microbe interactions. It is now generally accepted that rhizobia have the abilities to actively suppress host immune responses during the infection process, analogous to the way in which plant pathogens can evade immune recognition. However, much remains to be elucidated with regard to the mechanisms by which the host recognizes the rhizobia as pathogens and how, subsequently, these pathways are suppressed to allow establishment of the nitrogen fixing symbiosis. In this study, we found that SymRK (Symbiosis Receptor-like Kinase) is required for rhizobial suppression of plant innate immunity in Lotus japonicus. SymRK associates with LjBAK1 (BRASSINOSTEROID INSENSITIVE 1-Associated receptor Kinase 1), a well characterized, positive regulator of plant innate immunity, and directly inhibits LjBAK1 kinase activity. Rhizobial inoculation enhances the association between SymRK and LjBAK1 in planta. LjBAK1 is required to regulate plant innate immunity and plays a negative role in mediating rhizobial infection in L. japonicus. The data indicate that the protein complex of SymRK-LjBAK1 serves as an intersection point between rhizobial symbiotic signaling pathways and innate immunity pathways, which provides an evidence that rhizobia might actively suppress the host's ability to mount a defense response in the legume-rhizobium symbiosis.
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http://dx.doi.org/10.1016/j.molp.2021.07.016DOI Listing
July 2021

Type V Collagen Regulates the Structure and Biomechanics of TMJ Condylar Cartilage: A Fibrous-Hyaline Hybrid.

Matrix Biol 2021 Jul 24. Epub 2021 Jul 24.

School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States. Electronic address:

This study queried the role of type V collagen in the post-natal growth of temporomandibular joint (TMJ) condylar cartilage, a hybrid tissue with a fibrocartilage layer covering a secondary hyaline cartilage layer. Integrating outcomes from histology, immunofluorescence imaging, electron microscopy and atomic force microscopy-based nanomechanical tests, we elucidated the impact of type V collagen reduction on TMJ condylar cartilage growth in the type V collagen haploinsufficiency and inducible knockout mice. Reduction of type V collagen led to significantly thickened collagen fibrils, decreased tissue modulus, reduced cell density and aberrant cell clustering in both the fibrous and hyaline layers. Post-natal growth of condylar cartilage involves the chondrogenesis of progenitor cells residing in the fibrous layer, which gives rise to the secondary hyaline layer. Loss of type V collagen resulted in reduced proliferation of these cells, suggesting a possible role of type V collagen in mediating the progenitor cell niche. When the knockout of type V collagen was induced in post-weaning mice after the start of physiologic TMJ loading, the hyaline layer exhibited pronounced thinning, supporting an interplay between type V collagen and occlusal loading in condylar cartilage growth. The phenotype in hyaline layer can thus be attributed to the impact of type V collagen on the mechanically regulated progenitor cell activities. In contrast, knee cartilage does not contain the progenitor cell population at post-natal stages, and develops normal structure and biomechanical properties with the loss of type V collagen. Therefore, in the TMJ, in addition to its established role in regulating the assembly of collagen I fibrils, type V collagen also impacts the mechanoregulation of progenitor cell activities in the fibrous layer. We expect such knowledge to establish a foundation for understanding condylar cartilage matrix development and regeneration, and to yield new insights into the TMJ symptoms in patients with classic Ehlers-Danlos syndrome, a genetic disease due to autosomal mutation of type V collagen.
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http://dx.doi.org/10.1016/j.matbio.2021.07.002DOI Listing
July 2021

Effects of transforming forest land into terraced land on the characteristics of soil carbon, nitrogen, phosphorus and their stoichiometry in North Guangdong, China.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2440-2448

College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642, China.

To examine the effects of land use change on soil stoichiometry, we selected four kinds of land use soils in northern Guangdong: forest land (FL), sloping orchard (SO), dry land terraces (DLT) and paddy terraces (PT) to explore the changes of the contents, stocks and stoichiometry of organic carbon, nitrogen and phosphorus in the 20 a process of transforming from forest land into terraced land. Results showed that land use significantly changed the contents and stoichiometric characteristics of soil carbon, nitrogen and phosphorus. With the increase of soil depth, organic carbon (OC) and total nitrogen (TN) contents of DLT and PT decreased significantly, while FL and SO showed a "V"-shaped change trend. There was no difference in total phosphorus (TP) content among the four land use types. The OC content of PT was the highest, with an average value of 12.36 g·kg, followed by FL (10.32 g·kg) and DLT (8.80 g·kg), while SO was the lowest (5.96 g·kg). TN content was decreased in order of PT (1.01 g·kg)>DLT (0.78 g·kg)>FL (0.66 g·kg)>SO (0.33 g·kg). TP content of DLT (0.71 g·kg) was the highest, and SO (0.22 g·kg) was the lowest. C:N was between 8.87 and 22.94, and SO was the highest. C:P was between 8.73 and 81.74, N:P was between 0.77 and 5.13, with both of which being the highest in FL. Land use, soil depth and their interaction significantly affected the contents, stocks, and stoichiometric ratio of soil carbon, nitrogen and phosphorus, with soil bulk density, pH, and clay content as important influencing factors. The research results could provide a scientific basis for land use of subtropical low mountain forest land and rational fertilization of terraced ecosystems.
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http://dx.doi.org/10.13287/j.1001-9332.202107.024DOI Listing
July 2021

Sustainable production of benzylamines from lignin.

Angew Chem Int Ed Engl 2021 Jul 23. Epub 2021 Jul 23.

Dalian Institute of Chemical Physics, CAS Key Laboratory of Science and Technology on Applied Catalysis, CHINA.

Catalytic conversion of lignin into heteroatom functionalized chemicals is of great importance to bring the biorefinery concept into reality. Herein, a new strategy was designed for direct transformation of lignin β-O-4 model compounds into benzylamines and phenols in moderate to excellent yields in the presence of organic amines. The transformation involves dehydrogenation of C α -OH, hydrogenolysis of the C β -O bond and reductive amination in the presence of Pd/C catalyst. Experimental data suggest that the dehydrogenation reaction proceeds over the other two reactions and that secondary amines serve as both reducing agents and amine sources in the transformation. Moreover, the concept of "lignin to benzylamines" was demonstrated by a two-step process. This work represents a first example of synthesis of benzylamines from lignin, thus providing a new opportunity for the sustainable synthesis of benzylamines from renewable biomass, and expanding the products pool of biomass conversion to meet future biorefinery demands.
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http://dx.doi.org/10.1002/anie.202105973DOI Listing
July 2021

Multifunctional starch-based material for contaminated emulsions separation and purification.

Carbohydr Polym 2021 Oct 18;269:118354. Epub 2021 Jun 18.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.

Stable water-in-oil (W/O) emulsions can produce at many industrial production occasions. However, most materials for its separation have serious fouling problems. To overcome this shortcoming, we fabricated an easy cleaning multifunctional starch-based material with unique wetting behavior which could realize efficient separation and purification of W/O emulsions. This material has a hierarchical structure and superoleophilic and under oil superhydrophobic surfaces which could separate various W/O emulsions in a high separation efficiency and flux without external pressure. In addition, the decrease of separation flux was not observed for this material, which can be reused more than 10 times after washing with ethanol and drying after each separation cycle. Furthermore, this material also could realize efficient removal of dyes and heavy-metal and rare-earth ions simultaneously during a separation process. The material shows great potential for separating and purifying stable W/O emulsions produced during the industrial production.
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http://dx.doi.org/10.1016/j.carbpol.2021.118354DOI Listing
October 2021

Ultralow Resistance Two-Stage Electrostatically Assisted Air Filtration by Polydopamine Coated PET Coarse Filter.

Small 2021 Jul 26:e2102051. Epub 2021 Jul 26.

Department of Nuclear Science and Engineering and Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Airborne particulate matters (PM) pose serious health threats to the population, and efficient filtration is needed for indoor and vehicular environments. However, there is an intrinsic conflict between filtration efficiency, air resistance, and service life. In this study, a two-stage electrostatically assisted air (EAA) filtration device is designed and the efficiency-air resistance-filter life envelope is significantly improved by a thin coating of polydopamine (PDA) on the polyethylene terephthalate (PET) coarse filter by in situ dopamine polymerization. The 8 mm thick EAA [email protected] filter has a high filtration efficiency of 99.48% for 0.3 µm particles, low air resistance of 9.5 Pa at a filtration velocity of 0.4 m s , and steady performance up to 30 d. Compared with the bare PET filter, the penetration rate for 0.3 µm particles is lowered by 20×. The coated PDA is of submicron thickness, 10  × the gap distance between filter fibers, so low air resistance could be maintained. The filter shows steadily high filtration efficiency and an acceptable increase of air resistance and holds nearly as many particles as its own weight in a 30 day long-term test. The working mechanism of the EAA coarse filter is investigated, and the materials design criteria are proposed.
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http://dx.doi.org/10.1002/smll.202102051DOI Listing
July 2021

Radiological and Clinical Findings of Multiple Cerebellar Liponeurocytoma: A Case Report.

Front Surg 2021 7;8:686892. Epub 2021 Jul 7.

Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Cerebellar liponeurocytoma is an extremely rare benign tumor which generally occurs in cerebellum and is almost always solitary. Multifocal cerebellar liponeurocytoma is exceedingly rare, only 8 cases has been reported so far. Herein we present the 9th case of multifocal cerebellar liponeurocytoma in a 70-year-old woman with the complete clinical course and comprehensive imaging findings. A 70-year-old woman presented with a history of intermittent headache for 5 years. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain have been performed and suggested a diagnosis of teratoma based on the imaging findings. After the surgical resection of the lesion, histopathological and immunohistochemical analyses revealed neuronal, glial, and lipomatous components and confirmed the diagnosis of multifocal cerebellar liponeurocytoma after surgical resection. During the 2-year follow-up period, the patient showed no signs of recurrence or metastasis. We described the radiological characteristics and clinical course of an exceedingly rare case of multifocal cerebellar liponeurocytoma in the cerebellar vermis and temporal lobe. The clear multifocality makes this case unusual.
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http://dx.doi.org/10.3389/fsurg.2021.686892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293275PMC
July 2021

Investigation of Charge Performance in Anatase TiO Powder for Methane Conversion by Vis-NIR Spectroscopy.

ACS Catal 2021 Jul 20;11(13):8226-8238. Epub 2021 Jun 20.

Department of Chemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.

The intrinsic behavior of photogenerated charges and reactions with chemicals are key for a photocatalytic process. To observe these basic steps is of great importance. Here we present a reliable and robust system to monitor these basic steps in powder photocatalysts, and more importantly to elucidate the key issue in photocatalytic methane conversion over the benchmark catalyst TiO. Under constant excitation, the absorption signal across the NIR region was demonstrated to be dominated by photoexcited electrons, the absorption of photoexcited holes increases toward shorter wavelengths in the visible region, and the overall shapes of the photoinduced absorption spectra obtained using the system demonstrated in the present work are consistent with widely accepted transient absorption results. Next, measurements provide direct experimental evidence that the initial step of methane activation over TiO involves oxidation by photoexcited holes. It is calculated that 90 ± 6% of photoexcited electrons are scavenged by O (in dry air), 61 ± 9% of photoexcited holes are scavenged by methane (10% in argon), and a similar amount of photoexcited electrons can be scavenged by O even when the O concentration is reduced by a factor of 10. The present results suggest that O is much more easily activated in comparison to methane over anatase TiO, which rationalizes the much higher methane/O ratio frequently used in practice in comparison to that required stoichiometrically for photocatalytic production of value-added chemicals via methane oxidation with oxygen. In addition, methanol (a preferable product of methane oxidation) is much more readily oxidized than methane over anatase TiO.
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http://dx.doi.org/10.1021/acscatal.1c01998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291573PMC
July 2021

Blood Genomics Identifies Three Subtypes of Systemic Lupus Erythematosus: "IFN-High," "NE-High," and "Mixed".

Mediators Inflamm 2021 1;2021:6660164. Epub 2021 Jul 1.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.

Purpose: Systemic lupus erythematosus (SLE) is a systemic and multifactorial autoimmune disease, and its diverse clinical manifestations affect molecular diagnosis and drug benefits. Our study was aimed at defining the SLE subtypes based on blood transcriptome data, analyzing functional patterns, and elucidating drug benefits.

Methods: Three data sets were used in this paper that were collected from the Gene Expression Omnibus (GEO) database, which contained two published data sets of pediatric and adult SLE patients (GSE65391, GSE49454) and public longitudinal data (GSE72754) from a cohort of SLE patients treated with IFN- Kinoid (IFN-K). Based on disease activity scores and gene expression data, we defined a global SLE signature and merged three clustering algorithms to develop a single-sample subtype classifier (SSC). Systematic analysis of coexpression networks based on modules revealed the molecular mechanism for each subtype.

Results: We identified 92 genes as a signature of the SLE subtypes and three intrinsic subsets ("IFN-high," "NE-high," and "mixed"), which varied in disease severity. We speculated that IFN-high might be due to the overproduction of interferons (IFNs) caused by viral infection, leading to the formation of autoantibodies. NE-high might primarily result from bacterial and fungal infections that stimulated neutrophils (NE) to produce neutrophil extracellular traps (NETs) and induced individual autoimmune responses. The mixed type contained both of these molecular mechanisms and showed an intrinsic connection.

Conclusions: Our research results indicated that identifying the molecular mechanism associated with different SLE subtypes would benefit the molecular diagnosis and stratified therapy. Moreover, repositioning of IFN-K based on subtypes also revealed an improved therapeutic effect, providing a new direction for disease treatment and drug development.
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http://dx.doi.org/10.1155/2021/6660164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270691PMC
July 2021

Individuals with and without military-related PTSD differ in subjective sleepiness and alertness but not objective sleepiness.

J Psychiatr Res 2021 Jul 14;141:301-308. Epub 2021 Jul 14.

University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Posttraumatic stress disorder-related sleep disturbances may increase daytime sleepiness and compromise performance in individuals with posttraumatic stress disorder. We investigated nighttime sleep predictors of sleepiness in Veterans with and without posttraumatic stress disorder. Thirty-seven post-9/11 Veterans with posttraumatic stress disorder and 47 without posttraumatic stress disorder (Control) completed a 48-h lab stay. Nighttime quantitative EEG and sleep architecture parameters were collected with polysomnography. Data from daytime sleepiness batteries assessing subjective sleepiness (global vigor questionnaire), objective sleepiness (Multiple Sleep Latency Tests) and alertness (psychomotor vigilance task) were included in analyses. Independent samples t-tests and linear regressions were performed to identify group differences in sleepiness and nighttime sleep predictors of sleepiness in the overall sample and within each group. Participants with posttraumatic stress disorder had higher subjective sleepiness (t = 4.20; p < .001) and lower alertness (psychomotor vigilance task reaction time (t = -3.70; p < .001) and lapses: t = -2.13; p = .04) than the control group. Objective daytime sleepiness did not differ between groups (t = -0.79, p = .43). In the whole sample, higher rapid eye movement delta power predicted lower alertness quantified by psychomotor vigilance task reaction time (β = 0.372, p = .013) and lapses (β = 0.388, p = .013). More fragmented sleep predicted higher objective sleepiness in the posttraumatic stress disorder group (β = -.467, p = .005) but no other nighttime sleep measures influenced the relationship between group and sleepiness. Objective measures of sleep and sleepiness were not associated with the increased subjective sleepiness and reduced alertness of the posttraumatic stress disorder group.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.017DOI Listing
July 2021

Effects of chlorine disinfectants on the microbial community structure and the performance of anaerobic digestion of swine manure.

Bioresour Technol 2021 Jul 17;339:125576. Epub 2021 Jul 17.

Northwest A&F University, College of Mechanical and Electronic Engineering, Yangling, Shaanxi 712100, China; Northwest Research Center of Rural Renewable Energy Exploitation and Utilization of M.O.A, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

The residual chlorine disinfectants (CDs) in swine slurry could negatively impact the anaerobic digestion (AD). The objective of this study was to investigate the effects of CDs on mesophilic and thermophilic AD. The results indicated that CDs exerted inhibition effects on methanogenesis at the initial stage of mesophilic AD, leading to the extension of lag time from 0.62 days for control to 0.85, 1.9, 3.8, and 5.5 days with the increasing CDs concentrations of 50, 100, 200, and 400 mg/L, respectively. Under thermophilic condition, the inhibition effects reduced significantly at the initial stage but a decrease of CMP at later stage was observed. The microbial analysis revealed that CDs resulted in the enrichment of chlorine-resistant bacteria (Clostridum_sensu_stricto_1) and archaea (Methanosarcina). Addition of activated carbon (AC), zero-valent iron (ZVI) and biochar (BC) was evaluated for alleviating the inhibitions of CDs and proved to be feasible strategies to alleviate the inhibited AD.
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http://dx.doi.org/10.1016/j.biortech.2021.125576DOI Listing
July 2021

Big Data Technology Applications and the Right to Health in China during the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 07 8;18(14). Epub 2021 Jul 8.

Faculty of Law, University of Macau, Taipa, Macao 999078, China.

Individuals have the right to health according to the Constitution and other laws in China. Significant barriers have prevented the full realisation of the right to health in the COVID-19 era. Big data technology, which is a vital tool for COVID-19 containment, has been a central topic of discussion, as it has been used to protect the right to health through public health surveillance, contact tracing, real-time epidemic outbreak monitoring, trend forecasting, online consultations, and the allocation of medical and health resources in China. Big data technology has enabled precise and efficient epidemic prevention and control and has improved the efficiency and accuracy of the diagnosis and treatment of this new form of coronavirus pneumonia due to Chinese institutional factors. Although big data technology has successfully supported the containment of the virus and protected the right to health in the COVID-19 era, it also risks infringing on individual privacy rights. Chinese policymakers should understand the positive and negative impacts of big data technology and should prioritise the Personal Information Protection Law and other laws that are meant to protect and strengthen the right to privacy.
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http://dx.doi.org/10.3390/ijerph18147325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307229PMC
July 2021

Excessive nitrogen application under moderate soil water deficit decreases photosynthesis, respiration, carbon gain and water use efficiency of maize.

Plant Physiol Biochem 2021 Jul 15;166:1065-1075. Epub 2021 Jul 15.

State Engineering Laboratory of Efficient Water Use of Crops and Disaster Loss Mitigation, Key Laboratory of Dryland Agriculture, Ministry of Agriculture and Rural Affairs of China, Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing, China. Electronic address:

The impact of water stress and nitrogen (N) nutrition on leaf respiration (R), carbon balance and water use efficiency (WUE) remains largely elusive. Therefore, the objective of the present study was to investigate the effect of soil water and N stresses on growth, physiological responses, leaf structure, carbon gain and WUE of maize. The plants were subjected to different soil water and N regimes to maturity. The results showed that the photosynthesis (A) and stomatal conductance (G) decreased significantly under the water stressed treatments across the N treatments mainly ascribed to the decreased plant water status. The moderate water stress reduced the photosynthetic capacity and activity and also caused damage to the structure of leaves, resulting in the significant reduction of A, and thus decreased WUE. The dark respiration (R) was significantly decreased due to the damage of mitochondria, however, the R/A increased significantly and the carbon gain was seriously compromised, eventually inhibiting biomass growth under the moderately water stressed treatment. Increasing N dose further aggravated the severity of water deficit, decreased A, G and WUE, damaged the structure and reduced the number of mitochondria of leaves, while increased R/A considerably under moderate water stress. Consequently, the biomass accumulation, carbon gain and plant level WUE in the moderately water stressed treatment decreased markedly under the high N supply. Therefore, excessive N application should be avoided when plants suffer soil water stress in maize production.
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http://dx.doi.org/10.1016/j.plaphy.2021.07.014DOI Listing
July 2021

A Sensitive and Reliable Organic Fluorescent Nanothermometer for Noninvasive Temperature Sensing.

J Am Chem Soc 2021 Jul 21. Epub 2021 Jul 21.

Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.

Sensing temperature at the subcellular level is of great importance for the understanding of miscellaneous biological processes. However, the development of sensitive and reliable organic fluorescent nanothermometers remains challenging. In this study, we report the fabrication of a novel organic fluorescent nanothermometer and study its application in temperature sensing. First of all, we synthesize a dual-responsive organic luminogen that can respond to the molecular state of aggregation and environmental polarity. Next, natural saturated fatty acids with sharp melting points as well as reversible and rapid phase transition are employed as the encapsulation matrix to correlate external heat information with the fluorescence properties of the luminogen. To apply the composite materials for biological application, we formulate them into colloidally dispersed nanoparticles by a technique that combines surface polymerization and nanoprecipitation. As anticipated, the resultant zwitterionic nanothermometer exhibits sensitive, reversible, reliable, and multiparametric responses to temperature variation within a narrow range around the physiological temperature (i.e., 37 °C). Taking spectral position, fluorescence intensity, and fluorescence lifetime as the correlation parameters, the maximum relative thermal sensitivities are determined to be 2.15% °C, 17.06% °C, and 17.72% °C, respectively, which are much higher than most fluorescent nanothermometers. Furthermore, we achieve the multimodal temperature sensing of bacterial biofilms using these three complementary fluorescence parameters. Besides, we also fabricate a cationic form of the nanothermometer to facilitate efficient cellular uptake, holding great promise for studying thermal behaviors in biological systems.
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http://dx.doi.org/10.1021/jacs.1c04597DOI Listing
July 2021

The incidence of sympathetic ophthalmia after trauma: A meta-analysis.

Am J Ophthalmol 2021 Jul 17. Epub 2021 Jul 17.

Department of Ophthalmology and Visual Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making.

Design: Systematic review and meta-analysis.

Methods: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920.

Results: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I of 13% and 72%, respectively.

Conclusions: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.
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http://dx.doi.org/10.1016/j.ajo.2021.06.036DOI Listing
July 2021

Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study.

Gynecol Endocrinol 2021 Jul 20:1-7. Epub 2021 Jul 20.

Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Objective: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model.

Methods: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment.

Results: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group.

Conclusions: TSP-1 delivery system might be an alternative therapy for PCOS treatment.
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http://dx.doi.org/10.1080/09513590.2021.1950682DOI Listing
July 2021

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

Mikrochim Acta 2021 07 20;188(8):262. Epub 2021 Jul 20.

Institute of Marine Science and Technology, Shandong University, Qingdao, 266000, China.

COVID-19 is now a severe threat to global health. Facing this pandemic, we developed a space-encoding microfluidic biochip for high-throughput, rapid, sensitive, simultaneous quantitative detection of SARS-CoV-2 antigen proteins and IgG/IgM antibodies in serum. The proposed immunoassay biochip integrates the advantages of graphene oxide quantum dots (GOQDs) and microfluidic chip and is capable of conducting multiple SARS-CoV-2 antigens or IgG/IgM antibodies of 60 serum samples simultaneously with only 2 μL sample volume of each patient. Fluorescence intensity of antigens and IgG antibody detection at emission wavelength of ~680 nm was used to quantify the target concentration at excitation wavelength of 632 nm, and emission wavelength of ~519 nm was used during the detection of IgM antibodies at excitation wavelength of 488 nm. The method developed has a large linear quantification detection regime of 5 orders of magnitude, an ultralow detection limit of ~0.3 pg/mL under optimized conditions, and less than 10-min qualitative detection time. The proposed biosensing platform will not only greatly facilitate the rapid diagnosis of COVID-19 patients, but also provide a valuable screening approach for infected patients, medical therapy, and vaccine recipients.
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http://dx.doi.org/10.1007/s00604-021-04896-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289455PMC
July 2021

Combining high resolution mass spectrometry with a halogen extraction code to characterize and identify brominated disinfection byproducts formed during ozonation.

Sci Total Environ 2021 Jul 13;796:149016. Epub 2021 Jul 13.

Environmental Simulation and Pollution Control State Key Joint Laboratory, State Environmental Protection Key Laboratory of Microorganism Application and Risk Control (SMARC), Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental Safety, Institute of Environment and Ecology, Tsinghua-Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, PR China. Electronic address:

Ozonation is widely used during water treatment but can generate a variety of toxic disinfection byproducts, especially in the presence of bromide. In the present study, our halogen extraction code was extended and modified to identify bromine isotopic patterns and combined with the R package MFAssignR in selectively identifying brominated disinfection byproducts (Br-DBPs) from high resolution mass spectra. In total, 127 Br-DBPs formed from a Suwannee River natural organic matter (SRNOM) solution were successfully detected from tens of thousands of mass spectrometry peaks. Kendrick mass defect analysis and structural characterization identified 17 structures, 15 of which were identified as brominated carboxylic acids and firstly reported here. Computational model predictions indicated that these brominated carboxylic acids may possess high toxic potencies and raise valid concerns. The adapted halogen extraction code described in this study is a powerful tool for a wider application of analyzing Br-DBPs in complex water matrices and provides an effective technique to characterize and identify these compounds in future studies.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149016DOI Listing
July 2021

Unnecessity of Routine Dissection of Right Central Lymph Nodes in cN0 Papillary Thyroid Carcinoma Located at the Left Thyroid Lobe.

Front Oncol 2021 1;11:685708. Epub 2021 Jul 1.

Department of Thyroid and Head Neck, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Objective: The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is an important part of the central lymph nodes (LNs). We aimed to explore the rate and predictors of LN-prRLN metastasis in cN0 papillary thyroid carcinoma (PTC) located at the left thyroid lobe.

Methods: Patients with surgically treated primary left lobe PTC were retrospectively enrolled. The metastatic distribution of LN-prRLN and postoperative complications were assessed. The association between LN-prRLN metastasis and clinicopathological variables was evaluated by univariate and multivariate analyses.

Results: A total of 857 patients were included for the analysis. Central LN metastasis was noted in 310 (35.3%) cases. The most (27.6%) and least (1.7%) commonly involved LNs were the left paratracheal LN and the LN-prRLN. In the univariate analysis, the tumor size, multifocality, the extent of extrathyroidal extension (none macroscopic macroscopic maximal), and perineural invasion were associated with positive LN-prRLN. In the multivariate analysis, tumor size of >40.0 mm and macroscopic maximal invasion were found as the only two independent predictors. Transient and permanent hypoparathyroidism were noted in 90 (10.2%) and 13 (1.5%) patients, respectively. Voice change was noted in 40 (4.6%) patients, and 20 patients recovered.

Conclusions: In cN0 PTC located at the left lobe, LN-prRLN metastasis was very uncommon. We found that LN-prRLN dissection is not required routinely, but should be performed if the tumor size is >40.0 mm and macroscopic maximal extrathyroidal extension is present.
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http://dx.doi.org/10.3389/fonc.2021.685708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281883PMC
July 2021

Ecological insights into the disturbances in bacterioplankton communities due to emerging organic pollutants from different anthropogenic activities along an urban river.

Sci Total Environ 2021 Jul 10;796:148973. Epub 2021 Jul 10.

Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.

Emerging organic pollutants (EOPs) in urban rivers have raised concerns regarding their eco-toxicological effects. However, the bacterioplankton community disturbances caused by EOPs in urban rivers and the associated ecological mechanisms remain unclear. This study provided profiles of the spatial distribution of a bacterioplankton community disturbed by human activity along an urban river. The results showed that EOP concentration and composition were differently distributed in residential and industrial areas, which significantly influenced bacterioplankton community structure. Based on redundancy analysis, parabens (methylparaben and propylparaben) were the major factors driving bacterioplankton community changes. Parabens inhibited gram-positive bacteria and promoted oxidative stress-tolerant bacteria in the river ecosystem. Parabens also disturbed ecological processes of bacterioplankton community assembly, shifting from a homogeneous selection (consistent selection pressure under similar environmental condition) to stochastic processes (random changes due to birth, death, immigration, and emigration) with changing in paraben concentrations. Heterogeneous selection was predicted to dominate microbial community assembly with paraben concentration changes exceeding 61.6 ng/L, which could deteriorate the river ecosystem. Furthermore, specific bacterial genera were identified as potential bioindicators to assess the condition of EOP contaminants in the river. Overall, this study highlights significant disturbances in bacterioplankton communities by EOPs at environmental concentrations, and our results could facilitate generation of appropriate management strategies aimed at EOPs in urban rivers.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148973DOI Listing
July 2021

Effect of long working hours and insomnia on depressive symptoms among employees of Chinese internet companies.

BMC Public Health 2021 Jul 16;21(1):1408. Epub 2021 Jul 16.

National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Xicheng District, Beijing, P.R. China, 100050.

Background: In China, long working hours and insomnia are relatively common among internet company employees. Considering that both can affect mental health, we examined their independent and interaction effects on these employees' depressive symptoms (DS).

Methods: We analyzed data from the 2016 occupational health questionnaire survey conducted in 35 large-, medium-, and small-scale internet companies. Overall, 3589 full-time employees were recruited to evaluate the association among working hours, insomnia, and DS. The Patient Health Questionnaire (PHQ-9) was used to assess DS. The association of DS (PHQ-9 ≥ 10) with working hours (≤40, 41-50, 51-60, and > 60 h/week), insomnia (with or without), and interaction of both was estimated using multivariable logistic regression analysis.

Results: Compared with the group working for ≤40 h/week, the adjusted odds ratios (ORs) for DS among participants who worked for 41-50 h/week, 51-60 h/week, and > 60 h/week were 1.32 (1.11-1.56), 1.74 (1.35-2.24), and 2.54 (1.90-3.39), respectively. The ORs for DS among those with insomnia were 2.36 (2.04-2.74) after adjusting for general characteristics. The ORs for DS related to insomnia were similar [1.91 (1.46-2.50), 2.00 (1.61-2.50), respectively] in the participants who worked for < 50 h/week. However, among participants working for 51-60 h or > 60 h/week, the adjusted ORs for DS substantially increased to 4.62 (2.90-7.37) and 5.60 (3.36-9.33), respectively. Moreover, among the participants with insomnia, working overtime showed a greater association with DS.

Conclusions: We showed that long working hours and insomnia are independent factors associated with the prevalence of DS; furthermore, an interaction effect of long working hours and insomnia on DS was observed. For relieving DS in internet company employees, it is important to reduce insomnia.
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http://dx.doi.org/10.1186/s12889-021-11454-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283851PMC
July 2021

Continuous photocatalysis via photo-charging and dark-discharging for sustainable environmental remediation: Performance, mechanism, and influencing factors.

J Hazard Mater 2021 Jul 8;420:126607. Epub 2021 Jul 8.

School of Environmental Science and Engineering, Southern University of Science and Technology, Xueyuan Road #1088, Shenzhen 518055, PR China.

Continuous photocatalysis via photo-charging and dark-discharging presents a paradigm shift in conventional photocatalysis with the requirement of continuous illumination to maintain the catalytic activity. This is expected to meet the ever-increasing demand for sustainable development of energy and environment driven by natural day-night cycles. Substantial advances in continuous photocatalysis for various environmental applications under light-dark cycles have been witnessed during the last decade. However, there lacks a systematic and critical review on basic but important information of continuous photocatalysis for environmental remediation, challenging robust scientific progress of this technology towards potential practical use. Here, the general description of continuous photocatalysis involving energy storage mechanisms (hole and electron storage) and characterizations (electron storage behaviors, release behaviors and storage capacity) has been first introduced. Importantly, the remediation performance and mechanism of continuous photocatalysis for environmental applications are qualitatively and quantitatively demonstrated, including chemical pollutant oxidation and reduction, microbial pathogen inactivation, and multifunctional treatment. In addition, key factors influencing its remediation performance are analyzed, for the first time, from both operational and environmental views. The ample opportunities in the field of continuous photocatalysis for sustainable environmental remediation are also pointed out, calling for more efforts to fill current knowledge gaps in the future.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126607DOI Listing
July 2021

Mechanisms for the dissolved biochar promoted iron dissolution and consequential chromium release.

Sci Total Environ 2021 Jul 9;796:148923. Epub 2021 Jul 9.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China. Electronic address:

Biochar is widely applied in soil for agricultural and environmental purposes. Soluble fraction of biochar may be released from bulk biochar as dissolved biochar (DBC) after irrigation or rainfall. DBC had been reported to possess high chemical activity in aqueous system, while less attention was paid to the impact of DBC on the soil environmental processes. In this work, the impact of DBC on ferric (hydro) oxides was systematically examined. Our study showed that DBC prepared from rice straw could significantly promote the dissolution of ferric oxides with unstable and metastable crystalline structures, e.g., ferrihydrite under relatively acidic condition. Organic ligand-promoted dissolution was the main mechanism for iron release from ferrihydrite, and the low-molecular-weight DBC component (less than 1000 Da) was the major contributor for this process. Furthermore, the organic carbon content normalized ligand-promoted dissolution capacity for DBC was much higher than common dissolved organic matters. More importantly, DBC could promote the release of Cr from dichromate-adsorbed ferric mineral. Our results suggest that in soils with relatively low pH and high contents of ferric hydroxides, e.g., red soil in southern China, DBC derived from applied biochar could enhance the mobility and bioavailability of iron and other heavy metals. The dissolved metals would play active roles in soil redox cycle and biotic processes. Therefore, it's necessary to evaluate the long-term impact of biochar application on acidic field soils with high iron content.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148923DOI Listing
July 2021

Evolutionary Multitasking Multilayer Network Reconstruction.

IEEE Trans Cybern 2021 Jul 16;PP. Epub 2021 Jul 16.

Due to the multilayer nature of real-world systems, the problem of inferring multilayer network structures from nonlinear and complex dynamical systems is prominent in many fields, including engineering, biological, physical, and computer sciences. Many network reconstruction methods have been proposed to address this problem, but none of them consider the similarities among network reconstruction tasks at different component layers, which are inspired by topology correlations and dynamic couplings among different component layers. This article develops an evolutionary multitasking multilayer network reconstruction framework to make use of the correlations among different component layers to improve the reconstruction performance; we refer to this framework as EM2MNR. In EM2MNR, the multilayer network reconstruction problem is first established as a multitasking multilayer network reconstruction problem, where the goal of each task is to reconstruct the network structure of a component layer. In addition, multitasking multilayer network reconstruction problems are high dimensional, but existing evolutionary multitasking algorithms may have poor performance when dealing with optimization problems with a high-dimensional search space. Inspired by the sparsity of multilayer networks, EM2MNR employs the restricted Boltzmann machine to extract low effective features from the original decision space and then decides whether to conduct knowledge transfer on these features. To verify the performance of EM2MNR, this article also designs a test suite for multilayer network reconstruction problems. The experimental results demonstrate the significant improvement obtained by the proposed EM2MNR framework on 96 multilayer network reconstruction problems.
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http://dx.doi.org/10.1109/TCYB.2021.3090769DOI Listing
July 2021

1 kHz, 430 mJ, sub-nanosecond MOPA laser system.

Opt Express 2021 Jul;29(14):22008-22017

We demonstrate a sub-nanosecond MOPA system with a pulse repetition frequency of 1 kHz at 1.06 µm, based on an integrated seed source with pulse energy of 6.2 mJ and two conductively cooled end-pumped Nd:YAG slab gain modules. After a 4-pass amplification stage and a double-pass amplification stage with amplification factors of 12.6 dB and 5.84 dB, respectively, maximum pulse energy of 434 mJ with pulse duration of 691 ps was obtained, corresponding to a peak power of 628 MW. Via adjusting the pump distribution to compensate the static wavefront distortion of the signal laser, the beam quality, at the maximum pulse energy, was optimized to be 2.5 mm·mrad and 2.2 mm·mrad respectively in the vertical and transverse directions. The results benefit a variety of applications including material processing, nonlinear frequency conversion, and lidars.
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http://dx.doi.org/10.1364/OE.432018DOI Listing
July 2021

A "Two-Birds-One-Stone" Approach toward the Design of Bifunctional Human Immunodeficiency Virus Type 1 Entry Inhibitors Targeting the CCR5 Coreceptor and gp41 N-Terminal Heptad Repeat Region.

J Med Chem 2021 Jul 15. Epub 2021 Jul 15.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, 131 Dong An Road, Shanghai 200032, China.

Previous studies have reported the stepwise nature of human immunodeficiency virus type 1 (HIV-1) entry and the pivotal role of coreceptor CCR5 and the gp41 N-terminal heptad repeat (NHR) region in this event. With this in mind, we herein report a dual-targeted drug compound featuring bifunctional entry inhibitors, consisting of a piperidine-4-carboxamide-based CCR5 antagonist, TAK-220, and a gp41 NHR-targeting fusion-inhibitory peptide, C34. The resultant chimeras were constructed by linking both pharmacophores with a polyethylene glycol spacer. One chimera, CP12TAK, exhibited exceptionally potent antiviral activity, about 40- and 306-fold over that of its parent inhibitors, C34 and TAK-220, respectively. In addition to R5-tropic viruses, CP12TAK also strongly inhibited infection of X4-tropic HIV-1 strains. These data are promising for the further development of CP12TAK as a new anti-HIV-1 drug. Results show that this strategy could be extended to the design of therapies against infection of other enveloped viruses.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00781DOI Listing
July 2021
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