Design, synthesis and bioactivity evaluation of novel monomethyl auristatin F analogues.

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.

Dietary Immunoglobulin Y by Targeting Both GbpB and GtfB Enhances the Anticaries Effect in Rats.

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.

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines.

Herein, we report a visible-light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε-amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this multicomponent reaction protocol.

Efficacy of non-pharmacological interventions for primary dysmenorrhoea: a systematic review and Bayesian network meta-analysis.

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.

Research and Progress of Inorganic Infrared Electrochromic Materials and Devices.

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.

Brave the Wind and the Waves: Discovering Robust and Generalizable Graph Lottery Tickets.

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.

High-Performance and Stability Electrochromic Devices with a Water Isotopologue.

In this report, an ammonium metatungstate (AMT) and ferrous chloride [Fe(II)Cl2] electrochromic liquid (ECL) was synthesized using a hydrothermal method, with D2O used as the solvent instead of H2O. The results show that the use of D2O 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/cm2. Hydrogen bonds in D2O solutions are expected to exhibit stronger forces compared to those in regular H2O solutions. Therefore, we hypothesize that enhancing the strength of hydrogen bonds in H2O solutions is an effective approach for improving the performance and stability of electrochromic solutions.

Reduced neutralization and Fc effector function to Omicron subvariants in sera from SARS-CoV-1 survivors after two doses of CoronaVac plus one dose subunit vaccine.

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.

Characterization of CCoV-HuPn-2018 spike protein-mediated viral entry.

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.

Evolution Law of Concrete Interface Stress of Rigid-Frame Arch under Construction and Its Impact on Ultimate Load-Bearing Capacity.

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.

EBSD patterns simulating multilayer twins based on dynamical theory of electron diffraction.

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.

EBSD patterns simulation of dislocation structures based on electron diffraction dynamic theory.

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.

Maize transcription factor ZmNAC2 enhances osmotic stress tolerance in transgenic Arabidopsis.

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.

Rh2(Ph3COO)3(OAc)/Chiral Phosphoric Acid Cocatalyzed N-Alkyl Imines-Involved Multicomponent Reactions Yielding N-(Anthrancen-9-ylmethyl) Isoserines as Drug Intermediates.

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 Rh2(Ph3COO)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 Rh2(Ph3COO)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 ß-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.

Comparison of Inflammatory Cytokine Levels between Single-Port and Three-Port Thoracoscopic Lobectomy in the Treatment of Non-Small-Cell Lung Cancer.

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.

The Application of Pattern Recognition System in Design Field Based on Aesthetic Principles.

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.

Awareness, knowledge, and misconceptions of adolescents and young people regarding long-acting reversible contraceptives: a systematic review and meta-analysis.

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 (I2 = 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.

Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity.

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 18F-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 Ki 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.

Interferon Control of Human Coronavirus Infection and Viral Evasion: Mechanistic Insights and Implications for Antiviral Drug and Vaccine Development.

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.

Bacteriocin production and inhibition of Bacillus subtilis by Lactobacillus paracasei HD1.7 in an indirect coculture system.

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.