Annotation of cell types (ACT): a convenient web server for cell type annotation.

BACKGROUND: The advancement of single-cell sequencing has progressed our ability to solve biological questions. Cell type annotation is of vital importance to this process, allowing for the analysis and interpretation of enormous single-cell datasets. At present, however, manual cell annotation which is the predominant approach remains limited by both speed and the requirement of expert knowledge. METHODS: To address these challenges, we constructed a hierarchically organized marker map through manually curating over 26,000 cell marker entries from about 7000 publications. We then developed WISE, a weighted and integrated gene set enrichment method, to integrate the prevalence of canonical markers and ordered differentially expressed genes of specific cell types in the marker map. Benchmarking analysis suggested that our method outperformed state-of-the-art methods. RESULTS: By integrating the marker map and WISE, we developed a user-friendly and convenient web server, ACT ( http://xteam.xbio.top/ACT/ or http://biocc.hrbmu.edu.cn/ACT/ ), which only takes a simple list of upregulated genes as input and provides interactive hierarchy maps, together with well-designed charts and statistical information, to accelerate the assignment of cell identities and made the results comparable to expert manual annotation. Besides, a pan-tissue marker map was constructed to assist in cell assignments in less-studied tissues. Applying ACT to three case studies showed that all cell clusters were quickly and accurately annotated, and multi-level and more refined cell types were identified. CONCLUSIONS: We developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification.

Fe and Cu Double-Doped Co3O4 Nanorod with Abundant Oxygen Vacancies: A High-Rate Electrocatalyst for Tandem Electroreduction of Nitrate to Ammonia.

The electrochemical nitrate reduction reaction (NO3RR) is an attractive green alternative to the conventional Haber-Bosch method for the synthesis of NH3. However, this reaction is a tandem process that involves multiple steps of electrons and protons, posing a significant challenge to the efficient synthesis of NH3. Herein, we report a high-rate NO3RR electrocatalyst of Fe and Cu double-doped Co3O4 nanorod (Fe1/Cu2-Co3O4) with abundant oxygen vacancies, where the Cu preferentially catalyzes the rapid conversion of NO3- to NO2- and the oxygen vacancy in the Co3O4 substrate can accelerate NO2- reduction to NH3. In addition, the introduction of Fe can efficiently capture atomic H* that promotes the dynamics of NO2- to NH3, improving Faradaic efficiency of the produced NH3. Controlled experimental results show that the optimal electrocatalyst of Fe1/Cu2-Co3O4 exhibits good performance with high conversion (93.39%), Faradaic efficiency (98.15%), and ammonia selectivity (98.19%), which is significantly better than other Co-based materials. This work provides guidance for the rational design of high-performance NO3RR catalysts.

Computational Quantification of Cancer Immunoediting.

The remarkable success of cancer immunotherapy has revolutionized cancer treatment, emphasizing the importance of tumor-immune interactions in cancer evolution and treatment. Cancer immunoediting describes the dual effect of tumor-immune interactions: inhibiting tumor growth by destroying tumor cells and facilitating tumor escape by shaping tumor immunogenicity. To better understand tumor-immune interactions, it is critical to develop computational methods to measure the extent of cancer immunoediting. In this review, we provide a comprehensive overview of the computational methods for quantifying cancer immunoediting. We focus on describing the basic ideas, computational processes, advantages, limitations, and influential factors. We also summarize recent advances in quantifying cancer immunoediting studies and highlight future research directions. As the methods for quantifying cancer immunoediting are continuously improved, future research will further help define the role of immunity in tumorigenesis and hopefully provide a basis for the design of new personalized cancer immunotherapy strategies.

The role of closed-loop management of fever patients in a county-level medical community for the prevention and control of the post-coronavirus disease 2019 pandemic.

We built a closed-loop management model for patients with fever in a county-level medical community and explored the role of this model in post-coronavirus disease 2019 (COVID-19) epidemic prevention and control. The subjects included 83,791 patients with fever treated in designated hospitals between February 2020 and April 2021. A pre-hospital, in-hospital, and post-hospital management system for patients with fever in the county-level medical community was established to allow the closed-loop management of these patients. SPSS software (version 13.0) was used to analyze the methods of visiting the hospital, nucleic acid detection in the hospital, and location of the patients after the hospital visit. Chi-square tests were used to compare the methods of visiting and location after hospital visits between patients with and without an epidemiological history. The number of patients with fever in the fever clinic showed a logarithm change (R2 = 0.4710), accompanied by seasonal changes. The number of fever patients with an epidemiological history decreased logarithmically monthly (R2 = 0.8876). Among patients with fever, 99.64% sought medical treatment on their own, with relatively low proportions undergoing home quarantine and requiring centralized quarantine special vehicles. After visiting the fever clinics, 98.56% of patients isolated at home or were monitored, with small proportions of patients requiring hospital admission or centralized isolation. However, the proportions of patients with home and centralized isolation with epidemiology were relatively high, accounting for 20.55% and 27.40% of cases, respectively. Compared to the overall population of patients with fever, the difference was statistically significant (χ2 = 48.881, P = .000). The establishment of a closed-loop management model for patients with fever in a county-level medical community strengthened the management of these patients. No local cases occurred in Beilun District between March 2020 and April 2021. In the post-COVID-19 era, all medical institutions in the county-level medical community strengthened infectious disease pre-examination and triage and promoted the formation of a strategic pattern of initial diagnosis at the grassroots level, 2-way referral, upper and lower linkage, and joint epidemic prevention. This management was more conducive to COVID prevention and control by hierarchical management according to the presence or absence of an epidemiological history.

BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy.

The mammary gland undergoes fast cell proliferation during early pregnancy, yet the mechanism to ensure genome integrity during this highly proliferative stage is largely unknown. We show that pregnancy triggers replicative stresses leading to genetic instability in mice carrying a mammary specific disruption of breast cancer associated gene-1 (BRCA1). The fast cell proliferation was correlated with enhanced expression of most genes encoding replisomes, which are positively regulated by estrogen/ERα signaling but negatively regulated by BRCA1. Our further analysis revealed two parallel signaling pathways, which are mediated by ATR-CHK1 and WEE1-MCM2 and are responsible for regulating DNA replication checkpoint. Upon DNA damage, BRCA1 deficiency markedly enhances DNA replication initiation and preferably impairs DNA replication checkpoint mediated by ATR and CHK1. Meanwhile, DNA damage also activates WEE1-MCM2 signaling, which inhibits DNA replication initiation and enables BRCA1-deficient cells to avoid further genomic instability. Finally, we demonstrated that overriding this defense by WEE1 inhibition in combination with cisplatin, which causes DNA damage, serves as a promising therapeutic approach for killing BRCA1-deficient cancer cells.

Ultrasmall MnO Nanoparticles Supported on Nitrogen-Doped Carbon Nanotubes as Efficient Anode Materials for Sodium Ion Batteries.

Sodium ion batteries (SIBs) have attracted increasing attentions as promising alternatives to lithium ion batteries (LIBs). Herein, we design and synthesize ultrasmall MnO nanoparticles (∼4 nm) supported on nitrogen-doped carbon nanotubes (NDCT@MnO) as promising anode materials of SIBs. It is revealed that the carbonization temperature can greatly influence the structural features and thus the Na-storage behavior of the NDCT@MnO nanocomposites. The synergetic interaction between MnO and NDCT in the NDCT@MnO nanocomposites provides high rate capability and long-term cycling life due to high surface area, electrical conductivity, enhanced diffusion rate of Na+ ions, and prevented agglomeration and high stability of MnO nanoparticles. The resulting SIBs provide a high reversible specific capacity of 709 mAh g-1 at a current density of 0.1 A g-1 and a high capacity of 536 mAh g-1 almost without loss after 250 cycles at 0.2 A g-1. Even at a high current density of 5 A g-1, a capacity of 273 mAh g-1 can be maintained after 3000 cycles.

Nitrogen Doped Macroporous Carbon as Electrode Materials for High Capacity of Supercapacitor.

Nitrogen doped carbon materials as electrodes of supercapacitors have attracted abundant attention. Herein, we demonstrated a method to synthesize N-doped macroporous carbon materials (NMC) with continuous channels and large size pores carbonized from polyaniline using multiporous silica beads as sacrificial templates to act as electrode materials in supercapacitors. By the nice carbonized process, i.e., pre-carbonization at 400 °C and then pyrolysis at 700/800/900/1000 °C, NMC replicas with high BET specific surface areas exhibit excellent stability and recyclability as well as superb capacitance behavior (~413 F ⋅ g-1) in alkaline electrolyte. This research may provide a method to synthesize macroporous materials with continuous channels and hierarchical pores to enhance the infiltration and mass transfer not only used as electrode, but also as catalyst somewhere micro- or mesopores do not work well.

Bifunctional Nitrogen-Doped Microporous Carbon Microspheres Derived from Poly(o-methylaniline) for Oxygen Reduction and Supercapacitors.

Heteroatom-doped carbon materials have attracted significant attention because of their applications in oxygen reduction reaction (ORR) and supercapacitors. Here we demonstrate a facile poly(o-methylaniline)-derived fabrication of bifunctional microporous nitrogen-doped carbon microspheres (NCMSs) with high electrocatalytic activity and stability for ORR and energy storage in supercapacitors. At a pyrolysis temperature of 900 °C, the highly dispersed NCMSs present a high surface area (727.1 m(2) g(-1)), proper total content of doping N, and high concentration of quaternary N, which exhibit superior electrocatalytic activities for ORR to the commercial Pt/C catalysts, high specific capacitance (414 F g(-1)), and excellent durability, making them very promising for advanced energy conversion and storage. The presented conducting polymer-derived strategy may provide a new way for the fabrication of heteroatom-doped carbon materials for energy device applications.

Heteroatom-Doped Carbon Nanostructures Derived from Conjugated Polymers for Energy Applications.

Heteroatom-doped carbon materials have been one of the most remarkable families of materials with promising applications in fuel cells, supercapacitors, and batteries. Among them, conjugated polymer (CP)-derived heteroatom-doped carbon materials exhibit remarkable electrochemical performances because the heteroatoms can be preserved at a relatively high content and keep stable under harsh working conditions. In this review, we summarized recent advances in the rational design and various applications of CP-derived heteroatom-doped carbon materials, including polyaniline (PANI), polypyrrole (PPy), and their ramification-derived carbons, as well as transition metal-carbon nanocomposites. The key point of considering CP-derived heteroatom-doped carbon materials as important candidates of electrode materials is that CPs contain only nonmetallic elements and some key heteroatoms in their backbones which provide great chances for the synthesis of metal-free heteroatom-doped carbon nanostructures. The presented examples in this review will provide new insights in designing and optimizing heteroatom-doped carbon materials for the development of anode and cathode materials for electrochemical device applications.

TaPP2C1, a Group F2 Protein Phosphatase 2C Gene, Confers Resistance to Salt Stress in Transgenic Tobacco.

Group A protein phosphatases 2Cs (PP2Cs) are essential components of abscisic acid (ABA) signaling in Arabidopsis; however, the function of group F2 subfamily PP2Cs is currently less known. In this study, TaPP2C1 which belongs to group F2 was isolated and characterized from wheat. Expression of the TaPP2C1-GFP fusion protein suggested its ubiquitous localization within a cell. TaPP2C1 expression was downregulated by abscisic acid (ABA) and NaCl treatments, but upregulated by H2O2 treatment. Overexpression of TaPP2C1 in tobacco resulted in reduced ABA sensitivity and increased salt resistance of transgenic seedlings. Additionally, physiological analyses showed that improved resistance to salt stress conferred by TaPP2C1 is due to the reduced reactive oxygen species (ROS) accumulation, the improved antioxidant system, and the increased transcription of genes in the ABA-independent pathway. Finally, transgenic tobacco showed increased resistance to oxidative stress by maintaining a more effective antioxidant system. Taken together, these results demonstrated that TaPP2C1 negatively regulates ABA signaling, but positively regulates salt resistance. TaPP2C1 confers salt resistance through activating the antioxidant system and ABA-independent gene transcription process.

Ectopic expression of wheat TaCIPK14, encoding a calcineurin B-like protein-interacting protein kinase, confers salinity and cold tolerance in tobacco.

Calcineurin B-like protein-interacting protein kinases (CIPKs) are components of Ca(2+) signaling in responses to abiotic stresses. In this work, the full-length cDNA of a novel CIPK gene (TaCIPK14) was isolated from wheat and was found to have significant sequence similarity to OsCIPK14/15. Subcellular localization assay revealed the presence of TaCIPK14 throughout the cell. qRT-PCR analysis showed that TaCIPK14 was upregulated under cold conditions or when treated with salt, PEG or exogenous stresses related signaling molecules including ABA, ethylene and H2 O2 . Transgenic tobaccos overexpressing TaCIPK14 exhibited higher contents of chlorophyll and sugar, higher catalase activity, while decreased amounts of H2 O2 and malondialdehyde, and lesser ion leakage under cold and salt stresses. In addition, overexpression also increased seed germination rate, root elongation and decreased Na(+) content in the transgenic lines under salt stress. Higher expression of stress-related genes was observed in lines overexpressing TaCIPK14 compared to controls under stress conditions. In summary, these results suggested that TaCIPK14 is an abiotic stress-responsive gene in plants.

Overexpression of the wheat aquaporin gene, TaAQP7, enhances drought tolerance in transgenic tobacco.

Aquaporin (AQP) proteins have been shown to transport water and other small molecules through biological membranes, which is crucial for plants to combat stress caused by drought. However, the precise role of AQPs in drought stress response is not completely understood in plants. In this study, a PIP2 subgroup gene AQP, designated as TaAQP7, was cloned and characterized from wheat. Expression of TaAQP7-GFP fusion protein revealed its localization in the plasma membrane. TaAQP7 exhibited high water channel activity in Xenopus laevis oocytes and TaAQP7 transcript was induced by dehydration, and treatments with polyethylene glycol (PEG), abscisic acid (ABA) and H(2)O(2). Further, TaAQP7 was upregulated after PEG treatment and was blocked by inhibitors of ABA biosynthesis, implying that ABA signaling was involved in the upregulation of TaAQP7 after PEG treatment. Overexpression of TaAQP7 increased drought tolerance in tobacco. The transgenic tobacco lines had lower levels of malondialdehyde (MDA) and H(2)O(2), and less ion leakage (IL), but higher relative water content (RWC) and superoxide dismutase (SOD) and catalase (CAT) activities when compared with the wild type (WT) under drought stress. Taken together, our results show that TaAQP7 confers drought stress tolerance in transgenic tobacco by increasing the ability to retain water, reduce ROS accumulation and membrane damage, and enhance the activities of antioxidants.

HCV NS5B polymerase inhibitors 1: Synthesis and in vitro activity of 2-(1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives.

2-(1,1-Dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives as potential anti-HCV drugs targeting NS5B polymerase have been investigated. Their synthesis, HCV NS5B polymerase inhibition and replicon activity are discussed.

Rational design based on bioactive conformation analysis of pyrimidinylbenzoates as acetohydroxyacid synthase inhibitors by integrating molecular docking, CoMFA, CoMSIA, and DFT calculations.

Pyrimidinylthiobenzoates constitute an important kind of herbicides targeting acetohydroxyacid synthase (AHAS, EC 2.2.1.6), which catalyze the first common step in branched-chain amino acid biosynthesis. Due to the symmetry of 4,6-dimethoxypyrimidyl, there are two kinds of conformation of pyrimidinylthiobenzoates: one's phenyl is left-extending (named conformation-L); the other's phenyl is right-extending (named conformation-R). On the basis of the assumption that 3D quantitative structure-activity relationship (QSAR) models derived from the bioactive conformation should give the best result, a strategy of density-functional-theory-based 3D-QSAR was proposed to identify the bioactive conformation of pyrimidinylthiobenzoates by integrating the techniques of molecular docking, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and density functional theory calculation. The combination of three criteria of q2, r2, and r2pred obtained from CoMFA and CoMSIA analyses clearly indicated that conformation-R rather than conformation-L might be the bioactive conformation for pyrimidinylthiobenzoates. A further comparison between the two binding modes indicated that pyrimidinylthiobenzoates and sulfonylureas have very similar binding sites, such as Trp586, Arg380, and Pro192. However, Lys251 formed H bonds with sulfonylureas rather than pyrimidinylthiobenzoates. In addition, the orientation of phenyl groups of the two classes of compounds in the binding pocket were revealed to be opposite, which explained why the mutation of Pro192 displayed different sensitivity to sulfonylureas and pyrimidinylthiobenzoates. On the basis of the understanding of interactions between pyrimidinyl-thiobenzoates and AHAS, we designed and synthesized six 8-(4,6-dimethoxypyrimidin-2-yloxy)-4-methylphthalazin-1-one derivatives according to the 3D-QSAR models. The excellent correlation between the tested Ki values against wild-type A. thaliana acetohydroxyacid synthase and the predicted IC50 values demonstrated the high reliability of the established 3D-QSAR models. To our knowledge, this is the first report highlighting the binding mode of herbicidal pyrimidinylthiobenzoates, which consisted of the reported results of herbicide resistance.

Design and syntheses of novel phthalazin-1(2H)-one derivatives as acetohydroxyacid synthase inhibitors.

A series of 2-substituted-8-(4,6-dimethoxypyrimidin-2-yloxy)-4-methylphthalazin-1-one derivatives, 7a-7w, were designed via an ortho-substituent cyclization strategy to discover a new herbicidal lead structure. These compounds were synthesized by a seven-step route using 3-hydroxy-acetophenone as a starting material. Determination of the Ki values against wild-type A. thaliana acetohydroxyacid synthase (AHAS) (EC 4.1.3.18) indicated that some of the compounds displayed good enzyme inhibition activity comparable to that of KIH-6127. The further preliminary bioassay data on weeds showed that the synthesized compounds exhibited typical injury symptoms of AHAS-inhibiting herbicides, and some of them showed broad-spectrum and high herbicidal activities in postemergence treatments against Echinochloa crusgalli, Digitaria sanguinalis, Setaria viridis, Brassica juncea, Amaranthus retroflexus, and Chenopodium album at an application rate of 150 g ai/ha. To our knowledge, this is the first report of methylphthalazin-1-one derivatives as AHAS inhibitors.

[A study on axis length measurement of high myopia with cataract].

PURPOSE: To study the accuracy of axis length measurement on high myopia with cataract. METHODS: A/B scan ultrasonography and IOL-master were used to measure the ocular axial length in 168 high myopic eyes with cataract of 103 cases. B-scan ultrasonography was used to examine posterior scleral staphyloma. Refractive results were recorded during the follow-up after operation to evaluate the accuracy of measurement. RESULTS: The rate of posterior scleral staphyloma was 76.19%. The average postoperative error of refractive of all eyes was between -1.0 D and +1.0 D. CONCLUSION: Accurate data of axis length can be obtained by combining results of A-scan, B-scan ultrasonography and IOL-master for high myopia with cataract, especially for patients with posterior scleral staphyloma.