Publications by authors named "Zhen Wang"

4,389 Publications

  • Page 1 of 1

Fragment hopping protocol for the design of small-molecule protein-protein interaction inhibitors.

Bioorg Med Chem 2022 Jun 18;69:116879. Epub 2022 Jun 18.

Drug Discovery Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, United States; Department of Chemistry, University of South Florida, Tampa, FL 33620, United States. Electronic address:

Fragment-based ligand discovery (FBLD) is one of the most successful approaches to designing small-molecule protein-protein interaction (PPI) inhibitors. The incorporation of computational tools to FBLD allows the exploration of chemical space in a time- and cost-efficient manner. Herein, a computational protocol for the development of small-molecule PPI inhibitors using fragment hopping, a fragment-based de novo design approach, is described and a case study is presented to illustrate the efficiency of this protocol. Fragment hopping facilitates the design of PPI inhibitors from scratch solely based on key binding features in the PPI complex structure. This approach is an open system that enables the inclusion of different state-of-the-art programs and softwares to improve its performances.
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http://dx.doi.org/10.1016/j.bmc.2022.116879DOI Listing
June 2022

SARS-CoV-2 Accessory Protein ORF8 Decreases Antibody-Dependent Cellular Cytotoxicity.

Viruses 2022 Jun 7;14(6). Epub 2022 Jun 7.

Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.

Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. This decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.
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http://dx.doi.org/10.3390/v14061237DOI Listing
June 2022

Vibration Energy Harvesting from the Subwavelength Interface State of a Topological Metamaterial Beam.

Micromachines (Basel) 2022 May 30;13(6). Epub 2022 May 30.

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

Topological metamaterial has been a research hotpot in both physics and engineering due to its unique ability of wave manipulation. The topological interface state, which can efficiently and robustly centralize the elastic wave energy, is promising to attain high-performance energy harvesting. Since most of environmental vibration energy is in low frequency range, the interface state is required to be designed at subwavelength range. To this end, this paper developed a topological metamaterial beam with local resonators and studied its energy-harvesting performance. First, the unit cell of this topological metamaterial beam consists of a host beam with two pairs of parasitic beams with tip mass. Then, the band structure and topological features are determined. It is revealed that by tuning the distance between these two pairs of parasitic beams, band inversion where topological features inverse can be obtained. Then, two sub-chains, their design based on two topologically distinct unit cells, are assembled together with a piezoelectric transducer placed at the conjunction, yielding the locally resonant, topological, metamaterial, beam-based piezoelectric energy harvester. After that, its transmittance property and output power were obtained by using the frequency domain analysis of COMSOL Multiphysics. It is clear that the subwavelength interface state is obtained at the band-folding bandgap. Meanwhile, in the interface state, elastic wave energy is successfully centralized at the conjunction. From the response distribution, it is found that the maximum response takes place on the parasitic beam rather than the host beam. Therefore, the piezoelectric transducer is recommended to be placed on the parasitic beam rather than host beam. Finally, the robustness of the topological interface state and its potential advantages on energy harvesting were studied by introducing a local defect. It is clear that in the interface state, the maximum response is always located at the conjunction regardless of the defect degree and location. In other words, the piezoelectric transducer placed at the conjunction can maintain a stable and high-efficiency output power in the interface state, which makes the whole system very reliable in practical implementation.
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http://dx.doi.org/10.3390/mi13060862DOI Listing
May 2022

Experimental Investigation of Special-Shaped Concrete-Filled Square Steel Tube Composite Columns with Steel Hoops under Axial Loads.

Materials (Basel) 2022 Jun 13;15(12). Epub 2022 Jun 13.

School of Civil Engineering, Shandong Jianzhu University, Jinan 250101, China.

Special-shaped concrete-filled steel tube (SS-CFST) columns can be embedded in the wall, thus preventing the columns from protruding. This feature makes it popular in steel residential buildings. This paper proposes a new special-shaped concrete-filled square steel tube (SS-CFSST) composite column composed of multiple square steel tubes connected by steel hoops to form L-, T- or cross-shaped sections. Eight specimens were tested under axial loads with section shape, construction method, slenderness ratio, steel tube thickness, and steel strength as variation parameters. The structural performance, such as failure modes, peak load, load-displacement curves, load-strain curves, and Poisson's ratio of the steel tubes, were analyzed. The tests illustrated that the failure modes of hoop-type specimens and weld-type stub columns were mainly the local buckling of steel tubes and bending failure, and those of the weld-type slender columns were mainly overall bending failure. The load-carrying capacity of the hoop-type specimen was higher than that of the weld-type specimen with the same cross-sectional dimensions and slenderness ratio. Next, the stress-strain relationship model of core concrete in the SS-CFSST composite column was established by considering the restraint effect of the connection coincidence area of steel tubes and steel hoops on concrete. Additionally, the finite element model (FEM) of the column was established using this constitutive model. By comparing the failure modes, load-strain curves and bearing capacities obtained from the tests and FEM, the established FEM can accurately evaluate the mechanical properties of SS-CFSST composite columns with steel hoops under axial compression.
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http://dx.doi.org/10.3390/ma15124179DOI Listing
June 2022

Population Structure and Genetic Diversity of Chinese Honeybee () in Central China.

Genes (Basel) 2022 Jun 2;13(6). Epub 2022 Jun 2.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education & College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Central China has a rich terrain with a temperate monsoon climate and varied natural environments for the Chinese honeybee (). However, little comprehensive research on population genetic diversity has been done in this area. A population survey of the structure and genetic diversity of in this area is deeply needed for understanding adaptation to variable environments and providing more references for the protection of honeybee biodiversity. In this study, we present a dataset of 72 populations of Chinese honeybees collected from nine sites by whole genome sequencing in Central China. We obtained 2,790,214,878 clean reads with an average covering a depth of 22×. A total of 27,361,052 single nucleotide polymorphisms (SNPs) were obtained by mapping to the reference genome with an average mapping rate of 93.03%. Genetic evolution analysis was presented via the population structure and genetic diversity based on the datasets of SNPs. It showed that in plains exhibited higher genetic diversity than in mountain areas. The mantel test between groups revealed that some physical obstacles, especially the overurbanization of the plains, contributed to the differentiation. This study is conducive to elucidating the evolution of in different environments and provides a theoretical basis for investigating and protecting the Chinese honeybee.
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http://dx.doi.org/10.3390/genes13061007DOI Listing
June 2022

and Modules Are Related to Antler Growth Rate Revealed by Integrated Analyses of Genomics and Transcriptomics.

Animals (Basel) 2022 Jun 11;12(12). Epub 2022 Jun 11.

Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, China.

Deer antlers are organs of bone and have an extremely rapid growth rate. Thus far, the molecular mechanism underlying rapid antler growth has not been properly elucidated, and key genes driving this growth rate have not been fully identified. In this study, based on the newly assembled high-quality sika deer genome, we conducted an integrated analysis of genome-wide association analysis (GWAS) and weighted gene co-expression network analysis (WGCNA) using genome resequencing data from our previous GWAS, with weight and transcriptome sequencing data of faster- vs. slower-growing antlers of sika deer. The expressions of key genes were verified using Fragments Per Kilobase of transcript per Million fragments mapped (FPKM) in different tissue zones of the antler growth center, different types of sika deer tissues and antler tissues collected from faster and slower growth rates. The results show that a total of 49 genes related to antler growth rate were identified, and most of those genes were enriched in the and modules. The gene regulation network of antler growth rate through the pathway was constructed. In conclusion, the integration of GWAS and WGCNA analyses had great advantages in identifying regulatory genes of complex antler growth traits over using singular methods individually, and we believe that our findings in the present study can provide further insight into unveiling the mechanism underlying extraordinary fast antler growth rate in particular, as well as the regulatory mechanism of rapid tissue proliferation in general.
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http://dx.doi.org/10.3390/ani12121522DOI Listing
June 2022

Di-n-butyl phthalate negatively affects humic acid conversion and microbial enzymatic dynamics during composting.

J Hazard Mater 2022 Aug 6;436:129306. Epub 2022 Jun 6.

Technical Centre for Soil, Agriculture and Rural Ecology and Environment, Ministry of Ecology and Environment, Beijing 100012, China. Electronic address:

To understand the effects of phthalic acid esters (PAEs) on humic acid (HA) conversion, enzymatic and specific metabolic dynamics during composting under di-n-butyl phthalate (DBP) stress were evaluated for the first time. The results indicated that HA conversion was mainly related to bacteria rather than fungi, with positive associations with Actinobacteria, Chloroflexi, and Gemmatimonadota (all P < 0.05), and negative associations with Proteobacteria and Bacteroidota (all P < 0.05), while DBP stress retarded HA formation by altering the core microbes related to HA formation and their metabolic functions. Moreover, typical hydrolase and oxidoreductase activities were altered under DBP stress, proteases and cellulases were hindered, and peroxidases as well as polyphenol oxidases were promoted during composting. Overall, our data shows that DBP stress can retard HA formation and compost maturation by interfering with microbial activity. This study provides potentially useful information for the degradation and reuse of PAE-contaminated waste.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129306DOI Listing
August 2022

Composition and phase engineering of metal chalcogenides and phosphorous chalcogenides.

Nat Mater 2022 Jun 23. Epub 2022 Jun 23.

School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.

Two-dimensional (2D) materials with multiphase, multielement crystals such as transition metal chalcogenides (TMCs) (based on V, Cr, Mn, Fe, Cd, Pt and Pd) and transition metal phosphorous chalcogenides (TMPCs) offer a unique platform to explore novel physical phenomena. However, the synthesis of a single-phase/single-composition crystal of these 2D materials via chemical vapour deposition is still challenging. Here we unravel a competitive-chemical-reaction-based growth mechanism to manipulate the nucleation and growth rate. Based on the growth mechanism, 67 types of TMCs and TMPCs with a defined phase, controllable structure and tunable component can be realized. The ferromagnetism and superconductivity in FeX can be tuned by the y value, such as superconductivity observed in FeX and ferromagnetism in FeS monolayers, demonstrating the high quality of as-grown 2D materials. This work paves the way for the multidisciplinary exploration of 2D TMPCs and TMCs with unique properties.
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http://dx.doi.org/10.1038/s41563-022-01291-5DOI Listing
June 2022

A Liquid Metal-Enhanced Wearable Thermoelectric Generator.

Bioengineering (Basel) 2022 Jun 14;9(6). Epub 2022 Jun 14.

State Grid Jiangsu Electric Power Co., Ltd. Research Institute, Nanjing 211103, China.

It is a key challenge to continuously power personal wearable health monitoring systems. This paper reports a novel liquid metal-enhanced wearable thermoelectric generator (LM-WTEG that directly converts body heat into electricity for powering the wearable sensor system. The gallium-based liquid metal alloys with room-temperature melting point (24~30 °C) and high latent heat density (about 500 MJ/m) are used to design a new flexible finned heat sink, which not only absorbs the heat through the solid-liquid phase change of the LM and enhances the heat release to the ambient air due to its high thermal conduction. The LM finned is integrated with WTEG to present high biaxial flexibility, which could be tightly in contact with the skin. The LM-WTEG could achieve a super high output power density of 275 μW/cm for the simulated heat source (37 °C) with the natural convective heat transfer condition. The energy management unit, the multi-parameter sensors (including temperature, humidity, and accelerometer), and Bluetooth module with a total energy consumption of about 65 μW are designed, which are fully powered from LM-WTEG through harvesting body heat.
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http://dx.doi.org/10.3390/bioengineering9060254DOI Listing
June 2022

Impact of allograft types on outcomes after pediatric liver transplantation due to biliary atresia.

Pediatr Transplant 2022 Jun 23:e14342. Epub 2022 Jun 23.

Department of Pediatric transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China.

Background: Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes.

Methods: We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019.

Results: A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole-liver-transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow-up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss.

Conclusions: The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used.
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http://dx.doi.org/10.1111/petr.14342DOI Listing
June 2022

Investigations on the fish acute toxicity of fragrance ingredients, involving Chinese fish species and zebrafish embryos.

Environ Toxicol Chem 2022 Jun 23. Epub 2022 Jun 23.

School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, 510632, China.

While zebrafish (Danio rerio) has been accepted worldwide for evaluating chemical hazard to aquatic vertebrates, in some countries it is mandated to generate fish toxicity data using native species, such as Chinese rare minnow (Gobiocypris rarus) in China. This represents an additional regulatory constraint that may cause redundant tests, additional animal uses and higher costs. Previous studies showed that juvenile G. rarus was more sensitive than zebrafish juveniles and embryos to metals. To better understand the sensitivity of G. rarus to organic chemicals, we selected 29 fragrance ingredients belonging to various chemical classes and with differing physicochemical properties, for which good quality zebrafish acute toxicity data were available and tested them with juvenile G. rarus and embryo D. rerio using the OECD Test Guidelines. Chemical toxicity distribution (CTD) and chemical ratio distribution (CRD) models were established to systematically compare the sensitivity between juveniles of G. rarus and D. rerio, as well as between D. rerio embryos and juveniles. The results of CTD models showed that for tested chemicals, sensitivity of juvenile G. rarus was similar to that of D. rerio juveniles and embryos. The CRD comparisons revealed that juvenile G. rarus was slightly less sensitive by a factor of ~2 than juvenile D. rerio to ingredients belonging to Verhaar class 3 and ECOSAR ester class, while comparable to other chemicals. These comparative experiments demonstrated that fish toxicity data with G. rarus can be submitted for use in chemical registrations outside China, which would avoid repeating animal tests using D. rerio. Meanwhile, similar sensitivity of zebrafish juveniles and embryos to fragrance ingredients confirmed the suitability of replacing juveniles by zebrafish embryos. This article is protected by copyright. All rights reserved. © 2022 SETAC.
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http://dx.doi.org/10.1002/etc.5415DOI Listing
June 2022

Immuno-activated mesenchymal stem cell living electrospun nanofibers for promoting diabetic wound repair.

J Nanobiotechnology 2022 Jun 21;20(1):294. Epub 2022 Jun 21.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Diabetic wound is the leading cause of non-traumatic amputations in which oxidative stress and chronic inflammation are main factors affecting wound healing. Although mesenchymal stem cells (MSCs) as living materials can promote skin regeneration, they are still vulnerable to oxidative stress which limits their clinical applications. Herein, we have prepared (polylactic-co-glycolic acid) (PLGA) nanofibers electrospun with LPS/IFN-γ activated macrophage cell membrane. After defining physicochemical properties of the nanofibers modified by LPS/IFN-γ activated mouse RAW264.7 cell derived membrane (RCM-fibers), we demonstrated that the RCM-fibers improved BMMSC proliferation and keratinocyte migration upon oxidative stress in vitro. Moreover, bone marrow derived MSCs (BMMSCs)-loaded RCM-fibers (RCM-fiber-BMMSCs) accelerated wound closure accompanied by rapid re-epithelialization, collagen remodeling, antioxidant stress and angiogenesis in experimental diabetic wound healing in vivo. Transcriptome analysis revealed the upregulation of genes related to wound healing in BMMSCs when co-cultured with the RCM-fibers. Enhanced healing capacity of RCM-fiber-BMMSCs living material was partially mediated through CD200-CD200R interaction. Similarly, LPS/IFN-γ activated THP-1 cell membrane coated nanofibers (TCM-fibers) exhibited similar improvement of human BMMSCs (hBMMSCs) on diabetic wound healing in vivo. Our results thus demonstrate that LPS/IFN-γ activated macrophage cell membrane-modified nanofibers can in situ immunostimulate the biofunctions of BMMSCs, making this novel living material promising in wound repair of human diabetes.
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http://dx.doi.org/10.1186/s12951-022-01503-9DOI Listing
June 2022

Kir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters.

Nat Commun 2022 Jun 21;13(1):3544. Epub 2022 Jun 21.

Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, P. R. China.

Immunometabolism contributes to inflammation, but how activated macrophages acquire extracellular nutrients to fuel inflammation is largely unknown. Here, we show that the plasma membrane potential (V) of macrophages mediated by Kir2.1, an inwardly-rectifying K channel, is an important determinant of nutrient acquisition and subsequent metabolic reprogramming promoting inflammation. In the absence of Kir2.1 activity, depolarized macrophage V lead to a caloric restriction state by limiting nutrient uptake and concomitant adaptations in nutrient conservation inducing autophagy, AMPK (Adenosine 5'-monophosphate-activated protein kinase), and GCN2 (General control nonderepressible 2), which subsequently depletes epigenetic substrates feeding histone methylation at loci of a cluster of metabolism-responsive inflammatory genes, thereby suppressing their transcription. Kir2.1-mediated V supports nutrient uptake by facilitating cell-surface retention of nutrient transporters such as 4F2hc and GLUT1 by its modulation of plasma membrane phospholipid dynamics. Pharmacological targeting of Kir2.1 alleviated inflammation triggered by LPS or bacterial infection in a sepsis model and sterile inflammation in human samples. These findings identify an ionic control of macrophage activation and advance our understanding of the immunomodulatory properties of V that links nutrient inputs to inflammatory diseases.
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http://dx.doi.org/10.1038/s41467-022-31149-yDOI Listing
June 2022

Design, synthesis and bioactivity evaluation of favorable evodiamine derivative scaffold for developing cancer therapy.

Eur J Med Chem 2022 Jun 15;239:114530. Epub 2022 Jun 15.

School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address:

Natural product evodiamine is one of the most privileged scaffolds in drug discovery and is suitable for derivatization, which can be conducted quickly for structure optimization and structure-activity relationship research. In this work, a comprehensive SAR study on evodiamine scaffold with N14-3'-fluorophenyl substituted was completed, and compounds with high anti-tumor activity and good inhibitory effect on Top1 and Top2 were screened out. Tested evodiamine derivatives exhibited excellent broad-spectrum anti-tumor activity. Among them, compound 8b revealed 55.15% and 55.50% inhibition for Top1 and Top2 at 25 μM, as well as 0.16 and 0.13 μM IC value for MGC-803 and SGC-7901 cells, respectively; compound 9a revealed 70.50% and 71.81% inhibition for Top1 and Top2 at 25 μM, as well as 0.22 and 0.27 μM IC value for MGC-803 and SGC-7901 cells, respectively. The further biological evaluation showed that they could functionally induce apoptosis, significantly arrest the cell cycle at the G2/M phase, and markedly inhibit cell proliferation, migration and invasion. In addition, compound 9a performed a tumor inhibitory rate of 36.35% and showed no apparent toxicity in vivo. Overall, these optimized protocols will advance the progression of cancer chemotherapy and can be used to expand the options for screening therapeutic cancer drugs.
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http://dx.doi.org/10.1016/j.ejmech.2022.114530DOI Listing
June 2022

A Highly Selective Fluorescent Probe for the Detection of Nitroreductase Based on a Naphthalimide Scaffold.

J Fluoresc 2022 Jun 21. Epub 2022 Jun 21.

College of Chemistry and Chemical Engineering, Linyi University, Shandong, 276005, People's Republic of China.

The development of fluorescent probes for nitroreductase (NTR) has received intense attention because of its biological significance and wide application. In this work, a novel fluorescent probe for the detection of NTR in aqueous solution was designed and synthesized on a 1,8-naphthalimide scaffold. In the presence of NTR and nicotinamide adenine dinucleotide (NADH) under physiological conditions, the probe was converted into a 4-hydroxy-1,8-naphthalimide derivative and exhibited a sharp fluorescence enhancement at 550 nm, with a high selectivity for NTR over various analytes. The detection limit for NTR was determined to be 9.8 ng/ml by this probe. Due to its low signal background, this probe showed > 70-fold fluorescence enhancement. Theoretical calculations revealed that the reason for the fluorescence quenching of this probe is the photoinduced electron transfer (PET) from both the nitrobenzene and morpholine groups to the naphthalimide fluorophore.
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http://dx.doi.org/10.1007/s10895-022-02974-7DOI Listing
June 2022

Biofunctionalized graphene oxide nanosheet for amplifying antitumor therapy: Multimodal high drug encapsulation, prolonged hyperthermal window, and deep-site burst drug release.

Biomaterials 2022 Jun 9;287:121629. Epub 2022 Jun 9.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address:

Biofunctional surface-modification surpassed critical limitation of graphene oxide (GO) in biocompatibility and drug delivery efficiency, contributing to versatile biomedical applications. Here, a protein corona-bridged GO nanoplatform with high drug loading, longstanding hyperthermia, and controllable drug release, was engineered for amplified tumor therapeutic benefits. Structurally, GO surface was installed with phenylboronic acid (PBA) layer, on which iRGD conjugated apolipoprotein A-I (iRGD-apoA-I) was coordinated via boron electron-deficiency, to form the sandwich-like GO nanosheet (iAPG). The GO camouflaging by iRGD-apoA-I corona provided multimodal high doxorubicin (DOX) loading by π-π stacking and coordination, and generated a higher photothermal transformation efficiency simultaneously. In vitro studies demonstrated that iAPG significantly improved drug penetration and internalization, then achieved tumor-targeted DOX release through near-infrared (NIR) controlled endo/lysosome disruption. Moreover, iAPG mediated site-specific drug shuttling to produce a 3.53-fold enhancement of tumor drug-accumulation compared to the free DOX in vivo, and induced deep tumor penetration dramatically. Primary tumor ablation and spontaneous metastasis inhibition were further demonstrated with negligible side effects under optimal NIR. Taken together, our work provided multifunctional protein corona strategy to inorganic nanomaterials toward advantageous biomedical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121629DOI Listing
June 2022

Deconvoluting the Optical Response of Biocompatible Photonic Pigments.

Angew Chem Int Ed Engl 2022 Jun 20. Epub 2022 Jun 20.

Cambridge University: University of Cambridge, Chemistry Department, Lensfield Road, CB2 1EW, Cambridge, UNITED KINGDOM.

To unlock the widespread use of block copolymers as photonic pigments, there is an urgent need to consider their environmental impact (cf microplastic pollution). Here we show how an inverse photonic glass architecture can enable the use of biocompatible bottlebrush block copolymers (BBCPs), which otherwise lack the refractive index contrast needed for a strong photonic response. A library of photonic pigments is produced from poly(norbornene-graft-polycaprolactone)-block-poly(norbornene-graft-polyethylene glycol), with the color tuned via either the BBCP molecular weight or the processing temperature upon microparticle fabrication. The structure-optic relationship between the 3D porous morphology of the microparticles and their complex optical response is revealed by both an analytical scattering model and 3D finite-difference time domain (FDTD) simulations. Combined, this allows for strategies to enhance the color purity to be proposed and realized with our biocompatible BBCP system.
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http://dx.doi.org/10.1002/anie.202206562DOI Listing
June 2022

Effects of Incontro, Alleanza, Responsabilita, Autonomia Intervention Model Combined with Orem Self-Care Model and the Use of Smart Wearable Devices on Perceived Stress and Self-Efficacy in Patients after Total Hip Arthroplasty.

Comput Intell Neurosci 2022 9;2022:5780084. Epub 2022 Jun 9.

Medical College of Yangzhou University, Yangzhou, Jiangsu Province 225009, China.

Objective: To explore the effects of Incontro, Alleanza, Responsabilita, Autonomia (IARA) combined with Orem self-care model and the use of smart wearable devices on perceived stress and self-efficacy in patients after total hip arthroplasty (THA).

Methods: A total of 60 patients after THA in our hospital were enrolled. Patients were randomly divided into control group (IARA intervention model combined with Orem self-care model) and study group (intelligent wearable device combined conference-IARA and Orem self-care model). Harris hip function score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, functional independence measure (FIM) score, social support level, perceived stress, and self-efficacy were compared between the two groups.

Results: Harris hip function score, WOMAC score, FIM score, and the level of social support of the study group were higher compared with the control group after operation ( < 0.05). Additionally, the perceptual pressure in the study group was lower compared with the control group after intervention ( < 0.05). The self-efficacy of the two groups was compared, and the self-efficacy of the study group was higher than that of the control group at 4, 6, 8, and 12 weeks after the intervention, and the difference was statistically significant ( < 0.05).

Conclusion: Patients after THA utilize an intelligent wearable device combined with IARA model and Orem self-care model, which can effectively reduce awareness pressure, improve self-efficacy, and facilitate the improvement of the hip fracture.
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http://dx.doi.org/10.1155/2022/5780084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203192PMC
June 2022

RAD-Seq-Based High-Density Linkage Maps Construction and Quantitative Trait Loci Mapping of Flowering Time Trait in Alfalfa ( L.).

Front Plant Sci 2022 26;13:899681. Epub 2022 May 26.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Alfalfa ( L.) is a perennial forage crop known as the "Queen of Forages." To dissect the genetic mechanism of flowering time (FT) in alfalfa, high-density linkage maps were constructed for both parents of an F1 mapping population derived from a cross between Cangzhou (P1) and ZhongmuNO.1 (P2), consisting of 150 progenies. The FT showed a transgressive segregation pattern in the mapping population. A total of 13,773 single-nucleotide polymorphism markers was obtained by using restriction-site associated DNA sequencing and distributed on 64 linkage groups, with a total length of 3,780.49 and 4,113.45 cM and an average marker interval of 0.58 and 0.59 cM for P1 and P2 parent, respectively. Quantitative trait loci (QTL) analyses were performed using the least square means of each year as well as the best linear unbiased prediction values across 4 years. Sixteen QTLs for FT were detected for P1 and 22 QTLs for P2, accounting for 1.40-16.04% of FT variation. RNA-Seq analysis at three flowering stages identified 5,039, 7,058, and 7,996 genes that were differentially expressed between two parents, respectively. Based on QTL mapping, DEGs analysis, and functional annotation, seven candidate genes associated with flowering time were finally detected. This study discovered QTLs and candidate genes for alfalfa FT, making it a useful resource for breeding studies on this essential crop.
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http://dx.doi.org/10.3389/fpls.2022.899681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199863PMC
May 2022

Rapeseed () Mitogen-Activated Protein Kinase 1 Enhances Shading Tolerance by Regulating the Photosynthesis Capability of Photosystem II.

Front Plant Sci 2022 2;13:902989. Epub 2022 Jun 2.

Engineering Research Center for Rapeseed, College of Agronomy and Biotechnology, Southwest University, Chongqing, China.

Rapeseed () is the third-largest source of vegetable oil in the world with an edible, medicinal, and ornamental value. However, insufficient light or high planting density directly affects its growth, development, yield, and quality. Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases that play key roles in regulating the responses to biotic and abiotic stresses in plants. In this study, we found that the promoter of contained several light-responsive elements (including the AT1-motif, G-Box, and TCT-motif), consistent with its shading stress-induced upregulation. Compared with the wild type under shading stress, -overexpressing plants showed higher light capture efficiency and carbon assimilation capacity, enhancing their shading tolerance. Using RNA sequencing, we systematically investigated the function of in shading stress on photosynthetic structure, Calvin cycle, and light-driven electron transport. Notably, numerous genes encoding light-harvesting chlorophyll a/b-binding proteins (BnaLHCBs) in photosystem II-light-harvesting complex (LHC) II supercomplex were significantly downregulated in the -overexpressing lines relative to the wild type under shading stress. Combining RNA sequencing and yeast library screening, a candidate interaction partner of BnaMAPK1 regulating in shading stress, BnaLHCB3, was obtained. Moreover, yeast two-hybrid and split-luciferase complementation assays confirmed the physical interaction relationship between BnaLHCB3 and BnaMAPK1, suggesting that BnaMAPK1 may involve in stabilizing the photosystem II-LHC II supercomplex. Taken together, our results demonstrate that positively regulates photosynthesis capability to respond to shading stress in rapeseed, possibly by controlling antenna proteins complex in photosystem II, and could provide valuable information for further breeding for rapeseed stress tolerance.
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http://dx.doi.org/10.3389/fpls.2022.902989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201689PMC
June 2022

A new thermosensor from rice.

Mol Plant 2022 Jun 18. Epub 2022 Jun 18.

State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

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http://dx.doi.org/10.1016/j.molp.2022.06.008DOI Listing
June 2022

Prophylactic use of ramelteon for delirium in hospitalized patients: A systematic review and meta-analyses.

J Acad Consult Liaison Psychiatry 2022 Jun 16. Epub 2022 Jun 16.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN; Center for Sleep Medicine, Mayo Clinic, Rochester, MN. Electronic address:

Objective: Small prospective studies, case reports, as well as some randomized placebo-controlled trials and previous meta-analyses have shown that ramelteon, a melatonin agonist, may reduce the risk of developing delirium. The goal of this systemic review and meta-analyses was to assess the current evidence supporting the use of ramelteon in delirium prevention by including data from larger (> 100 subjects) and more recent trials since the most recent meta-analyses were published in 2019. There were no exclusions for trial size, age, ramelteon dose, length of treatment, or hospital setting.

Methods: Medline, Embase, PsycINFO, EBM Reviews, Scopus, and Web of Science databases were queried using the search terms delirium (with sub-terms including prevention and control), ramelteon, Rozerem or melatonin receptor agonists, for English-language publications until March 16, 2021. Randomized placebo-controlled trials of hospitalized subjects receiving ramelteon for delirium prevention were included. The primary outcome of interest was delirium incidence. Odds ratios (ORs) of the risk of developing incident delirium and 95%-confidence intervals (CIs) were calculated using a random effects model.

Results: A total of 177 articles were identified by the literature search. Five studies (n = 443, 53.7% male) met criteria for inclusion in the final meta-analyses. The meta-analyses of the randomized placebo-controlled trials revealed that ramelteon did not result in a reduction in the risk of incident delirium (n = 443; OR = 0.49; 95% CI = 0.13 to 1.85). A moderate degree of heterogeneity was noted among the studies (I = 53%).

Conclusions: Current evidence suggests that ramelteon is ineffective as a prophylactic drug in reducing the incidence of delirium in hospitalized patients.
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http://dx.doi.org/10.1016/j.jaclp.2022.06.002DOI Listing
June 2022

Outcome of Split Liver Transplantation from Pediatric Donors Weighing 25 kg or Less.

Liver Transpl 2022 Jun 17. Epub 2022 Jun 17.

Organ Transplantation Center, Tianjin, Tianjin, China.

The lower limit of body weight for "splitable" liver grafts remains unknown. To examine the outcome of split liver transplantation (SLT) from pediatric donors ≤ 25 kg relative to conventional graft type liver transplantation from deceased donors under corresponding conditions, a total of 158 patients who received primary liver transplantation, including 22 SLTs from donors ≤ 25 kg, 46 SLTs from donors > 25 kg, 76 whole liver transplantations (WLTs) and 14 reduced liver transplantations (RLTs) in donors ≤ 25 kg, between January 2018 and December 2019 were included in the study. There was no significant difference in the complications, patient survival and graft survival between each of the latter three groups and SLT ≤ 25 kg group. Pediatric end-stage liver disease (PELD) score was the independent predictor of graft loss (death or retransplantation). Graft weight was the independent predictor of hepatic artery thrombosis (HAT). SLT using well-selected pediatric donors ≤ 25 kg is an effective strategy to increase organ availability, especially for low body weight recipients, compared with conventional graft type from deceased donors under the condition of corresponding donor weight without increasing morbidity and mortality.
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http://dx.doi.org/10.1002/lt.26530DOI Listing
June 2022

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma.

Front Cell Dev Biol 2022 30;10:799459. Epub 2022 May 30.

The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.

N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms and is an important posttranscriptional mechanism for regulating genes. In previous research, we found that m6A regulator-mediated RNA methylation modification was involved in asthma; however, the specific modified genes are not clear. In this study, we systematically evaluated the transcriptome-wide m6A methylome and m6A-modified genes in asthma. Here, we performed two high-throughput sequencing methods, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and RNA sequencing (RNA-seq) to identify key genes with m6A modification in asthma. Through difference analysis, we found that 416 methylation peaks were significantly upregulated and 152 methylation peaks were significantly downregulated, and it was mainly distributed in 3' UTR. Furthermore, compared with the control group, there were 2,505 significantly upregulated genes and 4,715 significantly downregulated genes in the asthma group. Next, through a combined analysis of transcriptome and differential peaks, 14 differentially expressed genes related to RNA methylation modification were screened. Finally, through 87 health controls and 411 asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) program, we verified three m6A-modified key genes (BCL11A, MATK, and CD300A) and found that they were mainly distributed in exons and enriched in 3' UTR. Our findings suggested that intervening in m6A-modified genes may provide a new idea for the treatment of asthma.
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http://dx.doi.org/10.3389/fcell.2022.799459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197130PMC
May 2022

The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion.

J Cancer 2022 9;13(8):2477-2489. Epub 2022 May 9.

Department of Oncology, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.

Hepatocellular carcinoma (HCC) is a major type of death-causing cancer whose pathological mechanisms are not fully understood. In addition, the identification of effective biomarkers for HCC prognosis is in emergency. Although a variety of studies have shown that Complement C11 binding protein (C1QBP) may play a tumor-promoting or tumor-suppressive role in cancer, the functions and mechanisms of C1QBP in HCC progression are under-investigating. Bioinformatic approaches were employed for checking the expression of in HCC patient samples and the association between mRNA expression and survival rates of patients with HCC or the promoter methylation of . MTT analysis, PI/Annexin V staining, transwell and metabolic flux assays were performed to examine the effects of C1QBP on proliferation, apoptosis, migration, invasion, and oxidative phosphorylation of HCC cells. In the present study, we observed that is lower expressed in HCC samples and cell lines. Moreover, high levels of were associated with unfavorable outcomes of HCC patients. Loss-of-function assays showed that proliferation, migration and invasion of HCC cells were mitigated while cell apoptosis was augmented upon the loos of C1QBP. Moreover, the oxidative phosphorylation was moderately decreased when C1QBP was depleted. Furthermore, we also investigated the methylation status and copy number variation of and analyzed their correlation with its mRNA expression in HCC patients. Finally, we suggested that is correlated with genes encoding ribosome RPL-related proteins and mitochondrial MRPL-related proteins in HCC patients. is correlated with a poor prognosis of HCC patients and promotes the survival, migration and invasion of HCC cells.
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http://dx.doi.org/10.7150/jca.69379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174857PMC
May 2022

Construction of a novel radiosensitivity- and ferroptosis-associated gene signature for prognosis prediction in gliomas.

J Cancer 2022 20;13(8):2683-2693. Epub 2022 May 20.

Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing 210029, China.

Gliomas are the most refractory intracranial disease characterized by high incidence and mortality rates. Therefore, radiotherapy plays a crucial role in the treatment of gliomas. However, recent evidence reveals that ferroptosis is highly associated with radiosensitivity in tumor cells. Therefore, this study aimed to investigate radiosensitivity- and ferroptosis-associated biomarkers. Moreover, the study aimed to provide new strategies for the treatment and evaluation of prognosis in gliomas. The mRNA sequencing and relevant clinical data were obtained from The Cancer Genome Atlas (TCGA). Secondly, differential analysis was conducted to reveal the radiosensitivity- and ferroptosis-associated differentially expressed genes (DEGs). Further, a predictive model based on the seven genes was constructed, and LASSO regression analysis was carried out. After that, the Chinese Glioma Genome Atlas (CGGA) was used for validation of the results. A total of 36 radiosensitivity- and 19 ferroptosis-associated DEGs with a prognostic value were identified. Moreover, seven intersecting genes (HSPB1, STAT3, CA9, MAP1LC3A, MAPK1, ZEB1, and TNFAIP3) were identified as the risk signature genes. The ROC curves and K-M analysis revealed that the signature genes showed a good survival prediction. Furthermore, the functional analysis revealed that the differentially expressed genes between the high-risk and the low-risk groups were enriched in glioma-related biological processes. In addition, differences were reported in immune function status between the two groups. This study revealed that the seven biomarkers could help predict the prognosis in glioma patients. In addition, this study provides a basis for understanding the molecular mechanisms of radiosensitivity and ferroptosis in the treatment of gliomas.
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http://dx.doi.org/10.7150/jca.72893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174846PMC
May 2022

The Incidence and Prevalence of Pulmonary Hypertension in the COPD Population: A Systematic Review and Meta-Analysis.

Int J Chron Obstruct Pulmon Dis 2022 10;17:1365-1379. Epub 2022 Jun 10.

Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China.

Purpose: Chronic obstructive pulmonary disease (COPD)-related pulmonary hypertension (PH) is one of the most common comorbidities of COPD, and often leads to a worse prognosis. Although the estimated prevalence and risk factors of COPD-related PH have been widely reported, these results have not been well integrated. This study aimed to review the worldwide incidence and prevalence of COPD-related PH and explore possible factors affecting its prevalence.

Patients And Methods: We searched four electronic databases (Web of Science, Embase, Cochrane, and MEDLINE) to identify all observational studies on the prevalence of COPD-related PH from database creation until July 20, 2021. Eligibility screening, quality assessment, and data extraction of the retrieved studies were independently conducted by two reviewers. Meta-analyses were performed to determine the prevalence of PH in the COPD population. Random-effects meta-regression model analyses were conducted to investigate the sources of heterogeneity.

Results: Altogether, 38 articles were included in the meta-analyses. The pooled prevalence was 39.2% (95% CI: 34.0-44.4, = 97.6%) for COPD-related PH. Subgroup analyses showed that the prevalence of PH increased with COPD severity, where the majority (30.2%) had mild PH and the minority had severe PH (7.2%). Furthermore, we found a significant regional difference in the prevalence of COPD-related PH ( = 0.000), which was the highest in Africa (64.0%) and the lowest in Europe (30.4%). However, stratified studies on other factors involving mean age, sex, enrolment time, participant recruitment settings, and PH diagnostic methods showed no significant differences in prevalence ( >0.05).

Conclusion: The global incidence of PH in the COPD population is very high, and there are significant regional and international variations. Patients with COPD should be screened for PH and contributing risk factors to reduce the burden on individuals and society.
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http://dx.doi.org/10.2147/COPD.S359873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196913PMC
June 2022

GDF-11 promotes human trophoblast cell invasion by increasing ID2-mediated MMP2 expression.

Cell Commun Signal 2022 Jun 15;20(1):89. Epub 2022 Jun 15.

Henan Key Laboratory of Reproduction and Genetics, Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, Henan, China.

Background: Growth differentiation factor-11 (GDF-11), also known as bone morphogenetic protein-11, belongs to the transforming growth factor-beta superfamily. GDF-11 was first identified as an important regulator during embryonic development. Increasing evidence has demonstrated that GDF-11 regulates the development of various organs and its aberrant expressions are associated with the risk of cardiovascular diseases and cancers. Extravillous trophoblast (EVT) cells invasion is a critical event for placenta development and needs to be finely regulated. However, to date, the biological function of GDF-11 in the human EVT cells remains unknown.

Methods: HTR-8/SVneo, a human EVT cell line, and primary cultures of human EVT cells were used to examine the effect of GDF-11 on matrix metalloproteinase 2 (MMP2) expression. Matrigel-coated transwell invasion assay was used to examine cell invasiveness. A series of in vitro experiments were applied to explore the underlying mechanisms that mediate the effect of GDF-11 on MMP2 expression and cell invasion.

Results: Treatment with GDF-11 stimulates MMP2 expression, in the HTR-8/SVneo and primary human EVT cells. Using a pharmacological inhibitor and siRNA-mediated knockdown approaches, our results demonstrated that the stimulatory effect of GDF-11 on MMP2 expression was mediated by the ALK4/5-SMAD2/3 signaling pathways. In addition, the expression of inhibitor of DNA-binding protein 2 (ID2) was upregulated by GDF-11 and that was required for the GDF-11-stimulated MMP2 expression and EVT cell invasion.

Conclusions: These findings discover a new biological function and underlying molecular mechanisms of GDF-11 in the regulation of human EVT cell invasion. Video Abstract.
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http://dx.doi.org/10.1186/s12964-022-00899-zDOI Listing
June 2022

The causal relationship between sleep traits and the risk of schizophrenia: a two-sample bidirectional Mendelian randomization study.

BMC Psychiatry 2022 Jun 15;22(1):399. Epub 2022 Jun 15.

Department of Cardiovascular Surgery, School of Medicine, the First Affiliated Hospital of Zhejiang University, Number 79 Qingchun Road, Hangzhou, China.

Background: Observational studies suggest that sleep disturbances are commonly associated with schizophrenia. However, it is uncertain whether this relationship is causal. To investigate the bidirectional causal relation between sleep traits and schizophrenia, we performed a two-sample bidirectional Mendelian randomization (MR) study with the fixed effects inverse-variance weighted (IVW) method.

Methods: As genetic variants for sleep traits, we selected variants from each meta-analysis of genome-wide association studies (GWASs) conducted using data from the UK Biobank (UKB).

Results: We found that morning diurnal preference was associated with a lower risk of schizophrenia, while long sleep duration and daytime napping were associated with a higher risk of schizophrenia. Multivariable MR analysis also showed that sleep duration was associated with a higher risk of schizophrenia after adjusting for other sleep traits. Furthermore, genetically predicted schizophrenia was negatively associated with morning diurnal preference and short sleep duration and was positively associated with daytime napping and long sleep duration.

Conclusions: Therefore, sleep traits were identified as a potential treatment target for patients with schizophrenia.
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http://dx.doi.org/10.1186/s12888-022-03946-8DOI Listing
June 2022
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