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A combined process of coagulation pretreatment and three-stage membrane aeration biofilm reactor (MABR) system was successfully applied for the first time to treat actual municipal solid waste leachate (MSWL), which was characterized by high concentrations of toxic hard-to-degrade organics and salinity. The results showed that 9.8%-21.3% of organics could be removed from actual MSWL by coagulation with polymeric aluminum chloride (PAC). Three-stage MABR contributed 95.6% of the chemical oxygen demand (COD) removal, with the influent COD concentration ranging from 6000 to 7000 mg/L. At the same time, the removal efficiencies of total nitrogen (TN) and ammonia (NH 4 + -N) could reach to 84.3% and 79.9% without the addition of external carbon source, respectively. The nitrifying/denitrifying bacteria were enriched in the biofilm including Thiobacillus, Azoarcus and Methyloversatilis, which supported the MABR with high nitrogen removal efficiency and significantly toxic tolerance. Principal component analysis (PCA) and the Pearson correlation coefficients (r) illustrated that aeration pressure is a crucial operational parameter, exhibiting a strong correlation between the MABR performance and microbial communities. This work demonstrates that MABR is an effective and low-energy option for simultaneous removal of carbon and nitrogen in the treatment of MSWL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this work was to develop an anti-CAT-SYI immunoglobulin Y (IgY) antibody that targeted both GtfB (glucosyltransferase B) and GbpB (glucan-binding protein B) and test its anticaries properties in rats., Methods: A new CAT-SYI fusion gene was created utilising functional DNA fragments from the GtfB and GbpB genes. The recombinant antigens, comprising the fused CAT-SYI antigen, GtfB, and GbpB, were expressed and purified using a prokaryotic expression and purification system. The purified recombinant antigens were utilised to immunise laying hens against particular IgY production. The biological activities of these particular IgY antibodies were then assessed both in vitro and in vivo, including their capacity to suppress biofilm formation and tooth caries., Results: Results indicated that these produced IgY antibodies demonstrated a high antibody titer (>0.1 μg/mL) and could precisely recognise and bind to their respective antigens. Furthermore, it was discovered that these specific IgY antibodies successfully bind to Streptococcus mutans and significantly reduce biofilm development. After 8 weeks of ingesting antigen-specific IgY meals, comprising anti-GtfB IgY and anti-GbpB IgY, the severity of dental caries was dramatically reduced in S mutans-infected Sprague-Dawley rats (P < .01). Anti-CAT-SYI IgY therapy significantly reduced tooth cavities by 89.0% in vivo (P < .05) compared to other treatment groups., Conclusions: The anti-CAT-SYI IgY, a multitarget antibody that targets both GtfB and GbpB, displayed excellent inhibitory effects against S mutans, making it a promising targeted method with improved anticaries efficacy and significant application opportunities., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the relative benefits of various non-pharmacological interventions on treating primary dysmenorrhoea within a network meta-analysis., Study Design: Systematic review and Bayesian network meta-analysis., Inclusion Criteria: Randomised controlled trial involving patient with primary dysmenorrhoea and received non-pharmacological interventions., Data Sources: Four databases (Medline, Embase, Cochrane Library and Web of Science) were searched from inception to October first, 2022., Risk-Of-Bias Rob Assessment: RoB 2.0 assessment tools was used to assess the risk of bias in the included studies., Synthesis of Results: Conventional meta-analysis was conducted by pairwise comparison between non-pharmacological therapy and control treatment. The Bayesian network meta-analysis was conducted by the Aggregate Data Drug Information System Software based on the consistency or inconsistency model, and rank probability was used to indicate the priority of non-pharmacological therapy., Results: 33 studies involving eight non-pharmacological interventions were included. With regard to conventional meta-analysis, we selected Visual Analogue Scale (VAS) as primary outcome to evaluate the pain intensity. The result showed that eight interventions (Exercise, Herb, Acupuncture, Aromatherapy, Transcutaneous Electrical Nerve Stimulation, Topical heat, Acupressure, Yoga) displayed positive effect on reduction of menstrual pain compared with placebo or no treatment. A Bayesian network meta-analysis revealed that exercise -3.20 (95% CI -4.01 to -2.34), acupuncture -2.90 (95% CI -3.97 to -2.85) and topical heat -2.97 (95% CI -4.66 to -1.29) probably resulted in a reduction in pain intensity (VAS) ., Conclusions: Non-pharmacological interventions may result in a reduction or slight reduction in pain intensity compared with no treatment or placebo. Specifically, exercise and acupuncture are considered as potentially effective non-pharmacological treatments in short-term treatment. Indeed, larger and better methodological quality research is needed., Trial Registration Number: CRD42022351021., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Monomethyl auristatin F (MMAF), a synthetic analogue of the natural compound dolastatin 10, has garnered significant attention in cancer research due to its high potency in vitro. While previous studies have focused on modifying the N-terminal extension of the amino group and the C-terminal modification of the carboxyl group, there has been limited exploration into modifying the P1 and P5 side chains. In this study, we substituted the valine residue at the P1 position with various natural or unnatural amino acids and introduced triazole functional groups at the P5 side chain. Compounds 11k and 18d exhibited excellent inhibition on tubulin. Additionally, compound 18d demonstrated enhanced cytotoxicity against HCT116 cells compared to the parent compound MMAF, suggesting its potential as a cytotoxic payload for further antibody-drug conjugates (ADCs) development., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The training and inference of Graph Neural Networks (GNNs) are costly when scaling up to large-scale graphs. Graph Lottery Ticket (GLT) has presented the first attempt to accelerate GNN inference on large-scale graphs by jointly pruning the graph structure and the model weights. Though promising, GLT encounters robustness and generalization issues when deployed in real-world scenarios, which are also long-standing and critical problems in deep learning ideology. In real-world scenarios, the distribution of unseen test data is typically diverse. We attribute the failures on out-of-distribution (OOD) data to the incapability of discerning causal patterns, which remain stable amidst distribution shifts. In traditional spase graph learning, the model performance deteriorates dramatically as the graph/network sparsity exceeds a certain high level. Worse still, the pruned GNNs are hard to generalize to unseen graph data due to limited training set at hand. To tackle these issues, we propose the Resilient Graph Lottery Ticket (RGLT) to find more robust and generalizable GLT in GNNs. Concretely, we reactivate a fraction of weights/edges by instantaneous gradient information at each pruning point. After sufficient pruning, we conduct environmental interventions to extrapolate potential test distribution. Finally, we perform last several rounds of model averages to further improve generalization. We provide multiple examples and theoretical analyses that underpin the universality and reliability of our proposal. Further, RGLT has been experimentally verified across various independent identically distributed (IID) and out-of-distribution (OOD) graph benchmarks.

Background: Electrochromic materials can dynamically change their optical properties (such as transmittance, absorbance, and reflectance under the action of an applied voltage, and their research and application in the visible band have been widely concerned. In recent years, with the continuous development of electrochromic technology, the related research has been gradually extended to the infrared region., Objective: This invited review aims to provide an overview of the current status of several inorganic infrared electrochromic materials, to provide some references for future research, and to promote the research and application of electrochromic technology in the infrared region., Methods: This review summarizes various research results in the field of infrared electrochromic, which includes a detailed literature review and patent search. Starting from the key performance parameters and device structure characteristics of infrared electrochromic devices (ECDs), the research and progress of several types of inorganic infrared electrochromic materials, including metal oxides, plasma nanocrystals, and carbon nanomaterials, are mainly presented, and feasible optimization directions are also discussed., Conclusion: We believe that the potential of these materials for civilian and military applications, for example, infrared electrochromic smart windows, infrared stealth/disguise, and thermal control of spacecraft, can be fully exploited by optimizing the materials and their devices to improve their performance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this report, an ammonium metatungstate (AMT) and ferrous chloride [Fe(II)Cl 2 ] electrochromic liquid (ECL) was synthesized using a hydrothermal method, with D 2 O used as the solvent instead of H 2 O. The results show that the use of D 2 O can improve the stability and performance of ECLs. The hydrogen evolution process in electrochromic devices (ECDs) filled with ECL becomes more difficult, while the material exchange process becomes easier. The ECD exhibits a color modulation amplitude of 58%@680 nm at 2 V. After 500 cycles, the device's performance remains above 95% at a current density of 1.5 mA/cm 2 . Hydrogen bonds in D 2 O solutions are expected to exhibit stronger forces compared to those in regular H 2 O solutions. Therefore, we hypothesize that enhancing the strength of hydrogen bonds in H 2 O solutions is an effective approach for improving the performance and stability of electrochromic solutions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross-clade pan-sarbecovirus neutralizing antibodies in survivors of the infection by SARS-CoV-1, the neutralization activity and Fc-mediated effector functions of these cross-reactive antibodies elicited in SARS-CoV-1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc-mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS-CoV-1 convalescents and healthy individuals. Potent cross-clade broadly neutralizing antibodies were observed in SARS-CoV-1 survivors who received a three-dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS-CoV-1 infection may exacerbate the impairment of neutralization activity and Fc-mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Canine coronavirus-human pneumonia-2018 (CCoV-HuPn-2018) was recently isolated from a child with pneumonia. This novel human pathogen resulted from cross-species transmission of a canine coronavirus. It has been known that CCoV-HuPn-2018 uses aminopeptidase N (APN) from canines, felines, and porcines, but not humans, as functional receptors for cell entry. The molecular mechanism of cell entry in CCoV-HuPn-2018 remains poorly understood. In this study, we demonstrated that among the nine APN orthologs tested, the APN of the Mexican free-tailed bat could also efficiently support CCoV-HuPn-2018 spike (S) protein-mediated entry, raising the possibility that bats may also be an alternative host epidemiologically important for the transmission of this virus. The glycosylation at residue N747 of canine APN is critical for its receptor activity. The gain of glycosylation at the corresponding residues in human and rabbit APNs converted them to functional receptors for CCoV-HuPn-2018. Interestingly, the CCoV-HuPn-2018 spike protein pseudotyped virus infected multiple human cancer cell lines in a human APN-independent manner, whereas sialic acid appeared to facilitate the entry of the pseudotyped virus into human cancer cells. Moreover, while host cell surface proteases trypsin and TMPRSS2 did not promote the entry of CCoV-HuPn-2018, endosomal proteases cathepsin L and B are required for the entry of CCoV-HuPn-2018 in a pH-dependent manner. IFITMs and LY6E are host restriction factors for the CCoV-HuPn-2018 entry. Our results thus suggest that CCoV-HuPn-2018 has not yet evolved to be an efficient human pathogen. Collectively, this study helps us understand the cell tropism, receptor usage, cross-species transmission, natural reservoir, and pathogenesis of this potential human coronavirus. IMPORTANCE Viral entry is driven by the interaction between the viral spike protein and its specific cellular receptor, which determines cell tropism and host range and is the major constraint to interspecies transmission of coronaviruses. Aminopeptidase N (APN; also called CD13) is a cellular receptor for HCoV-229E, the newly discovered canine coronavirus-human pneumonia-2018 (CCoV-HuPn-2018), and many other animal alphacoronaviruses. We examined the receptor activity of nine APN orthologs and found that CCoV-HuPn-2018 utilizes APN from a broad range of animal species, including bats but not humans, to enter host cells. To our surprise, we found that CCoV-HuPn-2018 spike protein pseudotyped viral particles successfully infected multiple human hepatoma-derived cell lines and a lung cancer cell line, which is independent of the expression of human APN. Our findings thus provide mechanistic insight into the natural hosts and interspecies transmission of CCoV-HuPn-2018-like coronaviruses., Competing Interests: The authors declare no conflict of interest.

Electron backscatter diffraction (EBSD) can be employed to determine crystal structures but has not been used alone to identify defects at the atom scale due to the lack of understanding of the EBSD patterns generated by various structure defects. In the present work, the EBSD patterns of FCC-Fe with 9-layer, 6-layer and 3-layer twin structures are simulated, respectively, using the revised real space (RRS) method and compared with the counterpart of perfect crystals. Our results show that when the electron beam is incident along a direction parallel to the twin plane, the pattern appears symmetrical with respect to the corresponding Kikuchi band of the twin plane, and the diffraction details within the Kikuchi band also exhibit symmetry with respect to the middle line of the Kikuchi band. Moreover, the overall clarity of the patterns decreases, and the pattern becomes more blurred with increasing the distance from the Kikuchi band corresponding to the twin plane. By contrast, the incident electron beam along the direction perpendicular to the twin plane results in diffraction superposition of the matrix region and the shear region, which shows twofold rotational symmetry with respect to the Kikuchi pole corresponding to the normal to the twin plane. In addition, some extra Kikuchi bands appear in the EBSD patterns due to the long-period structures of the multilayer twins. As the number of multilayer twins decreases, the number of extra Kikuchi bands decreases and the area of the blurring pattern increases. The correlation between twin structures and EBSD patterns provides theoretical insights for identifying twin structures by the EBSD technique., (© 2023 Royal Microscopical Society.)

To study the evolution of stress on the ring and segment interfaces during the construction process of the concrete encapsulation of the main arch ring in a rigid-frame arch bridge, alongside its impact on the ultimate load-bearing capacity of the main arch ring, a 1:10 scale model experiment was conducted by taking the 600 m Tian'e Longtan Bridge as the prototype. The key cross-section concrete strain data were collected during the entire construction process of the main arch ring via fiber-optic strain sensors, which were used to investigate the stress evolution at ring and segment interfaces. ANSYS APDL was employed to simulate the ultimate bearing capacity under various loading conditions of two different finite element models, which were, respectively, formed segmentally and by single pouring. The results revealed that (1) after the closure of the concrete encapsulation of the main arch ring, the concrete stress in the cross-section exhibits significant stress disparities. At the same cross-section, the level of the web concrete stress can reach 76% of the floor concrete stress, while the roof concrete stress level is less than 20% of the floor concrete stress. (2) At the junction of two adjacent work planes, there are considerable differences in the stress levels of the concrete on both sides. After the closure of the main arch ring, the intersegment stress ratios of the floor, web, and roof concrete are 60~70%, 40~60%, and 0~5%, respectively. (3) Loading conditions remarkably affected the ultimate bearing capacity of the main arch ring. Under mid-span loading and 1/4 span symmetrical loading conditions, compared to single-pour concrete encapsulation, the ultimate bearing capacity of the main arch ring with concrete encapsulated by segmented and ring-divided pouring decreased by 19.16% and 5.23%, respectively, compared to single-pour concrete encapsulation. This suggests that the non-uniformity of stress distribution in the concrete sheath can lead to reductions in the ultimate bearing capacity of the arch ring.

Electron backscatter diffraction (EBSD) technology is a powerful tool for materials characterization including crystal orientation mapping, phase identification, and strain analysis. However, it is still challenging for using EBSD to identify crystallographic defects due to the insufficient understanding of the diffraction patterns of different defect structures. In the present work, EBSD patterns of FCC-Fe with 1/2 < 110 > edge dislocation dipole and 1/6 < 11̅2 > screw dislocation quadrupole structures are simulated by the revised real space (RRS) method. Our results showed that the presence of dislocations deteriorates the overall quality of the diffraction pattern and have different effects on different Kikuchi bands and Kikuchi poles. The edges of the Kikuchi band corresponding to the edge dislocation glide plane are sharp and the diffraction details within the band are clear. The sharpness of the edges of the Kikuchi band corresponding to the crystal plane normal to the dislocation Burgers vector is reduced, but the intra-band diffraction details are clear. Other Kikuchi bands show obvious anisotropic blurring. The diffraction details of the Kikuchi pole corresponding to the screw dislocation Burgers vector are clear, the edges of the Kikuchi bands across this pole are sharp, and the diffraction details within the bands are clear in the segments close to this pole and blurred in the segments far away from it. Other Kikuchi bands and Kikuchi poles are blurred. Our results indicate that the EBSD pattern can be simulated based on the electron diffraction dynamic theory and the correlation between dislocation structure and EBSD pattern is revealed, which provides theoretical guidance for the resolution of dislocation structures by the EBSD technique., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Osmotic stress seriously limits crop yield and quality. Among plant-specific transcription factors families, the NAC family of transcription factors is extensively involved in various growth, development and stress responses. Here we identified a maize NAC family transcription factor ZmNAC2 with inducible gene expression in response to osmotic stress. The subcellular localization showed that it was localized in the nucleus and overexpression of ZmNAC2 in Arabidopsis significantly promoted seed germination and elevated cotyledon greening under osmotic stress. ZmNAC2 also enhanced stomatal closure and decreased water loss in transgenic Arabidopsis. Overexpression of ZmNAC2 activated ROS scavenging and the transgenic lines accumulated less MDA and developed more lateral roots with drought or mannitol treatment. Further RNA-seq and qRT-PCR analysis showed that ZmNAC2 up-regulated a number of genes related to osmotic stress resistance, as well as plant hormone signaling genes. All together, ZmNAC2 enhances osmotic stress tolerance by regulating multiple physiological processes and molecular mechanisms, and exhibits potential as the target gene in crop breeding to increase osmotic stress resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

N -(Anthrancen-9-ylmethyl) isoserines are useful drug intermediates but short for efficient synthesis. We herein report the synthesis of N -(anthrancen-9-ylmethyl) isoserines via a Rh 2 (Ph 3 COO) 3 (OAc) and chiral phosphoric acid (CPA) synergistically catalyzed multicomponent reaction (MCR) of N -alkyl imines, alcohols, and diazoesters. The method representing the first example of N -alkyl imines-involved MCR is featured by high atom-economy, high diastereo- and enantioselectivities, and broad substrate scope. DFT calculations on the mechanism of the MCR reveals that the hydrophobic interactions and π-π stackings between N -(anthrancen-9-ylmethyl) imines and Rh 2 (Ph 3 COO) 3 (OAc)/CPA cocatalyst is essential to the reactivity and stereocontrol. The synthetic applications of the MCR products include the semisynthesis of paclitaxel, its alkyne-tagged derivative, and β -lactam as an anticancer agent overcoming paclitaxel-resistance. We expect this work to shed light on the development of new N -alkyl imines-involved reactions and on the synthesis of drugs with isoserines as intermediates.

Introduction: Thoracoscopic minimally invasive surgery is the main method for the treatment of lung cancer. The reduction of surgical trauma can effectively reduce the intraoperative and postoperative inflammatory reaction. The aim of the study is to compare the intraoperative and postoperative inflammatory reactions in patients with non-small-cell lung cancer (NSCLC) treated by single-port thoracoscopic surgery and three-port thoracoscopic surgery., Methods: A total of 68 NSCLC patients (stages I and II) of thoracoscopic surgery were selected and randomly divided into two groups where they received either single-port thoracoscopic surgery or three-port thoracoscopic surgery. Intraoperative and postoperative serum inflammatory markers (C-reactive protein, CRP; serum amyloid A protein, SAA; and interleukin 6, IL-6) were detected using the enzyme-linked immunosorbent assay., Results: The CRP level of the single-port group was significantly lower than that of the three-port group during surgery, the first day after surgery, and third day after surgery ( P < 0.05). The level of IL-6 in the single-port group was significantly lower than that in the three-port group during surgery on the first and third days after surgery ( P < 0.05). The level of SAA in the single-port group was also significantly lower than that in the three-port group on the first and third days after surgery ( P < 0.05)., Conclusion: Compared with three-port thoracoscopic surgery, single-port thoracoscopic surgery could reduce the inflammatory response and improve the recovery of NSCLC patients. Single-port thoracoscopic surgery is worthy of further promotion in the current treatment field of NSCLC in terms of reducing intraoperative and postoperative inflammatory reactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song Liang et al.)

Objective: To assess the awareness, knowledge, and misconceptions of young people regarding long-acting reversible contraceptives (LARCs)., Design: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines of MEDLINE-Ovid, Embase, and Cumulative Index to Nursing and Allied Health Literature. A random-effects meta-analysis was performed with formal tests for heterogeneity and publication bias. Additional outcomes were summarized using thematic analysis., Setting: Not applicable., Patient(s): Adolescents and young adults (aged 12-25 years) with a uterus., Intervention(s): Not applicable., Main Outcome Measure(s): Patient-reported outcomes related to awareness, knowledge, and misconceptions of LARCs (including intrauterine devices, subdermal implants, and injections) were analyzed., Result(s): Of the 4,077 database citations, we included 40 studies encompassing 10,470 adolescents and young people. Twenty studies were eligible for meta-analysis. The pooled prevalence described that only 65.0% (95% confidence interval [CI], 51-78) of participants were aware of at least 1 type of LARC (I 2 = 100). The meta-regression noted that the region, risk of bias, gravidity, sexual history, previous LARC experience, and postsecondary education were not associated with awareness. There were numerous misconceptions regarding eligibility, safety, and usage. Notably, 62% (95% CI, 20-91) did not understand that LARCs could be used in nulliparous individuals, and 37% (95% CI, 21-56) believed that LARCs could cause infertility., Conclusion(s): There are notable knowledge gaps among adolescents and young people regarding LARCs, such as eligibility criteria, the reversibility of long-acting options, and misconceptions regarding infertility. Clinicians should specifically counsel regarding the suitability for LARCs in nulliparous populations and that LARCs do not cause infertility., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The design system based on aesthetic principles is the most representative in the field of design and has a certain significance for the research and construction of design aesthetics and the development of design education. Therefore, this paper studies the application of pattern recognition system in the field of design based on aesthetic principles and designs a new type of aesthetic principle design system based on pattern recognition in computer vision. This paper proposes pattern similarity measurement and image preprocessing technology to improve the traditional aesthetic principle design system through pattern recognition and then further refine the research of the whole system through histogram equalization and gamma correction. Finally, the MNIST dataset experiment is used to verify the effect of multicolumn convolutional neural network pattern recognition on the aesthetic principle design system. The questionnaire survey experiment in this article and the traditional comparative experiment show that 76% of the public are very satisfied with this design system based on the aesthetic principles of pattern recognition in computer vision. Also, the improved aesthetic principle system scores as high as 90-95 points., Competing Interests: The authors declare that there are no potential conflicts of interest in this study., (Copyright © 2022 Chenzhen Wang and Xinglin Li.)

Recognition of viral infections by various pattern recognition receptors (PRRs) activates an inflammatory cytokine response that inhibits viral replication and orchestrates the activation of adaptive immune responses to control the viral infection. The broadly active innate immune response puts a strong selective pressure on viruses and drives the selection of variants with increased capabilities to subvert the induction and function of antiviral cytokines. This revolutionary process dynamically shapes the host ranges, cell tropism and pathogenesis of viruses. Recent studies on the innate immune responses to the infection of human coronaviruses (HCoV), particularly SARS-CoV-2, revealed that HCoV infections can be sensed by endosomal toll-like receptors and/or cytoplasmic RIG-I-like receptors in various cell types. However, the profiles of inflammatory cytokines and transcriptome response induced by a specific HCoV are usually cell type specific and determined by the virus-specific mechanisms of subverting the induction and function of interferons and inflammatory cytokines as well as the genetic trait of the host genes of innate immune pathways. We review herein the recent literatures on the innate immune responses and their roles in the pathogenesis of HCoV infections with emphasis on the pathobiological roles and therapeutic effects of type I interferons in HCoV infections and their antiviral mechanisms. The knowledge on the mechanism of innate immune control of HCoV infections and viral evasions should facilitate the development of therapeutics for induction of immune resolution of HCoV infections and vaccines for efficient control of COVID-19 pandemics and other HCoV infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Mutations (K11E or E271K) of DEAD-box RNA helicase 24 (DDX24) were related to multi-organ venous lymphatic malformation syndrome (MOVLD). However, the relationship between these mutations and DDX24-function still remains unknown. Understanding whether K11E and E271K cause "loss-of-function" or "gain-of-function" for DDX24 is significant for related diseases. DDX24 was reported to be related to tumors closely, thus this study aims to explore how K11E and E271K affect DDX24-function in tumor proliferation. Methods: Cell lines stably expressing wild-type DDX24, K11E-DDX24, E271K-DDX24, along with vector only based on Chinese hamster ovary cells (CHO) and Balb/c tumor-bearing mice models were constructed. Then immunofluorescence staining, proliferation assay and colony formation assay in vitro and 18 F-FDG PET/CT-scan were performed. Finally, the tumor tissues were collected to perform transcriptome sequencing to predict the potential mechanism. Results: Contrasted with CHO-WT-DDX24, CHO-K11E-DDX24 or CHO-E271K-DDX24 showed a decreased number of nucleoli, a slower proliferation rate and a lower colony formation rate significantly. Moreover, mice, inoculated with CHO-K11E-DDX24 or CHO-E271K-DDX24 cells, showed lower tumor formation rate, slower tumor growth rate, better prognosis, reduced standard uptake value and K i of glucose in subcutaneous tumors. Sequencing indicated CHO-K11E-DDX24 or CHO-E271K-DDX24 caused increasing expression of TNF or chemokines and alteration in immune-related signal pathways. Conclusion: K11E or E271K mutation could lead to "loss-of-function" of DDX24 in cell proliferation and tumor bearing mice, which may be acted by non-specific immune killing to inhibit tumor growth., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A broad-spectrum antimicrobial peptide named Paracin 1.7 was produced by Lactobacillus paracasei HD1.7, which was isolated from Chinese sauerkraut juice. In this study, the influence of cocultivation on the communication mechanism of L. paracasei HD1.7 and Bacillus subtilis was investigated. The two bacterial strains were grown in monoculture and indirect coculture, and the growth of both bacteria and bacteriocin production as well as the transcriptional level of luxS in L. paracasei HD1.7 and spo0A in B. subtilis were monitored. Bacteriocin production and cell numbers were increased significantly when L. paracasei HD1.7 cells were indirectly cocultured with B. subtilis , and bacteriocin-producing L. paracasei HD1.7 can prevent the growth and sporulation of B. subtilis . After indirect coculture with B. subtilis , the expression of luxS in L. paracasei HD1.7 increased in the exponential growth phase and decreased in the stationary phase compared to monoculture. The expression of spo0A in B. subtilis dropped in the indirect coculture compared to the monoculture. It indicate that the upregulation of luxS is due to a response to a secreted compound produced by B. subtilis . The results show L. paracasei HD1.7 has an amensalism on B. subtilis , while B. subtilis has a commensalism on L. paracasei HD1.7.

Coronaviruses (CoVs) are a group of enveloped positive-sense RNA viruses and can cause deadly diseases in animals and humans. Cell entry is the first and essential step of successful virus infection and can be divided into two ongoing steps: cell binding and membrane fusion. Over the past two decades, stimulated by the global outbreak of SARS-CoV and pandemic of SARS-CoV-2, numerous efforts have been made in the CoV research. As a result, significant progress has been achieved in our understanding of the cell entry process. Here, we review the current knowledge of this essential process, including the viral and host components involved in cell binding and membrane fusion, molecular mechanisms of their interactions, and the sites of virus entry. We highlight the recent findings of host restriction factors that inhibit CoVs entry. This knowledge not only enhances our understanding of the cell entry process, pathogenesis, tissue tropism, host range, and interspecies-transmission of CoVs but also provides a theoretical basis to design effective preventive and therapeutic strategies to control CoVs infection.

Drought stress causes heavy damages to crop growth and productivity under global climatic changes. Transcription factors have been extensively studied in many crops to play important roles in plant growth and defense. However, there is a scarcity of studies regarding WRKY transcription factors regulating drought responses in maize crops. Previously, ZmWRKY79 was identified as the regulator of maize phytoalexin biosynthesis with inducible expression under different elicitation. Here, we elucidated the function of ZmWRKY79 in drought stress through regulating ABA biosynthesis. The overexpression of ZmWRKY79 in Arabidopsis improved the survival rate under drought stress, which was accompanied by more lateral roots, lower stomatal aperture, and water loss. ROS scavenging was also boosted by ZmWRKY79 to result in less H 2 O 2 and MDA accumulation and increased antioxidant enzyme activities. Further analysis detected more ABA production in ZmWRKY79 overexpression lines under drought stress, which was consistent with up-regulated ABA biosynthetic gene expression by RNA-seq analysis. ZmWRKY79 was observed to target ZmAAO3 genes in maize protoplast through acting on the specific W-boxes of the corresponding gene promoters. Virus-induced gene silencing of ZmWRKY79 in maize resulted in compromised drought tolerance with more H 2 O 2 accumulation and weaker root system architecture. Together, this study substantiates the role of ZmWRKY79 in the drought-tolerance mechanism through regulating ABA biosynthesis, suggesting its broad functions not only as the regulator in phytoalexin biosynthesis against pathogen infection but also playing the positive role in abiotic stress response, which provides a WRKY candidate gene to improve drought tolerance for maize and other crop plants.

Purpose: Performing a gynecological exam is an essential skill for physicians. While interventions have been implemented to optimize how this skill is taught in medical school, it remains an area of concern and anxiety for many medical students. To date, a comprehensive assessment of these interventions has not been done. The authors conducted a systematic review of the literature on interventions that aim to improve medical student education on gynecological exams., Method: The authors searched 6 databases (Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL Plus, Scopus, Web of Science Core Collection, and ERIC [Proquest]) from inception to August 4, 2020. Studies were included if they met the following criteria: focus on medical students, intervention with the purpose of teaching students to better perform gynecological exams, and reported outcomes/evaluation. Extracted data included study location, study design, sample size, details of the intervention and evaluation, and context of the pelvic exam. All outcomes were summarized descriptively; key outcomes were coded as subjective or objective assessments., Results: The search identified 5,792 studies; 50 met the inclusion criteria. The interventions described were diverse, with many controlled studies evaluating multiple methods of instruction. Gynecological teaching associates (GTAs), or professional patients, were the most common method of education. GTA-led teaching resulted in improvements in student confidence, competence, and communication skills. Physical adjuncts, or anatomic models and simulators, were the second most common category of intervention. Less resource-intensive interventions, such as self-directed learning packages, online training modules, and video clips, also demonstrated positive results in student comfort and competence. All studies highlighted the need for improved education on gynecological exams., Conclusions: The literature included evaluations of numerous interventions for improving medical student comfort and competence in performing gynecological exams. GTA-led teaching may be the most impactful educational tool described, though less resource-intensive interventions can also be effective., (Copyright © 2021 by the Association of American Medical Colleges.)

Background: Esophageal squamous carcinoma (ESCC) is one of the most common cancers in developing countries. However, currently there are no specific biomarkers for ESCC. This study evaluated the expression of proliferating cell nuclear antigen (PCNA), tumor suppressor protein p53, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as biomarkers for ESCC., Methods: This study included 60 clinical cases (30 ESCC and 30 non-ESCC cases that were confirmed pathologically). The expression of PCNA, p53, EGFR, and VEGF were investigated using a quantitative computerized immunohistochemistry (IHC) method. The expression level of each protein was indicated by a H-score from the quantitative analysis. Receiver operating characteristic curve (ROC) and area under curve (AUC) analyses were performed. The sensitivity and specificity of each individual protein and combinations of the proteins were calculated., Results: The H-score analysis indicated that expressions of EGFR, PCNA, and VEGF were statistically significantly higher in ESCC than non-ESCC patients; however, p53 was not. The panels of combinations of these proteins were more sensitive than that of any single protein. In the triplicate combination, the AUC prediction probability increased to 0.86, while the single protein AUC prediction probabilities were 0.74 (EGFR), 0.80 (PCNA), and 0.70 (VEGF)., Conclusions: The high expression of PCNA, EGFR, and VEGF suggests that they are potential biomarkers for ESCC. The combination of these biomarkers may provide targets for molecular therapy and molecular imaging., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2950). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

A novel copper hydroxy phosphate@MOF composite DMP-Cu decorated by 2, 5-dimercapto-1, 3, 4-thiadiazol was facilely prepared and characterized. A dispersive SPE strategy using DMP-Cu as adsorbent combined with atomic fluorescence spectroscopy was developed for the selective capture of trace total mercury in rice sample. The adsorption mechanism showed that the Hg 2+ removal process was fitted with pseudo second-order kinetics and the Langmuir adsorption model. The adsorbent was easy to be regenerated and the maximum adsorption capacity for the removal of Hg 2+ was 249.5 mg g -1 at the optimal pH of 4. X-ray photoelectron spectroscopy and Raman spectra verified the selective and strong interaction between Hg 2+ and thiol/nitrogen-containing functional groups of DMTZ on DMP-Cu. The trace total mercury in rice samples was determined with detection limit of 0.0125 ng mL -1 and relative standard deviation below 6%. The high recoveries were obtained in range of 98.8-109% for the spiked rice samples., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Obstetricians and gynaecologists are among the highest risk specialties for burnout. There is growing evidence that physician burnout can be both prevented and reduced. We sought to characterize the evidence base for interventions related to the prevention and treatment of burnout in obstetrics and gynaecology DATA SOURCES: We conducted a scoping review following PRISMA guidelines of 5 databases: (Medline-OVID, EMBASE, CINAHL, ClinicalTrials.gov, and PsycInfo) from inception to March 17, 2020. Citations of relevant articles were hand-searched to maximize sensitivity., Study Selection: All interventional study designs were included. The target study population was obstetrics and gynaecology residents, learners, or staff. Published conference posters, papers, and abstracts were eligible for inclusion., Data Extraction and Synthesis: All extraction and descriptive analysis was completed by two independent reviewers. Outcomes were summarized descriptively. Appraisal was completed using the Cochrane Risk of Bias tool and Risk of Bias Assessment tool for Non-randomized Studies., Results: Of the 1540 original database citations, 20 studies met our inclusion criteria. A total of 589 obstetrics/gynaecology participants were included. While there was an overall a lack of research in the field, there were several promising interventions that target residents. There were a combination of preventative interventions (e.g. yoga, nutritional programs, or narrative medicine initiatives) as well as treatments (e.g. counselling appointments or debrief sessions). The vast majority of these interventions focused on individual-specific interventions rather than structural changes. In addition, the majority of interventions appeared to be "proof of concept" and feasability-related studies, with many studies published as conference abstracts rather than peer-reviewed journal publications., Conclusions: Institutions should continue to implement interventions that address burnout in obstetrics and gynaecology. Further research is required on long-term outcomes of interventions as well as structural strategies., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Though cervical cancer is one of the leading causes of cancer-related death globally, its incidence is nearly entirely preventable. Young people have been an international priority for screening as this population has historically been under-screened. However, in both high-income and low-income countries, young people have not been screened appropriately according to country-specific guidelines. The aim of this systematic review was to systematically characterize the existing literature on barriers and facilitators for cervical cancer screening (CCS) among adolescents and young people globally., Methods: We conducted a systematic review following PRISMA guidelines of three key databases: Medline-OVID, EMBASE, and CINAHL. Supplementary searches were done through ClinicialTrials.Gov and Scopus. Databases were examined from 1946 until the date of our literature searches on March 12th 2020. We only examined original, peer-reviewed literature. Articles were excluded if they did not specifically discuss CCS, were not specific to individuals under the age of 35, or did not report outcomes or evaluation. All screening, extraction, and synthesis was completed in duplicate with two independent reviewers. Outcomes were summarized descriptively. Risk of bias for individual studies was graded using an adapted rating scale based on the Risk of Bias Instrument for Cross-Sectional Surveys of Attitudes and Practices., Results: Of the 2177 original database citations, we included 36 studies that met inclusion criteria. The 36 studies included a total of 14,362 participants, and around half (17/36, 47.2%) of studies specifically targeted students. The majority of studies (31/36, 86.1%) discussed barriers and facilitators to Pap testing specifically, while one study analyzed self-sampling (1/36, 2.8%), one study targeted HPV DNA testing (1/36, 2.8%), and the remainder (4/36, 11.1%) were not specified. Our systematic review found that there are three large categories of barriers for young people: lack of knowledge/awareness, negative perceptions of the test, and systemic barriers to testing. Facilitators included stronger relationships with healthcare providers, social norms, support from family, and self-efficacy., Conclusion: There are unique barriers and facilitators that affect CCS rates in adolescents and young people. Health systems and healthcare providers worldwide should address the challenges for this unique population.

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon-induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging (SARS-CoV-2).

Chiral metal-organic frameworks (CMOFs) have been explored as potential chiral stationary phases (CSPs) for chiral high performance liquid chromatography (HPLC). However, their application is still hindered by the low column efficiency, high back pressure and the difficulty in column packing due to the irregular shapes and wide size distributions of CMOF particles. Here we report an efficient one-pot method for the immobilization of chiral MOF [Cu 2 ((+)-Cam) 2 Dabco] (Cu 2 C 2 D) onto microspheric silica particles, generating a uniform core-shell microsphere with SiO 2 @CMOF@CMOF morphology as CSP packing material. Significantly, the shell thickness and the corresponding column efficiency could be rationally regulated by controlling the growth cycles of [Cu 2 ((+)-Cam) 2 Dabco]. The structure of developed core-shell microspheres were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), powder X-ray diffraction (PXRD), N 2 adsorption experiments, infrared spectroscopy (FT-IR) and thermogravimetric analysis. Mechanism involved in the chromatographic separation is the multi-interactions including hydrophobic and hydrogen-bonding, etc. Based on these interactions, successful separation could be achieved among different types of racemic compounds such as carboxylic acid, ketones and phenols under normal phase liquid chromatography (NPLC) condition. In addition, the relative standard deviation (RSD%) value of the retention time for TNPTO was below 1.1% (n = 5), indicating the good repeatability and stability of the chiral SiO 2 @Cu 2 C 2 D-2 column for HPLC enantioseparation. The results reveal that the CMOF coating approach is convenient to fabricate CSP with pre-designed functions of good recognition performance and to facilitate the evolution of CSP in chiral HPLC. Furthermore, the SiO 2 @Cu 2 C 2 D-2 column was successfully employed for the determination of the enantiomeric excess value for TNPTO in the asymmetric Michael addition reaction., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Treatment for triple-negative breast cancer (TNBC) remains a significant challenge due to a lack of targeted therapies. While photodynamic therapy (PDT) has been utilized as a treatment approach for several types of cancer, oxyphotodynamic therapy (OPDT) is a novel method that improves treatment efficacy by increasing local oxygen concentration. Metformin (MET) has been demonstrated utility as an anti-tumor agent by acting through the adenosine monophosphate-activated protein kinase (AMPK) pathway. We hypothesized that MET in combination with heme, a byproduct of 5-aminolevulinic acid (ALA), may increase cytotoxicity for cancer treatment. This study aimed to investigate the synergistic effect of MET and ALA with PDT or OPDT on TNBC tumorigenic cells., Methods: The treatment efficacy and phototoxicity of PDT or OPDT were determined using a cell viability assay. PDT/OPDT experiments were carried out in nine groups based on different combinations and concentrations of ALA and/or MET. To calculate the synergistic effect by compuSyn soft for different groups, cells were incubated with ALA and/or MET at the following concentrations (0, 0.25, 0.5,1, 2, 4, 8, 16, 24, and 32 mM). The fluorescence of ALA-induced protoporphyrin IX (PpIX) and MitoTracker Green were observed under a confocal microscope., Results: The optimized therapeutic concentration ratio of ALA and MET was determined to be 1:1. The inhibition of cancer growth (IC 50 ) for each group was 14.03, 10.62, 7.71, 18.27, 22.09, 23.96, 4.57, 10.20, and 8.18 mM, respectively. The combination index (CI) values (fa =0.5) of the last three combination groups (groups 7, 8, and 9) were 0.44, 1.70, and 1.47, respectively. PpIX fluorescence intensity of group 9 (ALA-MET-OPDT group) remained the highest among all groups, indicating an enhanced therapeutic effect., Conclusions: This study introduces OPDT as a novel anti-tumor therapy for TNBC. Furthermore, the combined use of ALA and MET had a synergistic anti-tumor effect in TNBC cells when combined with OPDT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5704). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry. IMPORTANCE Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates the entry of several human-pathogenic viruses, including human immunodeficiency virus, influenza A virus, and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection., (Copyright © 2020 Zhao et al.)

The COVID-19 pandemic has caused an unprecedented global public health and economic crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, unlike the SARS-CoV-2-like coronaviruses (CoVs) identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models. IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2., (Copyright © 2020 Zhao et al.)

All kinds of mutagenic factors may cause physiological, biochemical and genetic changes of all organisms. To characterize their characteristic biology effects, the concept of Relaxation Time (RT) was introduced for the first time, and the specific process was as follows. After mutation of organisms, the offsprings will be continuingly cultured (or cultivated) to the next generation (Rx). Once a biological effect began to show no significant difference compared to the untreated controls, the Rx was defined as the RT of the effect. In this paper, three kinds of mutagenic factors were selected to treat the seeds or seedlings of Astragalus sinicus L., subsequently, the corresponding RT was calibrated. The results showed that the RT was diverse not only among different biological effects but also among different mutagenic factors. For the RT of chemical mutagens and gamma rays, most of which are concentrated on R 1 , whereas the heavy ion beams have significant differences among different tracks. Among biological effects, the SOD activity and superoxide anion free radical content in the Peak region are more prominent, and their RT reaches R 3 and R 4 , respectively. Thus, the RT may characterize the characteristic biological effects from differently mutagenic factors.

Aptamers, because of their outstanding merits including simple synthesis and easy modification, have been widely used as antibody alternatives to construct novel immunosandwich assays. Dual aptamer-based sandwich assays exhibit multiple advantages over conventional immunosandwich assays and single aptamer-based sandwich assays. However, their construction is hampered by the limited knowledge of binding orthogonality of aptamers reported in the literature. Herein, we present a new strategy for conveniently constructing an orthogonal dual aptamer-based plasmonic immunosandwich assay (odA-PISA) for probing proteins in complex samples and living animals. An orthogonal aptamer pair was first efficiently selected from the aptamers reported in the literature by affinity capillary electrophoresis. Then, a target protein-capturing gold thin-layer-coated probe and silver nanoparticle-based Raman labeling nanotags were conveniently prepared with the selected aptamers and used to construct the assay. The double aptamers used ensured the specificity, whereas the plasmonic coupling effect between the target-capturing probe and the generated Raman nanotags significantly enhanced the Raman signal intensity, providing high sensitivity. As a proof of principle, alkaline phosphatase (ALP) was used as the target. The constructed odA-PISA exhibited high specificity and high sensitivity toward ALP, giving cross-reactivity ≤ 4.2% and the limit of detection of 3.8 pM (S/N = 4). The quantitative determination of ALP in human serum and probing ALP in tumor-bearing mice were achieved, showing the great application potential of the method. This strategy is widely applicable to other protein disease markers. Therefore, it opened a new access to the construction of sensitive dual aptamer-based sandwich assays for real-world applications, particularly disease diagnosis.

Chiral metal-organic frameworks (CMOFs),[Zn(L-mal)(H 2 O) 2 ] n were prepared by using zinc oxide instead of the traditional metal inorganic salt as the zinc source, and their chiral separation performance was investigated. Equal amounts of ZnO and L-malic acid were dissolved in H 2 O, and[Zn(L-mal)(H 2 O) 2 ] n were obtained by allowing the mixture to stand at room temperature for 24 h. Then, 100 mg[Zn(L-mal)(H 2 O) 2 ] n as the adsorbent was added to 250 μL 1 g/L 2,2'-furoin racemate, and 4.5 mL isopropanol and 1 mL methanol were selected as the extraction solvent and elution solvent, respectively, for selective adsorption experiments. The final filtrate was analyzed by high performance liquid chromatography (HPLC). The results showed that[Zn(L-mal)(H 2 O) 2 ] n exhibited better selective adsorption ability for R -2,2'-furoin with 20% enantiomeric excess (ee). This work provides a new method for the green preparation of CMOF and expands its application in the field of chiral separation.

In order to improve the antitumor potency of the natural product evodiamine, novel boron-containing evodiamine derivatives were designed by incorporating boronic acid and boronate as trigger units. Boronate derivative 13a could be triggered by reactive oxygen species (ROS) in the HCT116 colon cancer cell line and showed excellent antitumor activity in vitro and in vivo . It induced apoptosis in HCT116 cancer cells in a dose-dependent manner and cell growth arrest at the G2 phase., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

As a proof-of-concept, an l-phenylalanine-based metal-organic framework Zn-MOF, namely [Zn2(l-Phe)2(bpe)2]n, was designed for experimentally revealing the chiral recognition mechanism of alanine and leucine by means of 13C CP MAS NMR spectroscopy, X-ray photoelectron spectroscopy and control experiments.

Background: The mechanisms mediating the impacts of fetal growth restriction (FGR) on follicular development are commonly studied in mouse/rat models, where ovarian development occurs largely during the early postnatal period. These models have shown that FGR is associated with premature follicle loss, early pubertal onset, and accelerated ovarian aging. Whether the same occurs in precocious species is unknown., Objective: Since guinea pig follicle development occurs in utero in a manner consistent with human ovarian development, we sought to determine whether FGR had similar impacts on guinea pig ovarian development., Methods: Dunkin-Hartley guinea pig dams were randomized to receive a control (CON) or a nutrient-restricted diet (FGR) prior to conception until weaning. Offspring ovaries were collected at prepubertal (postnatal day [P] 25) and young adult (P110) time points., Results: Prepubertal offspring exposed to FGR showed little differences in ovarian transcript levels and follicle counts. Young adult FGR offspring, however, showed reductions in the number of transitioning, primary, and antral follicles, as well as corpora lutea. This loss in follicles was associated with reduced insulin-like growth factor receptor and growth differentiation factor-9 messenger RNA levels in FGR P110 offspring compared to CON., Conclusion: We demonstrate that FGR in guinea pigs is accompanied by perturbations in signaling pathways essential for proper follicle growth and manifests as reductions in growing follicles in offspring, but these changes do not manifest until postpuberty. These data support the fact that accelerated reproductive maturation/aging is a conserved phenotype that is associated with in utero nutritional adversity.

Nucleic acid aptamers, as useful alternatives of antibodies, have found a large range of promising applications such as affinity separation and bioassays. The screening of aptamers is critical for their applications. Aptamers are often screened by an in vitro methodology called SELEX (systematic evolution of ligands by exponential enrichment). Although numerous SELEX methods have been established to facilitate the selection, new efficient selection methods are still much needed. Molecularly imprinted polymers, which are antibody alternatives at the material level and competitors of aptamers, have not been used as a platform for aptamer selection yet so far. In this study, a glycan-imprinted magnetic nanoparticles (MNPs)-based SELEX was developed to efficiently screen aptamers against glycoproteins. Glycan-imprinted MNPs were used as an affinity interface to bind target glycoprotein, and then the target glycoprotein-bound MNPs were used as an affinity substrate for aptamer selection. The glycan-imprinted MNPs were synthesized by a state-of-the-art imprinting approach called boronate affinity controllable oriented surface imprinting. The glycan-imprinted MNPs exhibited high affinity and specificity and therefore allowed preferential binding toward target glycoproteins while excluding unwanted species. Two representative glycoproteins, including RNase B and transferrin, were employed as target glycoproteins, and aptamers with high affinity and specificity toward the two target glycoproteins were screened out in 3 rounds. This method exhibited some merits, such as high affinity, fast speed, and avoiding negative screening. Therefore, the glycan-imprinted MNP-based SELEX approach holds great values for the efficient screening of high-performance aptamers.

Plasmonic nanomaterials have been widely used for photothermal therapy (PTT) of cancer, but their recognition specificity remains challenging. We prepared monosaccharide-imprinted gold nanorods (AuNRs) for targeted cancer PTT, using sialic acid (SA) as a representative monosaccharide. The SA-imprinted AuNRs exhibited good specificity, enabling the killing of cancer cells without damaging healthy cells.

Periploca sepium Bunge is a traditional medicinal plant, whose root bark is important for Chinese herbal medicine. Its major bioactive compounds are C21 steroids and periplocin, a kind of cardiac glycoside, which are derived from the steroid synthesis pathway. However, research on P. sepium genome or transcriptomes and their related genes has been lacking for a long time. In this study we estimated this species nuclear genome size at 170 Mb (using flow cytometry). Then, RNA sequencing of four different tissue samples of P. sepium (leaves, roots, adventitious roots, and calli) was done using the sequencing platform Illumina/Solexa Hiseq 2,500. After de novo assembly and quantitative assessment, 90,375 all-transcripts and 71,629 all-unigenes were finally generated. Annotation efforts that used a number of public databases resulted in detailed annotation information for the transcripts. In addition, differentially expressed genes (DEGs) were identified by using digital gene profiling based on the reads per kilobase of transcript per million reads mapped (RPKM) values. Compared with the leaf samples (L), up-regulated genes and down-regulated genes were eventually obtained. To deepen our understanding of these DEGs, we performed two enrichment analyses: gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Here, the analysis focused upon the expression characteristics of those genes involved in the terpene metabolic pathway and the steroid biosynthesis pathway, to better elucidate the molecular mechanism of bioactive steroid synthesis in P. sepium . The bioinformatics analysis enabled us to find many genes that are involved in bioactive steroid biosynthesis. These genes encoded acetyl-CoA acetyltransferase (ACAT), HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), mevalonate kinase (MK), phosphomevalonate kinase (PMK), mevalonate diphosphate decarboxylase (MDD), isopentenylpyrophosphate isomerase (IPPI), farnesyl pyrophosphate synthase (FPS), squalene synthase (SS), squalene epoxidase (SE), cycloartenol synthase (CAS), sterol C-24 methyltransferase (SMT1), sterol-4alpha-methyl oxidase 1 (SMO1), sterol 14alpha-demethylase (CYP51/14-SDM), delta(14)-sterol reductase (FK/14SR), C-8,7 sterol isomerase (HYD1), sterol-4alpha-methyl oxidase 2 (SMO2), delta(7)-sterol-C5(6)-desaturase (STE1/SC5DL), 7-dehydrocholesterol reductase (DWF5/DHCR7), delta (24)-sterol reductase (DWF1/DHCR24), sterol 22-desaturase (CYP710A), progesterone 5beta-reductase (5β-POR), 3-beta-hydroxysteroid dehydrogenase (3β-HSD). This research will be helpful to further understand the mechanism of bioactive steroid biosynthesis in P. sepium , namely C21 steroid and periplocin biosynthesis.

Heavy ion beams have many exciting applications, including radiotherapy of deep-seated tumors and simulation tests of space irradiation for astronauts. These beams often use a feature that concentrates the energy deposition largely along the end of the energy pathway, leading to different distributions of biological effects along the axial direction. Currently, there is relatively little information regarding the radial directional difference of biological effects along the heavy ion paths. This study utilized a filter membrane that was quantatively applied with cells to demonstrate a 3D distribution model of irradiation on biological effects in living organisms. Some results have indicated that there is excitatory effect on the non-irradiated regions with energetic ions, which may give new insights into the distribution of biological effects along the paths of heavy ion beams with mid-high energy.

Glycerol is a byproduct during biodiesel production. It is an important feedstock for fermentation due to its low price and high reduced status. Multiple genes of the glycerol utilization pathway were modulated in a previously engineered high β-carotene producing Escherichia coli strain CAR015 to enhance glycerol utilization capability for improving isoprenoids production. The glpR gene, encoding glycerol 3-phosphate repressor, was firstly deleted. The glpFK, glpD and tpiA genes were then modulated by three artificial regulatory parts, M1-37, M1-46 and M1-93, respectively. β-carotene titer reached 64.82 mg/L after modulating glpD with M1-46, which was 4.86 times higher than that of CAR015, and glycerol consumption rate also increased 100%. Modulating tpiA led to a little increase of β-carotene titer, whereas modulating glpFK led to a little decrease of β-carotene titer. This demonstrated that GlpD was a rate-limiting step in glycerol utilization pathway. Q-PCR of glpF, glpK, glpD and tpiA results showed that decrease the transcription level of glpF, glpK, glpD, or decrease the transcription level of tpiA could increase the cell growth and β-carotene production, probably for the decrease of methylglyoxal toxicity. Modulating glpD and tpiA genes in combination resulted in the best strain Gly003, which produced 72.45 mg/L β-carotene with a yield of 18.65 mg/g dry cell weight. The titer was 5.23 and yield 1.99 times of that of the parent strain CAR015. Our work suggested that appropriate activation of glpD and tpiA genes in glycerol utilization pathway could effectively improve β-carotene production. This strategy can be used for production of other terpenoids in E. coli.

Capillary electrophoresis (CE) and magnetic beads have been widely used for the selection of aptamers owing to their efficient separation ability. However, these methods alone are associated with some apparent drawbacks. CE suffers from small injection volumes and thereby only a limited amount of aptamer can be collected at each round. While the magnetic beads approach is often associated with tedious procedure and nonspecific binding. Herein we present a hybrid approach that combines the above two classical aptamer selection methods to overcome the drawbacks associated with these methods alone. In this hybrid method, one single round selection by boronate affinity magnetic nanoparticles (BA-MNPs) was first performed and then followed by a CE selection of a few rounds. The BA-MNPs-based selection eliminated nonbinding sequences, enriching effective sequences in the nucleic acid library. While the CE selection, which was carried out in free solutions, eliminated steric hindrance effects in subsequent selection. Two typical glycoproteins, Ribonuclease B (RNase B) and alkaline phosphatase (ALP), were used as targets. This hybrid method allowed for efficient selection of glycoprotein-binding aptamers within 4 rounds (1 round of BA-MNPs-based selection and 3 rounds of CE selection) and the dissociation constants reached 10 -8 M level. The hybrid selection approach exhibited several significant advantages, including speed, affinity, specificity, and avoiding negative selection. Using one of the selected ALP-binding aptamers as an affinity ligand, feasibility for real application of the selected aptamers was demonstrated through constructing an improved enzyme activity assay.

Förster resonance energy transfer (FRET) has been essential for many applications, in which an appropriate donor-acceptor pair is the key. Traditional dye-to-dye combinations remain the working horses but are rather nonspecifically susceptive to environmental factors (such as ionic strength, pH, oxygen, etc.). Besides, to obtain desired selectivity, functionalization of the donor or acceptor is essential but usually tedious. Herein, we present fluorescent poly(m-aminophenylboronic acid) nanoparticles (poly(mAPBA) NPs) synthesized via a simple procedure and demonstrate a FRET scheme with suppressed environmental effects for the selective sensing of cis-diol biomolecules. The NPs exhibited stable fluorescence properties, resistance to environmental factors, and a Förster distance comparable size, making them ideal donor for FRET applications. By using poly(mAPBA) NPs and adenosine 5'-monophosphate modified graphene oxide (AMP-GO) as a donor and an acceptor, respectively, an environmental effects-suppressed boronate affinity-mediated FRET system was established. The fluorescence of poly(mAPBA) NPs was quenched by AMP-GO while it was restored when a competing cis-diol compounds was present. The FRET system exhibited excellent selectivity and improved sensitivity toward cis-diol compounds. Quantitative inhibition assay of glucose in human serum was demonstrated. As many cis-diol compounds such as sugars and glycoproteins are biologically and clinically significant, the FRET scheme presented herein could find more promising applications.

We present a new strategy, called dual-template docking oriented molecular imprinting (DTD-OMI), for facile and highly efficient imprinting within mesoporous materials. As compared with bulk imprinting, which is a widely used strategy, DTD-OMI did not require additional steps, but provided significantly improved imprinting efficiency and binding properties.

Boronate affinity materials, as effective sample enrichment sorbents for glycoproteomic analysis, have attracted increasing attention in recent years. However, most of boronate affinity materials suffer from an apparent limitation, limited binding strength. As a result, extraction of glycoproteins of trace concentration is rather difficult or impossible. In this study, we present a high boronate avidity monolithic capillary. Branched polyethyleneimine (PEI) was used as a scaffold to amplify the number of boronic acid moieties. While 2,4-difluoro-3-formyl-phenylboronic acid (DFFPBA), which exhibited ultrahigh affinity toward cis-diol-containing compounds, was employed as an affinity ligand. Due to the PEI-assisted synergistic multivalent binding, the monolithic column exhibited high boronate avidity toward glycoproteins, with binding constants of 10(-6)-10(-7)M. Such binding strength was the highest among already reported boronic acid-functionalized materials that can be used for glycoproteomic analysis. Besides, the boronate avidity monolithic column exhibited one additional beneficial feature, lowered binding pH (≥6.5). These features greatly favored the selective enrichment of trace glycoproteins from real samples. The feasibility for practical applications was demonstrated with the selective enrichment of trace glycoproteins in human saliva. As compared with other boronate avidity/affinity materials, the boronate avidity monolithic capillary exhibited the best performance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The neurotoxicity of β-amyloid protein (Aβ) contributes significantly to the pathogenesis of Alzheimer's disease (AD), and hence the attractive therapeutic strategies focusing on the modulation of Aβ-induced neurotoxicity are warranted. The present study aims to investigate the neuroprotection and underlying mechanisms by which Salvia miltiorrhiza Bunge (Lamiaceae) extract (SME) protects against Aβ25-35-induced apoptosis in SH-SY5Y cells. 2h Pre-treatment of SH-SY5Y cells with SME (0.01, 0.1 or 0.2mg raw herb/ml) concentration-dependently attenuated Aβ25-35-induced cell death, as evidenced by the increase in cell viability and decrease in neuronal apoptosis. In addition, SME suppressed the increased intracellular reactive oxygen species levels, decreased the protein expression of cleaved caspase-3, cytosolic cytochrome c, and Bax/Bcl-2 ratio. These findings taken together suggest that SME provides substantial neuroprotection against Aβ25-35-induced neurotoxicity in SH-SY5Y cells, at least in part, via inhibiting oxidative stress and attenuating the mitochondria-dependent apoptotic pathway. The approach used in this study may also be useful for the screening of therapeutic agents for AD and other related neurodegenerative disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Glycyrrhiza uralensis has long been used as a flavoring and sweetening agent in food products. In the last ten years, suspensions of Glycyrhiza cells have been successfully established. However, there is no report of full metabolic profiling research on these cells. To identify their composition we used HPLC-DAD coupled with ESI(+/-)-MS (n) to compare the constituents of cultured Glycyrhiza (CG) cells with those the native cells (NG). We identified 60 compounds including flavonoids, phenols, and triterpenoids. Among these compounds, 42 occurred both in NG and CG, nine were present in NG only and nine were present in CG alone. The number of the triterpenoid aglycones without glycones in CG was smaller than that in NG. The number of flavanone, isoflavone, isoflavan, and benzenoid compounds was also smaller in CG than that in NG, whereas the number of pterocarpans was much higher. Although differences existed between CG and NG, the extract of CG was similar to that of NG. With the development of cell suspension culture-based biotransformation, cell culture of Glycyrrhiza has the potential to be more profitable than field cultivation in some areas.