Publications by authors named "Han Wang"

1,836 Publications

  • Page 1 of 1

Trimethylamine N-oxide and its precursors in relation to blood pressure: A mendelian randomization study.

Front Cardiovasc Med 2022 22;9:922441. Epub 2022 Jul 22.

Department of Cardiology, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China.

Objective: Previous studies have demonstrated that trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and carnitine, are closely associated with blood pressure (BP) changes. Nevertheless, with the limitation of reverse causality and confounder in observational studies, such a relationship remains unclear. We aimed to assess the causal relationship of TMAO and its precursors with BP by the Mendelian Randomization (MR) approach.

Method: In this study, two-sample MR was used to reveal the causal effect of TMAO and its precursors on BP. Pooled data of TMAO and its precursors was from genome-wide association studies (GWAS) which includes summary data of human metabolome in 2,076 European participants from Framingham Heart Study. Summary-level data for BP was extracted from the International Consortium of Blood Pressure-Genome Wide Association Studies. Inverse variance weighted (IVW), MR Egger regression, Maximum likelihood, Weighted median, and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used in this MR analysis.

Results: A total of 160 independent SNP loci were associated with TMAO and three precursors, including 58 associated with TMAO, 29 associated with choline, 44 associated with betaine, and 29 associated with carnitine, were selected. MR results suggested that a 1 unit increase in TMAO should be associated with a 1SD increase in systolic BP mmHg (beta: 0.039, SE, 0.072, = 0.020). Additionally, our findings also indicated that a 1 unit increase in carnitine should be associated with a 1SD increase in systolic BP mmHg (beta: 0.055, SE: 0.075, = 0.039). This result was also confirmed by sensitivity analysis methods such as Maximum likelihood, MR-PRESSO, and Weighted median. No effects of betaine or choline on systolic or diastolic BP were observed in the present study.

Conclusion: Our study provides evidence of a causal relationship of TMAO and its precursors with BP, suggesting that mediating the generation of TMAO would be beneficial for lowering BP.
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http://dx.doi.org/10.3389/fcvm.2022.922441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354484PMC
July 2022

Functional analysis of differentially expressed long non-coding RNAs in DENV-3 infection and antibody-dependent enhancement of viral infection.

Virus Res 2022 Aug 4:198883. Epub 2022 Aug 4.

Institute of Medical Biology, Chinese academy of Medical Sciences & Peking Union Medical College, Kunming, PR China; Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, PR China; Yunnan Key Laboratory of Vector-borne Infectious Disease, Kunming, PR China. Electronic address:

Dengue fever, as a mosquito-borne viral disease widely spread in tropical and subtropical regions, remarkably threatens public health, while the mechanism involved in host-DENV interaction has not been fully elucidated. Firstly, we analyzed the expression levels of long non-coding RNAs (lncRNAs) in THP-1 cells after DENV-3 infection and Antibody- Dependent Enhancement of viral infection (ADE-VI) by RNA-Seq. Secondly, through the RT-qPCR to confirm those differentially expressed (DE) lncRNAs. Then, we also analyzed the competitive endogenous RNA (CeRNA) regulatory network of DE lncRNAs. Finally, we predicted the encode ability of DE lncRNAs. It was found that on the X and Y chromosomes, the expression levels of lncRNAs in THP-1 cells after ADE-VI were significantly different from those in the negative control and the DENV-3 infection groups. There were 71 DE lncRNAs after DENV-3 infection, including 42 up-regulated and 29 down-regulated lncRNAs. A total of 70 DE lncRNAs after ADE-VI were detected, including 38 up-regulated and 32 down- regulated lncRNAs. After ADE-VI and DENV-3 infection, there were 35 DE lncRNAs, including 11 up-regulated and 24 down-regulated lncRNAs. The analysis of the CeRNA regulatory network of DE lncRNAs revealed that, TRIM29, STC2, and IGFBP5 were correlated with the ADE-VI. Additionally, it was found that lncRNAs not only participated in the CeRNA regulatory network, but also maybe encoded small peptides. Our findings provided clues for further investigation into the lncRNAs associated antiviral mechanism of ADE-VI and DENV-3 infection.
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http://dx.doi.org/10.1016/j.virusres.2022.198883DOI Listing
August 2022

Quantitative acetylomics reveals dynamics of protein lysine acetylation in mouse livers during aging and upon the treatment of nicotinamide mononucleotide.

Mol Cell Proteomics 2022 Aug 3:100276. Epub 2022 Aug 3.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Hai Ke Rd., Pudong, Shanghai, 201210, China. Electronic address:

Lysine acetylation is a reversible and dynamic post-translational modification that play vital roles in regulating multiple cellular processes including aging. However, acetylome-wide analysis in the aging process remains poorly studied in mammalian tissues. Nicotinamide adenine dinucleotide (NAD), a hub metabolite, benefits healthspan at least in part due to the activation of Sirtuins, a family of NAD-consuming deacetylases, indicating changes in acetylome. Here, we combine two antibodies for the enrichment of acetylated peptides and perform label-free quantitative acetylomic analysis of mouse livers during natural aging and upon the treatment of beta-nicotinamide mononucleotide (NMN), a NAD booster. Our study describes previously unknown acetylation sites and reveals the acetylome-wide dynamics with age as well as upon the treatment of NMN. We discover protein acetylation events as potential aging biomarkers. We demonstrate that the life-beneficial effect of NMN could be partially reflected by the changes in age-related protein acetylation. Our quantitative assessment indicates that NMN has mild effects on acetylation sites previously reported as substrates of Sirtuins. Collectively, our data analyzes protein acetylation with age, laying critical foundation for the functional study of protein post-translational modification essential for healthy aging and perhaps disease conditions.
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http://dx.doi.org/10.1016/j.mcpro.2022.100276DOI Listing
August 2022

DP Compress: A Model Compression Scheme for Generating Efficient Deep Potential Models.

J Chem Theory Comput 2022 Aug 4. Epub 2022 Aug 4.

HEDPS, CAPT, College of Engineering, Peking University, Beijing 100871, P. R. China.

Machine-learning-based interatomic potential energy surface (PES) models are revolutionizing the field of molecular modeling. However, although much faster than electronic structure schemes, these models suffer from costly computations via deep neural networks to predict the energy and atomic forces, resulting in lower running efficiency as compared to the typical empirical force fields. Herein, we report a model compression scheme for boosting the performance of the Deep Potential (DP) model, a deep learning-based PES model. This scheme, we call DP Compress, is an efficient postprocessing step after the training of DP models (DP Train). DP Compress combines several DP-specific compression techniques, which typically speed up DP-based molecular dynamics simulations by an order of magnitude faster and consume an order of magnitude less memory. We demonstrate that DP Compress is sufficiently accurate by testing a variety of physical properties of Cu, HO, and Al-Cu-Mg systems. DP Compress applies to both CPU and GPU machines and is publicly available online.
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http://dx.doi.org/10.1021/acs.jctc.2c00102DOI Listing
August 2022

Targeting clock-controlled gene Nrf2 ameliorates inflammation-induced intervertebral disc degeneration.

Arthritis Res Ther 2022 08 3;24(1):181. Epub 2022 Aug 3.

Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.

Background: Intervertebral disc (IVD) is a highly rhythmic tissue, which experiences a diurnal cycle of high/low mechanical loading via the changes of activity/rest phase. There are signs that disruption of the peripheral IVD clock is related to the process of intervertebral disc degeneration (IDD). However, it is still unclear whether inflammation could disturb the IVD clock and thus induce the process of IDD.

Methods And Results: In this study, we used IL-1β, a commonly used inflammatory factor, to induce IDD and found that the IVD clock was dampened in degenerated human nucleus pulposus specimens, rat nucleus pulposus (NP) tissues, and cells. In this study, we found that the circadian clock of NP cells was totally disrupted by knockdown of the core clock gene brain and muscle arnt-like protein-1 (Bmal1), which thus induced the dysfunction of NP cells. Next, we explored the mechanism of dampened clock-induced IDD and found that knockdown of Bmal1 decreased the expression of nuclear factor erythroid2-related factor 2 (NRF2), a downstream target gene of Bmal1, and increased inflammatory response, oxidative stress reaction, and apoptosis of NP cells. In addition, NRF2 activation attenuated the dysfunction of NP cells induced by the dampened IVD clock and the degenerative process of NP tissues in an organotypic tissue-explant model.

Conclusions: Taken together, our study extends the relationship between peripheral clock and IVD homeostasis and provides a potential therapeutic method for the prevention and recovery of IDD by targeting the clock-controlled gene Nrf2.
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http://dx.doi.org/10.1186/s13075-022-02876-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347076PMC
August 2022

Programmable Birefringent Patterns from Modulating the Localized Orientation of Cellulose Nanocrystals.

ACS Appl Mater Interfaces 2022 Aug 2;14(31):36277-36286. Epub 2022 Aug 2.

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Birefringence has been attracting broad attention due to its strong potential for applications in biomedicine and optics, such as biomedical diagnosis, colorimetric sensing, retardant, and polarization encoding. However, engineering architectures with precisely controllable birefringence remains a challenge due to the lack of effective modulation of the localized orientation. Here, by taking advantage of the inherently one-dimensional (1D) anisotropic structure of cellulose nanocrystals (CNCs), we demonstrate an approach to tune the alignment of CNCs with a well-controllable orientation at localized preciseness, which is in contrast to the previously reported unidirectional/radical orientation of CNC-based birefringent structures. The localized modulation of CNC orientation is facilitated by directing the 1D nanocrystals to align along the template periphery and the migrated three-phase contact line during the evaporation. The resultant CNC films exhibit birefringent extinction patterns under polarized light, in which versatile pattern designs can be obtained by employing templates with different shapes and template arrays with varied layouts. Due to the locally modulated orientation of CNCs, the films indicate "kaleidoscope-like" dynamically transformable designs of the birefringent patterns depending on the polarized angle, which has barely been observed previously. Furthermore, an N-nary encoding system for abundant information storage is demonstrated based on the sunlight-transparent CNC films, but with visible extinction patterns under polarized light, which is promising for encryptions, anticounterfeiting, and imaging, enriching the attractive research area of bio-based photonics.
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http://dx.doi.org/10.1021/acsami.2c12205DOI Listing
August 2022

Leaf morphological traits as adaptations to multiple climate gradients.

J Ecol 2022 Jun 30;110(6):1344-1355. Epub 2022 Mar 30.

Department of Earth System Science, Ministry of Education Key Laboratory for Earth System Modeling Institute for Global Change Studies, Tsinghua University Beijing China.

Leaf morphological traits vary systematically along climatic gradients. However, recent studies in plant functional ecology have mainly analysed quantitative traits, while numerical models of species distributions and vegetation function have focused on traits associated with resource acquisition; both ignore the wider functional significance of leaf morphology.A dataset comprising 22 leaf morphological traits for 662 woody species from 92 sites, representing all biomes present in China, was subjected to multivariate analysis in order to identify leading dimensions of trait covariation (correspondence analysis), quantify climatic and phylogenetic contributions (canonical correspondence analysis with variation partitioning) and characterise co-occurring trait syndromes (-means clustering) and their climatic preferences.Three axes accounted for >20% of trait variation in both evergreen and deciduous species. Moisture index, precipitation seasonality and growing-season temperature explained 8%-10% of trait variation; family 15%-32%. Microphyll or larger, mid- to dark green leaves with drip tips in wetter climates contrasted with nanophyll or smaller glaucous leaves without drip tips in drier climates. Thick, entire leaves in less seasonal climates contrasted with thin, marginal dissected, aromatic and involute/revolute leaves in more seasonal climates. Thick, involute, hairy leaves in colder climates contrasted with thin leaves with marked surface structures (surface patterning) in warmer climates. Distinctive trait clusters were linked to the driest and most seasonal climates, for example the clustering of picophyll, fleshy and succulent leaves in the driest climates and leptophyll, linear, dissected, revolute or involute and aromatic leaves in regions with highly seasonal rainfall. Several trait clusters co-occurred in wetter climates, including clusters characterised by microphyll, moderately thick, patent and entire leaves or notophyll, waxy, dark green leaves. . The plastic response of size, shape, colour and other leaf morphological traits to climate is muted, thus their apparent shift along climate gradients reflects plant adaptations to environment at a community level as determined by species replacement. Information on leaf morphological traits, widely available in floras, could be used to strengthen predictive models of species distribution and vegetation function.
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http://dx.doi.org/10.1111/1365-2745.13873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313568PMC
June 2022

Decision Tree Algorithm for Visual Art Design in a Psychotherapy System for College Students.

Occup Ther Int 2022 14;2022:1255200. Epub 2022 Jul 14.

School of Computer Science and Technology, Huaibei Normal University, Huaibei, Anhui 235000, China.

With the development of society, psychological health becomes a basic standard for a college student to grow into a qualified person. This study is aimed at using data mining principles and methods to excavate the factors that lead to psychological problems of college students, to purposefully carry out psychological interventions, use visual art design methods to promote college students' psychological health treatment, and build a perfect system of college students' psychological treatment. Based on the theories of data mining, we built a data analysis model, elaborated the data preprocessing method, and applied the Apriori algorithm to analyze the data of obsessive-compulsive symptoms and interpersonal sensitivity symptoms, and various psychological problem attributes extracted the strong association rules and analyzed the results. Take advantage of the corresponding unique school environment and educational advantages, to build a set of mental health education methods suitable for modern college students, and truly enable them to obtain satisfactory psychological interventions in a reasonable art design treatment phase. Based on the above association pattern mining results, a series of preprocessing operations were performed on the data, and then, the Apriori algorithm was applied to discover the potential association relationships among 9 psychological dimension factors of college students, and then, the ID3 decision tree algorithm was used to construct a decision tree and pruning process, from which the classification rules of students' psychological problems were analyzed and discovered. These studies provide some practical reference basis for school counseling work.
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http://dx.doi.org/10.1155/2022/1255200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303154PMC
August 2022

Polylactic acid scaffold with directional porous structure for large-segment bone repair.

Int J Biol Macromol 2022 Jul 29;216:810-819. Epub 2022 Jul 29.

College of Materials Science and Engineering, Wuhan Textile University, Wuhan 430200, China; Key Laboratory of Green Processing and Functional New Textile Materials of Ministry of Education, Wuhan Textile University, Wuhan 430200, China. Electronic address:

Biodegradable porous scaffolds with different structure, porosity, and strength play a critical role in the repair and regeneration of defects in bone tissue engineering by changing the proliferation condition for cell. In this study, polylactic acid (PLA) scaffold with directional porous structure is designed and fabricated using the method of ice template and phase inversion for speeding up bone repair by promoting the growth and proliferation of bone cells. The morphology, mechanical properties, hydrophilicity, and wicking properties of PLA scaffolds were characterized by scanning electron microscope, universal testing machine, contact angle tester and wicking rate test, respectively. In vitro biocompatibility has been investigated through measuring cell adhesion, proliferation, and viability on PLA scaffold with directional porous structure. Prepared PLA scaffold was implanted into animals to observe the repair mechanism of large-sized bone defects. This study proposes a novel bioporous scaffold design to induce osteocyte growth at the rat calvaria with a directional pore structure, and the scaffold edges were integrated with the calvaria at week 12, effectively promoting the repair and regeneration of defective bone tissue.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.207DOI Listing
July 2022

An Optically Anisotropic Crystal with Large Birefringence Arising from Cooperative π Orbitals.

Angew Chem Int Ed Engl 2022 Jul 29. Epub 2022 Jul 29.

Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, State Key Laboratory of Structrual Chemistry, 155 Yangqiao Road West, 350002, 350002, Fuzhou, CHINA.

Birefringent materials are highly demanded for high-performance polarized optics. As compared with artificial anisotropic metamaterials, anisotropic crystals have advantages of low optical losses and easy processing, but their birefringence is still limited. Herein, based on first-principles studies, we identified a new type of functional anion units, (HxC6N9)(3-x)- (x = 0, 1, 2), and then successfully synthesized a new anisotropic crystal, namely, CsH2C6N9·H2O (I), whose crystal structure consists of (H2C6N9)- anions. Remarkably, I is ultraviolet transparent and exhibits very large birefringence of about [email protected] nm, which is much larger than those of commercial birefringent crystals. These results make I a candidate for highly efficient manipulation of optics and light in optical modulation devices. Theoretical calculations reveal that large birefringence mainly arises from the cooperative π orbitals in (H2C6N9)- anions. This work provides a new insight on the underlying structure-property relationships of anisotropic crystals.
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http://dx.doi.org/10.1002/anie.202208811DOI Listing
July 2022

The shaping of cancer genomes with the regional impact of mutation processes.

Exp Mol Med 2022 Jul 28;54(7):1049-1060. Epub 2022 Jul 28.

Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Mutation signature analysis has been used to infer the contributions of various DNA mutagenic-repair events in individual cancer genomes. Here, we build a statistical framework using a multinomial distribution to assign individual mutations to their cognate mutation signatures. We applied it to 47 million somatic mutations in 1925 publicly available cancer genomes to obtain a mutation signature map at the resolution of individual somatic mutations. Based on mutation signature-level genetic-epigenetic correlative analyses, mutations with transcriptional and replicative strand asymmetries show different enrichment patterns across genomes, and "transcribed" chromatin states and gene boundaries are particularly vulnerable to transcription-coupled repair activities. While causative processes of cancer-driving mutations can be diverse, as shown for converging effects of multiple mutational processes on TP53 mutations, the substantial fraction of recurrently mutated amino acids points to specific mutational processes, e.g., age-related C-to-T transition for KRAS p.G12 mutations. Our investigation of evolutionary trajectories with respect to mutation signatures further revealed that candidate pairs of early- vs. late-operative mutation processes in cancer genomes represent evolutionary dynamics of multiple mutational processes in the shaping of cancer genomes. We also observed that the local mutation clusters of kataegis often include mutations arising from multiple mutational processes, suggestive of a locally synchronous impact of multiple mutational processes on cancer genomes. Taken together, our examination of the genome-wide landscape of mutation signatures at the resolution of individual somatic mutations shows the spatially and temporally distinct mutagenesis-repair-replication histories of various mutational processes and their effects on shaping cancer genomes.
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http://dx.doi.org/10.1038/s12276-022-00808-xDOI Listing
July 2022

First report of leaf spot on DC. caused by in China.

Plant Dis 2022 Jul 28. Epub 2022 Jul 28.

Heilongjiang University of Chinese Medicine, college of Pharmacy, Harbin, Heilongjiang, China;

DC. is distributed in China, Korea, Mongolia, Russia and Japan. This plant is both ornamental and medical, used in the treatment of nervous disease, dyskinesia and other diseases. In September, 2019, a leaf spot on was first found in a 5 ha plantation in Harbin, Heilongjiang Province, China. The incidence was about 80%. The symptoms were elliptical, circular, or irregular brown to black necrotic lesions in leaf apex and leaf margin. Ten fresh sample leaves with typical symptoms were collected from ten plants. The tissues (5mm×5mm) between symptomatic and healthy junction were cut and surface disinfected in 75% ethanol, and with 7% NaClO for 1 min, then rinsed three times with sterilized water, 30s each time. The sterilized tissues were inoculated on potato dextrose agar (PDA) plates for 7 days at 25℃. The colonies were obtained and transferred onto new PDA and potato carrot agar (PCA) plates by single spore method to further purify. After 7 days, the colonies on PDA were 50 to 63 mm in diameter, circular, grayish brown, with white aerial hyphae. A total of 150 conidia on PCA were single or in chains, ovoid, inverted pear, 2 to 7 transverse septa, 0 to 3 longitudinal or oblique septa, 17.5 to 57.5 × 7.5 to 17.5 μm. Beaks and supposititious beaks were mostly columnar, rarely conical, 2.5 to 6.0 × 2.0 to 3.0 μm. Conidiophores were solitary or clustered, pale brown, erect or bent, branched or unbranched, separated, 112.0 to 151.0 × 5.1 to 14.7 μm. Ten isolates purified on PDA were obtained. Morphological identification showed the ten isolates were similar and appeared to be (Simmons, 2007). Two strains from ten isolates were selected for molecular identification. Genomic DNA was extracted from mycelia of two isolates (LD2020520 and LD2020521) on PDA using a modified CTAB method. Internal transcribed spacer rDNA regions (ITS), RNA polymerase II second largest subunit gene (RPB2), Alternaria major allergen (Alt a 1), endopolygalacturonase (endoPG) and glyceraldehyde 3-phosphate dehydrogenase (gpd) were amplified and sequenced using two directional sequencing with the primers ITS1/ITS4, RPB2-F/RPB2-R, Alt-F/Alt-R, end-F/end-R and gpd-F/gpd-R (Woudenberg et al. 2015). The sequences obtained were deposited in GenBank (ITS: MT501762, OK571395; RPB2: MT506027, OK631891; Alt a 1: MT506026, OK631890; endoPG: ON054189, ON054188; gpd: ON054191, ON054190). The phylogenetic analysis of maximum-likelihood tree by MEGA 7 software showed that the two isolates had 99% identity with the CBS 916.96. For pathogenicity testing, eighteen leaves of six 5-week-old plants were sprayed with spore suspensions (1×106 spores /mL) of the 7 days-old isolates LD2020521 and LD2020520 (Each isolate infected three plants and each infected three leaves). Three plants were sprayed with sterile distilled water as a control group. The plants were incubated at 25℃. After 15 days, taupe irregular spots appeared on the leaves. The pathogenicity test was repeated three times. The same fungi were re-isolated from the inoculated leaves and with the same morphological and molecular characteristics as LD2020520 and LD 2020521, fulfilling Koch's postulates. No fungi were isolated from the control group. This is the first report of leaf spot on caused by Leaf spot can reduce the yields of . This study provides a reference for the prevention and treatment to the leaf spot of .
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http://dx.doi.org/10.1094/PDIS-04-22-0902-PDNDOI Listing
July 2022

DOA Estimation in B5G/6G: Trends and Challenges.

Sensors (Basel) 2022 Jul 8;22(14). Epub 2022 Jul 8.

College of Electronic Countermeasure, National University of Defense Technology, Hefei 230037, China.

Direction-of-arrival (DOA) estimation is the preliminary stage of communication, localization, and sensing. Hence, it is a canonical task for next-generation wireless communications, namely beyond 5G (B5G) or 6G communication networks. Both massive multiple-input multiple-output (MIMO) and millimeter wave (mmW) bands are emerging technologies that can be implemented to increase the spectral efficiency of an area, and a number of expectations have been placed on them for future-generation wireless communications. Meanwhile, they also create new challenges for DOA estimation, for instance, through extremely large-scale array data, the coexistence of far-field and near-field sources, mutual coupling effects, and complicated spatial-temporal signal sampling. This article discusses various open issues related to DOA estimation for B5G/6G communication networks. Moreover, some insights on current advances, including arrays, models, sampling, and algorithms, are provided. Finally, directions for future work on the development of DOA estimation are addressed.
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http://dx.doi.org/10.3390/s22145125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318173PMC
July 2022

Fabrication and Electrical Characterization of High Aspect Ratio Through-Silicon Vias with Polyimide Liner for 3D Integration.

Micromachines (Basel) 2022 Jul 20;13(7). Epub 2022 Jul 20.

School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing 100081, China.

High aspect ratio (HAR) through-silicon vias (TSVs) are in urgent need to achieve smaller keep-out zones (KOZs) and higher integration density for the miniaturization of high-performance three-dimensional (3D) integration of integrated circuits (IC), micro-electro-mechanical systems (MEMS), and other devices. In this study, HAR TSVs with a diameter of 11 μm and an aspect ratio of 10:1 are successfully fabricated in a low-cost process flow. Conformal polyimide (PI) liners are deposited using a vacuum-assisted spin coating technique, and the effects of spin coating time and speed on the deposition results are discussed. Then, continuous Cu seed layers are fabricated by sequential sputtering and ultrasound-assisted electroless plating. Additionally, void-free and seamless Cu conductors are formed by electroplating. Moreover, a semi-additive method is used to fabricate the redistribution layers (RDLs) on the insulating layers of photosensitive PI (PSPI). Notably, a plasma bombardment process is introduced to remove residual PSPI in the contact windows between RDLs and central pillars. Results show that the resistance of a single TSV from a daisy chain of 144 TSVs with density of 2000/mm is about 28 mΩ. Additionally, the S-parameters of a single TSV are obtained using L-2L de-embedding technology, and the experimental and simulated results agree well. The proposed low-cost fabrication technologies and the related electrical characterization of PI-TSVs are significant for the application of HAR TSVs in modern heterogeneous integration systems.
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http://dx.doi.org/10.3390/mi13071147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323921PMC
July 2022

Surface Quality Control Strategy of Aspherical Mold Based on Screw Feed Polishing of Small Polishing Tool.

Materials (Basel) 2022 Jul 12;15(14). Epub 2022 Jul 12.

State Key Laboratory of Precision Electronic Manufacturing Technology and Equipment, Guangdong University of Technology, Guangzhou 510006, China.

For small aspherical molds, it is difficult for the existing polishing method to take into account the correction of the surface error and the control of the uniformity of the surface roughness (SR) distribution, because the polishing tool is always larger than the small mold. Therefore, we used viscoelastic polyester fiber cloth to wrap the small steel ball as a polishing tool to adapt to the surface shape change of the aspherical mold, and designed a semi-flexible small polishing disc tool with microstructure, which can better adapt to the curvature change of aspherical surface and obtain better SR Ra. At the same time, a combined polishing method of constant speed and variable speed for screw feed was proposed to improve the uniformity of SR distribution in the paper. Then, a series of theoretical analysis and experimental verification were carried out in this paper to predict the tool influence function (TIF) of the two polishing tools and the effectiveness of the combined polishing method. In the experiment, a TIF bandwidth of about 0.46 mm was obtained with a small spherical polishing tool, which favors the surface shape correction of the small aspherical mold. The experiment of uniform removal with a small polishing disc tool was carried out to quickly reduce the Ra. Finally, the surface quality of the aspherical mold was effectively improved, combined with the constant speed and variable speed polishing modes of screw feed of the small spherical polishing tool and the smoothing effect of the small polishing disc tool. The peak valley (PV) of two small aspherical molds with an optical effective diameter less than 13 mm converged from 0.3572 μm and 0.2075 μm to 0.1282 μm and 0.071 μm, respectively. At the same time, the SR dispersion coefficient was reduced from 27.9% and 41.6% to 14.2% and 12.7%, respectively. The study provides a good solution for the surface quality control of small aspherical molds.
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http://dx.doi.org/10.3390/ma15144848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317048PMC
July 2022

Bone Density May Be a Promising Predictor for Blood Loss during Total Hip Arthroplasty.

J Clin Med 2022 Jul 7;11(14). Epub 2022 Jul 7.

Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Background: Total hip arthroplasty (THA), which is performed mostly in elderly individuals, can result in substantial blood loss and thereby imposes a significant physical burden and risk of blood transfusion. The femoral neck cut and reamed acetabulum are the main sites of intraoperative bleeding. Whether the bone density in that region can be used to predict the amount of blood loss in THA is unknown.

Methods: We retrospectively analyzed adult patients undergoing primary THA in the Department of Orthopedics, Peking Union Medical College Hospital, from January 2018 to January 2020. All these patients underwent primary unilateral THA. Patients had their bone mineral density (BMD) recorded within the week before surgery and were stratified and analyzed for perioperative blood loss. Multivariable regressions were utilized to adjust for differences in demographics and comorbidities among groups.

Results: A total of 176 patients were included in the study. Intraoperative blood loss was 280.1 ± 119.56 mL. Pearson correlation analysis showed a significant correlation between blood loss and preoperative bone density of both the femoral greater trochanter (R = 0.245, = 0.001) and the Ward's triangle (R = 0.181, = 0.016). Stepwise multiple linear regression showed that preoperative bone density of the greater trochanter ( = 0.015, 95% CI: 0.004-0.049) and sex ( = 0.002) were independent risk factors for THA bleeding. The area under the receiver operating characteristic curve (AUROC) of the greater trochanter and Ward's triangle was 0.593 (95% CI: 0.507-0.678, = 0.035) and 0.603 (95% CI: 0.519-0.688, = 0.018), respectively. The cutoff T value on the femoral greater trochanter for predicting higher bleeding was -1.75.

Conclusions: In THA patients, preoperative bone density values of the femoral greater trochanter and sex could be promising independent predictors for bleeding during surgery. Osteoporosis and female patients might have lower blood loss in the THA operation.
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http://dx.doi.org/10.3390/jcm11143951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325145PMC
July 2022

-Mediated Glycosylation Plays an Important Role in Lignin Formation and Stone Cell Development in Pears ().

Int J Mol Sci 2022 Jul 18;23(14). Epub 2022 Jul 18.

School of Life Sciences, Anhui Agricultural University, Hefei 230036, China.

Glycosylation is necessary for many processes of plant secondary metabolism. It can maintain plant homeostasis and is of great significance to normal plant growth and development. At present, the significance of glycosylation for lignin biosynthesis has been proven in some plants, but it has not yet been reported in pears. We used in situ hybridization, in vitro expression, substrate catalysis, transgenic , and transient transformation of pear fruit in our investigation, which was predicated on the identification of a gene that may be involved in lignin monolignol glycosylation according to our previous work. These results revealed that transcripts were localized to some pulp cell walls, lignin deposition, and stone cell areas of pear fruit. The recombinant PbUGT72AJ2-pGEX4T-1 protein had activity against coniferyl alcohol and sinapyl alcohol, and its catalytic efficiency against coniferyl alcohol was higher than that against sinapyl alcohol. When was transferred into mutants, it was found that some characteristics of mutants were restored. In , overexpression of enhanced the contents of coniferin and syringin, whereas lignification did not change significantly. Transient transformation of pear fruit showed that when in pear fruit was silenced by RNA interference, the content of lignin and stone cells in pear fruit increased, whereas the gene was overexpressed in pear fruit, and there was almost no change in the pear fruit compared with the control. Lignin deposition in pear fruit was closely related to stone cell development. In this study, we proved that plays an important role in lignin deposition and stone cell development in pear fruit, which provides a molecular biological basis for improving pear fruit quality at the molecular level.
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http://dx.doi.org/10.3390/ijms23147893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318811PMC
July 2022

Exploring the Chinese Public's Perception of Omicron Variants on Social Media: LDA-Based Topic Modeling and Sentiment Analysis.

Int J Environ Res Public Health 2022 Jul 8;19(14). Epub 2022 Jul 8.

School of Journalism and Communication, Jinan University, Guangzhou 510632, China.

The COVID-19 pandemic caused by SARS-CoV-2 is still raging. Similar to other RNA viruses, SARS-COV-2 is constantly mutating, which leads to the production of many infectious and lethal strains. For instance, the omicron variant detected in November 2021 became the leading strain of infection in many countries around the world and sparked an intense public debate on social media. The aim of this study is to explore the Chinese public's perception of the omicron variants on social media. A total of 121,632 points of data relating to omicron on Sina Weibo from 0:00 27 November 2021 to 23:59:59 30 March 2022 (Beijing time) were collected and analyzed with LDA-based topic modeling and DLUT-Emotion ontology-based sentiment analysis. The results indicate that (1) the public discussion of omicron is based on five topics, including omicron's impact on the economy, the omicron infection situation in other countries/regions, the omicron infection situation in China, omicron and vaccines and pandemic prevention and control for omicron. (2) From the 3 sentiment orientations of 121,632 valid Weibo posts, 49,402 posts were judged as positive emotions, accounting for approximately 40.6%; 47,667 were negative emotions, accounting for nearly 39.2%; and 24,563 were neutral emotions, accounting for about 20.2%. (3) The result of the analysis of the temporal trend of the seven categories of emotion attribution showed that fear kept decreasing, whereas good kept increasing. This study provides more insights into public perceptions of and attitudes toward emerging SARS-CoV-2 variants. The results of this study may provide further recommendations for the Chinese government, public health authorities, and the media to promote knowledge about SARS-CoV-2 variant pandemic-resistant messages.
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http://dx.doi.org/10.3390/ijerph19148377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319145PMC
July 2022

Ultra-Sensitive and Rapid Detection of Pathogenic Based on the CRISPR/Cas12a Nucleic Acid Identification Platform.

Foods 2022 Jul 21;11(14). Epub 2022 Jul 21.

State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.

is a dangerous foodborne human pathogen that mainly causes gastroenteritis. Ideal methods for the detection of pathogens in food should be rapid, sensitive, specific, and cost effective. To this end, novel in vitro nucleic acid identification methods based on clustered, regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) endonuclease have received increasing attention. In this study, a simple, visual, and ultrasensitive method, based on CRISPR/Cas12a with recombinase polymerase amplification (RPA), was developed for the detection of . The results show that a specific attachment invasion locus gene () can be rapidly detected using a CRISPR/Cas12a-RPA-based system. Application of the method to raw pork, which was artificially infected with , achieved an estimated detection limit of 1.7 CFU/mL in less than 45 min, and this was 100 times lower compared with qPCR. The results indicated that the CRISPR/Cas12a-RPA system has good potential for monitoring pathogenic in the chilled meat supply chain.
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http://dx.doi.org/10.3390/foods11142160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318358PMC
July 2022

Cochlear Implantation Outcomes in Patients with Auditory Neuropathy Spectrum Disorder of Genetic and Non-Genetic Etiologies: A Multicenter Study.

Biomedicines 2022 Jun 28;10(7). Epub 2022 Jun 28.

Department of Otolaryngology, National Taiwan University Hospital, Taipei 10002, Taiwan.

With diverse etiologies and clinical features, the management of pediatric auditory neuropathy spectrum disorder (ANSD) is often challenging, and the outcomes of cochlear implants (CIs) are variable. This study aimed to investigate CI outcomes in pediatric patients with ANSD of different etiologies. Thirty-six children with ANSD who underwent cochlear implantation between 2001 and 2021 were included. Comprehensive etiological analyses were conducted, including a history review, next-generation sequencing-based genetic examinations, and imaging studies using high-resolution computed tomography and magnetic resonance imaging. Serial behavioral and speech audiometry were performed before and after surgery, and the outcomes with CI were evaluated using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores. By etiology, 18, 1, 1, and 10 patients had -related, -related, -related, and cochlear nerve deficiency (CND)-related ANSD, respectively. Six patients had no definite etiology. The average CI-aided behavioral threshold was 28.3 ± 7.8 dBHL, and those with CND-related ANSD were significantly worse than -related ANSD. The patients' median CAP and SIR scores were 6 and 4, respectively. Favorable CI outcomes were observed in patients with certain etiologies of ANSD, particularly those with (CAP/SIR scores 5-7/2-5), (CAP/SIR score 6/5), and variants (CAP/SIR score 7/5). Patients with CND had suboptimal CI outcomes (CAP/SIR scores 2-6/1-3). Identifying the etiologies in ANSD patients is crucial before surgery and can aid in predicting prognoses.
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http://dx.doi.org/10.3390/biomedicines10071523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313466PMC
June 2022

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation.

J Transl Med 2022 07 25;20(1):334. Epub 2022 Jul 25.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Effective treatment is needed for advanced, inoperable, or chemotherapy-resistant cervical cancer patients. Immunotherapy has become a new treatment modality for cervical cancer patients, and there is an urgent need to identify additional targets for cervical cancer immunotherapy.

Methods: In this study the core gene, RGS1, which affects immune status and the FIGO stage of cervical cancer patients was identified by WGCNA analysis and differential analysis using TCGA database. 10 related genes interacting with RGS1 were identified using PPI network, and the functional and immune correlations were analyzed. Based on the expression of RGS1 and related genes, the consensus clustering method was used to divide CESC patients into two groups (group 1, high expression of RGS1; group 2, low expression of RGS1). Then, the functional enrichment analysis was used to search for the functional differences in differentially expressed genes (DEGs) between group 1 and group 2. Immune infiltration analysis was performed using ESTIMATE, CIBERSORT, and ssGSEA, and the differences in expression of immune checkpoint inhibitors (ICIs) targets were assessed between the two groups. We investigated the effect of RGS1 on the clinical relevance of CESC patients, and experimentally verified the differences in RGS1 expression between cervical cancer patient tissues and normal cervical tissues, the role of RGS1 in cell function, and the effect on tumor growth in tumor-bearing mice.

Results: We found that RGS1 was associated with CD4, GNAI3, RGS2, GNAO1, GNAI2, RGS20, GNAZ, GNAI1, HLA-DRA and HLA-DRB1, especially CD4 and RGS2. Functional enrichment of DEGs was associated with T cell activation. Compared with group 2, group 1 had stronger immune infiltration and higher ICI target expression. RGS1 had higher expression in cervical cancer tissues than normal tissues, especially in HPV-E6 positive cancer tissues. In cervical cancer cell lines, knockdown of RGS1 can inhibited cell proliferation, migration, invasion, and tumor growth in nude mice and promoted apoptosis.

Conclusions: RGS1, as an oncogenic gene of cervical cancer, affects the immune microenvironment of patients with cervical cancer and may be a target of immunotherapy.
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http://dx.doi.org/10.1186/s12967-022-03526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310486PMC
July 2022

Multi-Label Attribute Selection of Arrhythmia for Electrocardiogram Signals with Fusion Learning.

Bioengineering (Basel) 2022 Jun 22;9(7). Epub 2022 Jun 22.

Department of Computer and Information Science, University of Macau, Taipa 999078, China.

There are three primary challenges in the automatic diagnosis of arrhythmias by electrocardiogram (ECG): the significant variation among individual patients, the multiple pathologies in the ECG signal and the high cost in annotating clinical ECG with the corresponding labels. Traditional ECG processing approaches rely heavily on prior knowledge, such as those from feature extraction and waveform analysis. The preprocessing for prior knowledge incurs computational overhead. Furthermore, standard deep learning methods do not fully consider the dynamic temporal, spatial and multi-labeling characteristics of ECG data. In clinical ECG waveforms, it is common to see multi-labeling in which a patient is labeled with multiple classes of arrhythmias. However, multiclass approaches in current research mainly solve the multi-label machine learning problem, ignoring the correlation between diseases, resulting in information loss. In this paper, an arrhythmia detection and classification scheme called multi-label fusion deep learning is proposed. The objective is to build a unified system with automatic feature learning which supports effective multi-label classification. First, a multi-label ECG-based feature selection method is combined with a matrix decomposition and sparse learning theory. The optimal feature subset is selected as a preprocessing algorithm for ECG data. A multi-label classifier is then constructed by fusing CNN and RNN networks to fully exploit the interactions and features of the time and space dimensions. The experimental result demonstrates that the proposed method can achieve a state-of-the-art performance compared to other algorithms in multi-label database experiments.
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http://dx.doi.org/10.3390/bioengineering9070268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312290PMC
June 2022

Characterization of the Immune Cell Infiltration Landscape in Esophageal Squamous Cell Carcinoma.

Front Oncol 2022 7;12:879326. Epub 2022 Jul 7.

Departments of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Background: Immunotherapy has achieved remarkable efficacy in treating oesophageal squamous cell carcinoma (ESCC). However, this treatment has limited efficacy in some patients. An increasing number of evidence suggested that immune cells within the tumour microenvironment (TME) are strongly related to immunotherapy response and patient prognosis. Thus, the landscape of immune cell infiltration (ICI) in ESCC needs to be mapped.

Methods: In the study, the ICI pattern in 206 cases of ESCC was characterised by two algorithms, namely, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). The ICI score of each specimen was calculated by principal component analysis (PCA) according to ICI signature genes A (ICISGA) and B (ICISGB). The prognostic difference was evaluated by using the Kaplan-Meier method. The related pathways of ICI score were investigated by applying gene set enrichment analysis (GSEA). The R packages of 'regplot', 'timeROC' and 'rms' were applied for the construction of nomogram model.

Result: Three TME subtypes were identified with no prognostic implication. A total of 333 differentially expressed genes (DEGs) among immune subtypes were determined, among which ICISGA and ICISGB were identified. Finally, ICI scores were constructed, and the patients were grouped into high or low ICI score group. Compared with the low ICI score group, the high ICI score group had better prognosis. GSEA revealed that the high ICI score group referred to multiple signalling pathways, including B cell receptor, Fc gamma R-mediated phagocytosis, NOD-like receptor and TGF-β signalling pathways. In addition, the nomogram model was constructed to evaluate 1-, 3- and 5-year probability of death in an ESCC patient. The ROC and calibration curves indicated that the model has a good discrimination ability.

Conclusion: We depicted a comprehensive ICI landscape in ESCC. ICI score may be used as a predictor of survival rate, which may be helpful for guiding immunotherapy in the future.
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http://dx.doi.org/10.3389/fonc.2022.879326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300817PMC
July 2022

[Targeted Drug Therapy for Intracranial Tumors].

Sichuan Da Xue Xue Bao Yi Xue Ban 2022 Jul;53(4):564-572

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Intracranial tumors seriously affect the physical and mental health of humans. Due to variations in the nature and the growth site of tumors, individualized and specific treatment of patients with intracranial tumor has become a hotspot topic of research, and targeted drug therapy of intracranial tumors, an important subspecialty of precision medicine, has become a key issue that scientists are working hard to tackle. At present, the rapid development in molecular biology and genomics has provided corresponding targets for precision therapies of tumors. However, the blood-brain barrier and blood-tumor barrier prevent drugs from reaching intracranial targets. Therefore, finding effective ways to elevate the concentration of intracranial drugs has become the key issue concerning existing targeted therapies for intracranial tumors. Herein, we reviewed the current status of targeted drug therapy for different intracranial tumors and discussed their efficacy, intending to provide new perspectives for the treatment of intracranial tumors with targeted drugs in the future.
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http://dx.doi.org/10.12182/20220760102DOI Listing
July 2022

Acylations in cardiovascular diseases: advances and perspectives.

Chin Med J (Engl) 2022 Jul 21. Epub 2022 Jul 21.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

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http://dx.doi.org/10.1097/CM9.0000000000001941DOI Listing
July 2022

Surveillance of adverse events following immunisation in Australia annual report, 2020.

Commun Dis Intell (2018) 2022 Jul 21;46. Epub 2022 Jul 21.

National Centre for Immunisation Research and Surveillance, The University of Sydney and The Children's Hospital at Westmead, Sydney, Australia.

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2020, reported to the Therapeutic Goods Administration (TGA), and describes reporting trends over the 21-year period from 1 January 2000 to 31 December 2020. There were 3,827 AEFI records for vaccines administered in 2020, an annual AEFI reporting rate of 14.9 per 100,000 population. There was a slight (3.8%) decrease in the overall AEFI reporting rate in 2020 compared with 2019 (15.5 per 100,000 population). This decrease in the AEFI reporting rate in 2020 is potentially due to the impact of coronavirus disease 2019 (COVID-19) and was mainly from a decline in reported adverse events related to HPV, dTpa, and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2020 were similar to 2019. The most commonly reported adverse events were injection site reaction (37.1%); pyrexia (18.1%); rash (15.8%); vomiting (7.6%); pain (7.4%); headache (5.7%); and urticaria (5.1%). There were six deaths reported to the TGA. In one of the reports, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining five reports, no clear causal relationship with vaccination was found.
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http://dx.doi.org/10.33321/cdi.2022.46.47DOI Listing
July 2022

Determining Factors Influencing RAS Inhibitors Re-Initiation in ICU: A Modified Delphi Method.

Can J Kidney Health Dis 2022 15;9:20543581221112266. Epub 2022 Jul 15.

Centre hospitalier de l'Université de Montréal Research Center, QC, Canada.

Background: Renin-angiotensin system inhibitors (RASi) are not re-initiated for almost a quarter of patients who suffered acute kidney injury 6 months after discharge. This discontinuation might be partly explained by the nephrotoxicity of these medications, yet they remain of benefit, especially for patients with heart failure.

Objective: To determine the factors deemed by clinicians to influence RASi re-initiation and set threshold values for important safety parameters.

Design: Three-round modified online Delphi survey.

Setting: The study was conducted in Quebec, Canada.

Participants: Twenty clinicians from nephrology, intensive care medicine, and internal medicine.

Measurements: The factors' importance was rated on 4-point Likert-type scale, ranging from "not important" to "very important" by the panelists.

Methods: We conducted a brief literature review to uncover possible influencing factors followed by a 3-round modified Delphi survey to establish a consensus on the importance of these factors.

Results: We recruited 20 clinicians (7 nephrologists, 3 internists, and 10 intensive care physicians). We created a list of 25 factors, 15 of which met consensus. Eleven of these factors, including serum creatinine, glomerular filtration rate, and acute kidney injury (AKI) stage, were deemed as important while 4, such as responsibility ambiguity and absence of feedback, were deemed as not important. The majority of the 10 factors which did not meet consensus were related to the clinical setting, such as a pharmacist follow-up and the required time to ensure optimal RASi re-initiation.

Limitations: Quebec clinicians' agreement might not reflect the opinion of the rest of Canada. The survey measures clinicians' belief rather than their actual practice.

Conclusion: Renin-angiotensin system inhibitors re-initiation is a rather complex concept which encompasses several factors. Our research uncovered some of these factors which may be used to develop guidelines on optimal RASi re-initiation.
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http://dx.doi.org/10.1177/20543581221112266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290153PMC
July 2022

Primordial Capsid and Spooled ssDNA Genome Structures Unravel Ancestral Events of Eukaryotic Viruses.

mBio 2022 Jul 20:e0015622. Epub 2022 Jul 20.

The Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala Universitygrid.8993.b, Uppsala, Sweden.

Marine algae viruses are important for controlling microorganism communities in the marine ecosystem and played fundamental roles during the early events of viral evolution. Here, we have focused on one major group of marine algae viruses, the single-stranded DNA (ssDNA) viruses from the family. We present the capsid structure of the bacilladnavirus DNA virus type II (CtenDNAV-II), determined at 2.4-Å resolution. A structure-based phylogenetic analysis supported the previous theory that bacilladnaviruses have acquired their capsid protein via horizontal gene transfer from a ssRNA virus. The capsid protein contains the widespread virus jelly-roll fold but has additional unique features; a third β-sheet and a long C-terminal tail. Furthermore, a low-resolution reconstruction of the CtenDNAV-II genome revealed a partially spooled structure, an arrangement previously only described for dsRNA and dsDNA viruses. Together, these results exemplify the importance of genetic recombination for the emergence and evolution of ssDNA viruses and provide important insights into the underlying mechanisms that dictate genome organization. Single-stranded DNA (ssDNA) viruses are an extremely widespread group of viruses that infect diverse hosts from all three domains of life, consequently having great economic, medical, and ecological importance. In particular, bacilladnaviruses are highly abundant in marine sediments and greatly influence the dynamic appearance and disappearance of certain algae species. Despite the importance of ssDNA viruses and the last couple of years' advancements in cryo-electron microscopy, structural information on the genomes of ssDNA viruses remains limited. This paper describes two important achievements: (i) the first atomic structure of a bacilladnavirus capsid, which revealed that the capsid protein gene presumably was acquired from a ssRNA virus in early evolutionary events; and (ii) the structural organization of a ssDNA genome, which retains a spooled arrangement that previously only been observed for double-stranded viruses.
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http://dx.doi.org/10.1128/mbio.00156-22DOI Listing
July 2022

SIRT6 in Vascular Diseases, from Bench to Bedside.

Aging Dis 2022 Jul 11;13(4):1015-1029. Epub 2022 Jul 11.

1Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.

Aging is a key risk factor for angiogenic dysfunction and cardiovascular diseases, including heart failure, hypertension, atherosclerosis, diabetes, and stroke. Members of the NAD-dependent class III histone deacetylase family, sirtuins, are conserved regulators of aging and cardiovascular and cerebrovascular diseases. The sirtuin SIRT6 is predominantly located in the nucleus and shows deacetylase activity for acetylated histone 3 lysine 56 and lysine 9 as well as for some non-histone proteins. Over the past decade, experimental analyses in rodents and non-human primates have demonstrated the critical role of SIRT6 in extending lifespan. Recent studies highlighted the pleiotropic protective actions of SIRT6 in angiogenesis and cardiovascular diseases, including atherosclerosis, hypertension, heart failure, and stroke. Mechanistically, SIRT6 participates in vascular diseases epigenetic regulation of endothelial cells, vascular smooth muscle cells, and immune cells. Importantly, SIRT6 activators (e.g., MDL-800/MDL-811) have provided therapeutic value for treating age-related vascular disorders. Here, we summarized the roles of sirtuins in cardiovascular diseases; reviewed recent advances in the understanding of SIRT6 in vascular biology, cardiovascular aging, and diseases; highlighted its therapeutic potential; and discussed future perspectives.
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http://dx.doi.org/10.14336/AD.2021.1204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286919PMC
July 2022

Low-defect-density WS by hydroxide vapor phase deposition.

Nat Commun 2022 Jul 18;13(1):4149. Epub 2022 Jul 18.

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, China.

Two-dimensional (2D) semiconducting monolayers such as transition metal dichalcogenides (TMDs) are promising channel materials to extend Moore's Law in advanced electronics. Synthetic TMD layers from chemical vapor deposition (CVD) are scalable for fabrication but notorious for their high defect densities. Therefore, innovative endeavors on growth reaction to enhance their quality are urgently needed. Here, we report that the hydroxide W species, an extremely pure vapor phase metal precursor form, is very efficient for sulfurization, leading to about one order of magnitude lower defect density compared to those from conventional CVD methods. The field-effect transistor (FET) devices based on the proposed growth reach a peak electron mobility ~200 cm/Vs (~800 cm/Vs) at room temperature (15 K), comparable to those from exfoliated flakes. The FET device with a channel length of 100 nm displays a high on-state current of ~400 µA/µm, encouraging the industrialization of 2D materials.
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http://dx.doi.org/10.1038/s41467-022-31886-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293887PMC
July 2022
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