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Backgrounds: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA., Methods: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models., Results: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935., Conclusion: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation., (© 2024 Wiley Periodicals LLC.)

Drug resistance is the primary contributor to the high mortality rate of ovarian cancer (OC). The loss of BRCA1 /2 function is linked to drug sensitivity in OC cells. The aim of this study is to enhance the drug sensitivity of OC cells by inducing BRCA1 dysfunction through promoter epigenetic editing. Epigenetic regulatory regions within the BRCA1 promoter, affecting gene expression, were initially discerned through analysis of clinical samples. Subsequently, we designed and rigorously validated epigenetic editing tools. Ultimately, we evaluated the cisplatin and olaparib sensitivity of the OC cells after editing. The BRCA1 promoter contains two CpG-rich regions, with methylation of the region covering the transcription start site (TSS) strongly correlating with transcription and influencing OC development, prognosis, and homologous recombination (HR) defects. Targeting this region in OC cells using our designed epigenetic editing tools led to substantial and persistent DNA methylation changes, accompanied by significant reductions in H3K27ac histone modifications. This resulted in a notable suppression of BRCA1 expression and a decrease in HR repair capacity. Consequently, edited OC cells exhibited heightened sensitivity to cisplatin and olaparib, leading to increased apoptosis rates. Epigenetic inactivation of the BRCA1 promoter can enhance cisplatin and olaparib sensitivity of OC cells through a reduction in HR repair capacity, indicating the potential utility of epigenetic editing technology in sensitization therapy for OC.

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal-organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems.

Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8 + T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa., Competing Interests: The lipid A1A3 is described in a Chinese patent CN114105799B. ZGF is the inventor of patent application CN114105799B, which covers a method for the synthesis of cationic lipids. The remaining authors declare that they have no competing interests., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

The understanding of the reaction mechanism of CO 2 electroreduction (CO 2 RR) is essential for the precise design of catalysts for specific products with high selectivity. In this work, combined with the computational hydrogen electrode model and kinetic energy barrier calculations, CO 2 RR pathways on Cu(100) and Al 1 Cu 3 (100) are intensively investigated. The free energy barrier of the rate-determining step of ethylene formation is reduced from 1.08 eV for *CCOH formation on Cu(100) to 0.51 eV for *CH 2 OCHOH formation on Al 1 Cu 3 (100) and enhances the catalytic activity. The reaction free energy of *CO-*CO coupling is remarkably reduced from 0.86 eV on Cu(100) to -0.43 eV on Al 1 Cu 3 (100) and the coupling barrier is reduced from 0.97 to 0.37 eV, suppressing the production of gas phase CO and enhancing the production of C 2 products. Furthermore, the selectivity toward C-O breaking of *CH 2 CHOH on Cu(100) and *CH 2 CH 2 OH on Al 1 Cu 3 (100) ensures high selectivity toward ethene rather than ethanol.

Purpose: This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis., Methods: We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves., Results: A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs . I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance., Conclusion: Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis., 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 © 2024 Lei, Hua, Mao, Cui, Mao, Yang and Li.)

In the early stage of the nematode Caenorhabditis elegans embryogenesis, the zygote divides asymmetrically into a symmetric fast lineage and an asymmetric slow lineage, producing 16 and 8 cells respectively almost at the same time, followed by the onset of gastrulation. It was recently reported that this cell division pattern is optimal for rapid cell proliferation. In this work, we compare the cell lineages of 9 nematode species, revealing that this pattern is conserved for >60 million years. It further suggests that such lineage design has an important functional role and it might speed up embryonic development in the nematode kingdom, not limited to C. elegans , and independent of the maternal-zygotic transition dynamics., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Catalytic reduction of carbon dioxide into high-value-added products, such as methanol, is an effective approach to mitigate the greenhouse effect, and improving Co-based catalysts is anticipated to yield potential catalysts with high performance and low cost. In this study, based on first-principles calculations, we elucidate the promotion effects of surface *NH x ( x = 1, 2, and 3) on the carbon dioxide hydrogenation to methanol from both activity and selectivity perspectives on Co-based catalysts. The presence of *NH x reduced the energy barrier of each elementary step on Co(100) by regulating the electronic structure to alter the binding strength of intermediates or by forming a hydrogen bond between surface oxygen-containing species and *NH x to stabilize transition states. The best promotion effect for different steps corresponds to different *NH x . The energy barrier of the rate-determining step of CO 2 hydrogenation to methanol is lowered from 1.55 to 0.88 eV, and the product selectivity shifts from methane to methanol with the assistance of *NH x on the Co(100) surface. A similar phenomenon is observed on the Co(111) surface. The promotion effect of *NH x on Co-based catalysts is superior to that of water, indicating that the introduction of *NH x on a Co-based catalyst is an effective strategy to enhance the catalytic performance of CO 2 hydrogenation to methanol.

Gibberellin (GA) is an important hormone, which is involved in regulating various growth and development. GA biosynthesis pathway and synthetase have been basically clarified. Gibberellin 3β hydroxylase (GA3ox) is the key enzyme for the synthesis of various active GA. There are two GA3ox genes ( OsGA3ox1 and OsGA3ox2 ) in rice, and their physiological functions have been preliminarily studied. However, it is not clear how they work together to synthesize active GA to regulate rice development. In this study, the knockout mutants ga3ox1 and ga3ox2 were obtained by CRISPR/Cas9 technology. The pollen fertility of ga3ox1 decreased significantly, while the plant height of ga3ox2 decreased significantly. It shows that OsGA3ox1 is necessary for normal pollen development, while OsGA3ox2 is necessary for stem and leaf elongation. Tissue expression analysis showed that OsGA3ox1 was mainly expressed in unopened flowers, while OsGA3ox 2 was mainly expressed in unexpanded leaves. The GA in different tissues of wild type (WT), and two ga3ox mutants were detected. It was found that pollen fertility is most closely related to the content of GA 7 , and plant height is most closely related to the content of GA 1 . It was found that OsGA3ox1 catalyzes GA 9 to GA 7 in flowers, which is closely related to pollen fertility; OsGA3ox2 catalyzes the GA 20 to GA 1 in unexpanded leaves, thereby regulating plant height; OsGA3ox1 catalyzes the GA 19 to GA 20 in roots, regulating the generation of GA 3 . OsGA3ox1 and OsGA3ox2 respond to developmental and environmental signals, and cooperate to synthesize endogenous GA in different tissues to regulate rice development. This study provides a reference for clarifying its role in GA biosynthesis pathway and further understanding the function of OsGA3ox .

Background: Xylo-oligomers are a kind of high value-added products in biomass fractionation. Although there are several chemical methods to obtain xylo-oligomers from biomass, the reports about the deep eutectic solvents (DESs)-mediated co-production of xylo-oligomers and fermentable sugars and the related kinetic mechanism are limited., Results: In this work, glycolic acid-based DESs were used to obtain xylo-oligomers from corncob. The highest xylo-oligomers yield of 65.9% was achieved at 120 °C for 20 min, of which the functional xylo-oligosaccharides (XOSs, DP 2-5) accounted for up to 31.8%. Meanwhile, the enzymatic digestion of cellulose and xylan in residues reached 81.0% and 95.5%, respectively. Moreover, the addition of metal inorganic salts significantly accelerated the hydrolysis of xylan and even the degradation of xylo-oligomers in DES, thus resulting in higher selectivity of xylan removal. AlCl 3 showed the strongest synergistic effect with DES on accelerating the processes, while FeCl 2 is best one for xylo-oligomers accumulation, affording the highest xylo-oligomers yield of 66.1% for only 10 min. Furthermore, the kinetic study indicates that the 'potential hydrolysis degree' model could well describe the xylan hydrolysis processes and glycolic acid/lactic acid (3:1) is a promising solvent for xylo-oligomers production, in particular, it worked well with FeCl 2 for the excellent accumulation of xylo-oligomers., Conclusions: Glycolic acid-based deep eutectic solvents can be successfully applied in corncob fractionation with excellent xylo-oligomers and fermentable sugars yields on mild conditions, and the large amount of xylo-oligosaccharides accumulation could be achieved by specific process controlling. The strategies established here can be useful for developing high-valued products from biomass., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Rationale: Cardiac fibrosis is an adverse consequence of aberrant fibroblast activation and extracellular matrix (ECM) deposition following myocardial infarction (MI). Recently, long noncoding RNAs (lncRNAs) have been reported to participate in multiple cardiac diseases. However, the biological functions of lncRNA rhabdomyosarcoma 2-associated transcript (RMST) in cardiac fibrosis remain largely unknown. Methods: The role of RMST in regulating cardiac fibroblast (CF) proliferation, fibroblast-to-myofibroblast transition (FMT), and ECM production, which were induced by transforming growth factor-β1, was evaluated through immunofluorescence staining, cell contraction assay, cell migration assay, qRT-PCR, and western blot. The therapeutic effect of RMST silencing was assessed in murine and porcine MI models. Results: The present study showed that RMST expression was upregulated and associated with cardiac fibrosis in murine and porcine MI models. Further loss-of-function studies demonstrated that RMST silencing in vitro significantly inhibited CF proliferation, FMT, and ECM production. Accordingly, RMST knockdown in vivo alleviated cardiac fibrosis and improved cardiac contractile function in MI mice. Moreover, RMST acted as a competitive endogenous RNA of miR-24-3p. miR-24-3p inhibition abolished, while miR-24-3p agomir reproduced, the RMST knockdown-mediated effects on CF fibrosis by regulating the lysyl oxidase signaling pathway. Finally, the therapeutic potential of RMST knockdown was evaluated in a porcine MI model, and local RMST knockdown significantly inhibited cardiac fibrosis and improved myocardial contractile function in pigs after MI. Conclusion: Our findings identified RMST as a crucial regulator of cardiac fibrosis, and targeting RMST may develop a novel and efficient therapeutic strategy for treating fibrosis-related cardiac diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: This study aimed at exploring a new tooth development evaluation method for age assessment and investigating the dynamic alteration and potential trend of tooth development by orthopantomograms (OPGs), in order to provide references for tooth development prediction and forensic purpose., Materials and Methods: A total of 132 OPGs of children aged 3-8 years were collected. The developmental stages of the permanent mandibular second molar (M2)were evaluated by experienced examiners according to the Nolla method and Mimics software, respectively. Quantitative analysis of the ratio of the radiopaque calcified area to the dental follicle (RCA/DF) in different stages, ages, sexes and quadrants were evaluated and compared via descriptive statistics and Spearman's correlation coefficient analysis., Results: There was a strong, positive correlation between the examiners' evaluation and mimics analysis results. With the age increased, the Nolla stage of M2 observed by OPGs increased, and the RCA/DF showed increased trends both in males and females. There were significant differences of the RCA/DF of the M2 at various ages. The tooth calcification development of female was 9.08% earlier than that of male between 3 and 8 years old. However, teeth of male seemed to develop faster than that of female during this period. There was no significant difference between left and right quadrant either according to the Nolla stage or RCA/DF., Conclusions: The RCA/DF value obtained from OPGs of the developmental mandibular second permanent molars could be used as a reliable indicator for tooth maturity and age estimation in children aged 3-8 years., Clinical Relevance: Age assessment based on radiographs is considered as a reliable and efficient indicator for judging different types of malocclusion, making suitable orthodontic treatment plan, deciding the extraction time of retained deciduous teeth in clinic practice., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

HOXC10 has been reported to be upregulated in ovarian cancer (OC) tissues, attributing to the metastasis of OC. However, the specific functions of HOXC10 in OC, especially its role in chemoresistance, remain to be determined. Therefore, in this study, we explored the function and the underlying mechanisms of HOXC10 in carboplatin resistance of OC. A variety of approaches were utilized to analyze the expression of HOXC10 and its related genes. The effect of HOXC10 in cell growth and chemoresistance was investigated in carboplatin-resistant OC subline TOV21G-R and the parental TOV21G-P cells. ROC curve and survival analysis were conducted to determine the predictive value of HOXC10 and ABCC3 combination in carboplatin resistance and the prognosis of OC. Luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay were used to explore the direct regulation of β-catenin by HOXC10. Our results demonstrated that the expression of HOXC10 was upregulated both in the carboplatin-resistant OC tissues and TOV21G-R cells. Furthermore, the upregulation of HOXC10 could promote the expression of ABCC3 by transcriptionally upregulating β-catenin. Moreover, overexpression of HOXC10 could decrease the sensitivity of cells to carboplatin, while knocking down HOXC10 had the opposite effect both in vitro and in vivo . Therefore, the expression of HOXC10/ABCC3 could be a novel biomarker for predicting the carboplatin resistance and the prognosis of OC patients., Competing Interests: None., (AJCR Copyright © 2022.)

An increasing number of chemical technologies to wipe out contaminants within an incredibly short period of time have been developed recently, while their application was always hindered by the inefficient or improper mixing of reactants. To address this issue, the present work proposed a new static mixer named Tai-Chi which consists of blade, fin, and spoiler elements. Tai-Chi mixer can slice and divert the solutions inside and generate high shear flow to promote mixing process. Numerical simulations helped to determine the optimal operating conditions for Tai-Chi mixer, including laying its components anterior to the injection nozzles and keeping the velocity rate ratio of main pipe to branch pipe within the range of 0.5 to 1. Numerical simulations further proved that Tai-Chi mixer could strike a great balance between mixing performance (coefficient of variation [CoV] reaches 0.1 within 5 to 7 pipe diameters downstream) and head loss (nearly a half of other high shear static mixer in the market). Data of pilot-scale testing by Tai-Chi mixer confirm that 80% sulfamethoxazole could be eliminated in permanganate/bisulfite process within 8 pipe diameters, as well as showed the superiority of Tai-Chi's mixing performance in early stage compared with other static mixers in the market. PRACTITIONER POINTS: A Tai-Chi static mixer with blade, fin, and spoiler elements is devised. The optimal condition of flow rate and installment of Tai-Chi mixer is determined. Ultra-fast mixing is achieved by Tai-Chi (CoV < 0.1 within 5-7 pipe diameters). Pilot-scale test verifies the mixing efficiency of Tai-Chi mixer., (© 2022 Water Environment Federation.)

Previous studies in our laboratory have reported that miR-222-3p was a tumor-suppressive miRNA in OC. This study aims to further understand the regulatory role of miR-222-3p in OC and provide a new mechanism for its prevention and treatment. We first found that miR-222-3p inhibited the migration and proliferation of OC cells. Then, we observed CDK19 was highly expressed in OC and inversely correlated with miR-222-3p. Besides, we observed that miR-222-3p directly binds to the 3'-UTR of CDK19 and inhibits CDK19 translation, thus inhibiting OC cell migration and proliferation in vitro and repressed tumor growth in vivo. We also observed the inhibitory effect of Hotair on miR-222-3p in OC. In addition, Hotair could promote the proliferation and migration of OC cells in vitro and facilitate the growth and metastasis of tumors in vivo. Moreover, Hotair was positively correlated with CDK19 expression. These results suggest Hotair indirectly up-regulates CDK19 through sponging miR-222-3p, which enhances the malignant behavior of OC. This provides a further understanding of the mechanism of the occurrence and development of OC., (© 2022. The Author(s).)

In this work, a new method of resonance light scattering was developed for the sensitive and selective detection of butachlor. Firstly, buckwheat was used as the main carbon source to prepare a new type of doped carbon quantum dot using the hydrothermal method. A new method for the determination of butachlor was then established by the change in resonance light scattering intensity after the addition of butachlor into the doped carbon quantum dot solution. The detection effect was successfully optimized by investigating the optimum reaction conditions. Under the optimum conditions, the resonance light scattering intensity of doped carbon quantum dots was greatly enhanced at 460 nm after the addition of butachlor, and the intensity changes were linearly correlated with the butachlor concentration in the range of 1-7 μg L -1 . The detection limit was 0.136 μg L -1 , and the recoveries ranged between 98.6% and 101.8%. This method was also used for butachlor detection in environmental water.

Background: The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal., Results: Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1., Conclusions: L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application., (© 2021. The Author(s).)

Background: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors., Methods: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge., Results: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039)., Conclusions: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required., (© 2021. The Author(s).)

Most of the current approaches to influenza vaccine design focus on antibodies against influenza (HA). However, these influenza vaccines typically provide strain-specific protection against mostly homologous subtypes. There is an urgent need to develop a universal vaccine that confers cross-protection against influenza viruses. Of note, the HA stalk domain (HAsd) is a promising target for such an influenza vaccine. In this study, we generated recombinant Lactococcus lactis ( L. lactis )/pNZ8150-phosphatidylglycerophosphate synthetase A (pgsA)-HAsd, in which pgsA was used as an anchor protein, and investigated the immunogenicity of HAsd in a mouse model by oral administration without the use of a mucosal adjuvant. Compared with L. lactis /pNZ8150-pgsA, mice were orally vaccinated with L. lactis /pNZ8150-pgsA-HAsd and then produced strong humoral and mucosal immune responses. Importantly, L. lactis /pNZ8150-pgsA-HAsd provided cross-protection against H5N1, H3N2 and H1N1 virus infections. Our data support the hypothesis that HAsd presented on the surface of L. lactis can provide cross-protective immunity against divergent influenza A viruses. Taken together, these findings suggest that L. lactis /pNZ8150-pgsA-HAsd can be considered an alternative approach to developing a novel universal vaccine during an influenza A pandemic. Abbreviations: HA, HAsd, HA stalk domain; L. lactis, Lactococcus lactis ; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IFA, immunofluorescence assay; PBS, phosphate-buffered saline; pgsA, phosphatidylglycerophosphate synthetase A; SPF, specific pathogen-free; CFU, colony-forming unit; BSL-3, biosafety level-3 laboratory; TCID 50 , 50% tissue culture infective dose; ELISA, enzyme-linked immunosorbent assay; OD, optical density; LTB, liable enterotoxin B subunit; CTB, cholera toxin B subunit.

Nematode species are well-known for their invariant cell lineage pattern during development. Combining knowledge about the fate specification induced by asymmetric division and the anti-correlation between cell cycle length and cell volume in Caenorhabditis elegans, we propose a minimal model to simulate lineage initiation by altering cell volume segregation ratio in each division, and quantify the derived pattern's performance in proliferation speed, fate diversity, and space robustness. The stereotypic pattern in C. elegans embryo is found to be one of the most optimal solutions taking minimum time to achieve the cell number before gastrulation, by programming asymmetric divisions as a strategy.

Autophagosome-lysosome pathway (ALP) insufficiency has been suggested to play a critical role in the pathogenesis of cardiac hypertrophy. However, the mechanisms underlying ALP insufficiency remain largely unknown, and strategies to specifically manipulate ALP insufficiency for treating cardiac hypertrophy are lacking. Transcription factor EB (TFEB), as a master regulator of ALP, regulates the generation and function of autophagosomes and lysosomes. We found that TFEB was significantly decreased, whereas autophagosome markers were increased in phenylephrine (PE)-induced and transverse aortic constriction-induced cardiomyocyte hypertrophy and failing hearts from patients with dilated cardiomyopathy. Knocking down TFEB induced ALP insufficiency, as indicated by increased autophagosome markers, decreased light chain 3II flux, and cardiomyocyte hypertrophy manifested through increased levels of atrial natriuretic peptide and β-myosin heavy chain and enlarged cell size. The effects of TFEB knockdown were abolished by promoting autophagy. TFEB overexpression improved autophagic flux and attenuated PE-stimulated cardiomyocyte hypertrophy and transverse aortic constriction-induced hypertrophic remodeling, fibrosis, and cardiac dysfunction. Curcumin analog compound C1, a specific TFEB activator, similarly attenuated PE-induced ALP insufficiency and cardiomyocyte hypertrophy. TFEB knockdown increased the accumulation of GATA4, a transcription factor for several genes causing cardiac hypertrophy by blocking autophagic degradation of GATA4, whereas knocking down GATA4 attenuated TFEB downregulation-induced cardiomyocyte hypertrophy. Both TFEB overexpression and C1 promoted GATA4 autophagic degradation and alleviated PE-induced cardiomyocyte hypertrophy. In conclusion, TFEB downregulation plays a vital role in the development of pressure overload-induced cardiac hypertrophy by causing ALP insufficiency and blocking autophagic degradation. Activation of TFEB represents a potential therapeutic strategy for treating cardiac hypertrophy., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

White spot syndrome virus (WSSV) is the major pathogen that leads to severe mortalities in cultured shrimp worldwide. The envelope proteins VP28 and VP24 of WSSV are considered potential vaccine candidate antigens. In this study, we utilized a Saccharomyces cerevisiae (S. cerevisiae) surface display system to demonstrate the feasibility of this platform for developing a vaccine candidate against WSSV. EBY100/pYD1-VP28-VP24 was generated, and the fusion protein VP28-VP24 was present on the surface of S. cerevisiae. Penaeus vannamei (P. vannamei) was used as an animal model. Oral administration of EBY100/pYD1-VP28-VP24 could induce significant activities of immune-related enzymes such as superoxide dismutase (SOD) and phenoloxidase (PO). Importantly, WSSV challenge indicated that oral administration of EBY100/pYD1-VP28-VP24 could confer 100% protection with a corresponding decrease in the viral load. The collective results strongly highlight the potential of a S. cerevisiae-based oral vaccine as an efficient control strategy for combating WSSV infection in shrimp aquaculture., (Copyright © 2021 Elsevier B.V. All rights reserved.)

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor β , epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53 , PTEN and RB , and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance., (© 2021 The Author(s).)

Diesel/natural gas (NG) can effectively improve the performance and reduce emissions of the reactivity-controlled compression ignition (RCCI) engine. In this work, n -hexadecane was used to characterize diesel and the methane/ethane/propane mixture was used to characterize NG, and a simplified diesel/NG mechanism containing 645 reactions and 155 species was established. We used brute force sensitivity analysis to optimize the key dynamic parameters of the mechanism and, through the laminar flame velocity, the substance concentration in the jet-stirred reactors and the ignition delay in the shock tube to verify the optimized n -hexadecane/NG mechanism and found that this mechanism can better respond to diesel/NG. Finally, the mechanism was coupled with the computational fluid dynamic (CFD) to study the effect of different diesel injection timings (DITs) on the combustion performance of RCCI engines. The results show that as the DIT advanced, the temperature distribution in the cylinder became uneven. Also, when the temperature was lower, the content of unburned methane in the cylinder increased. When the DIT was 45° crank angle (CA) before the top dead center (BTDC), the temperature and equivalent in the cylinder were more evenly distributed than in the cylinder and the unburned methane content was lower and diesel/NG exhibited a better combustion effect. The diesel/natural gas mechanism model can be better applied to the CFD simulation of dual-fuel RCCI engines., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Immune checkpoint blocking (ICB) immunotherapy has achieved great success in the treatment of various malignancies. Although not have been approved for the treatment of ovarian cancer (OC), it has been actively tested for the treatment of OC. However, biomarkers that could indicate the immune status of OC and predict the response to ICB are rare. We downloaded RNAseq and clinical data of OC from The Cancer Genome Atlas (TCGA). Data analysis revealed both TMB high and immunity high were significantly related to better survival of OC. Up-regulated differentially expressed genes (Up-DEGs) were identified by analyzing the gene expression levels. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the "GSVA" and "limma" package in R software. The correlation of genes with overall survival was also analyzed by conducted Kaplan-Meier survival analysis. Four genes, CXCL13, FCRLA, MS4A1, and PLA2G2D were found positively correlated with better prognosis of OC and mainly involved in immune response-related pathways. Finally, TIMER and TIDE were used to predict gene immune function and its association with immunotherapy. We found that these four genes were positively correlated with better response to immune checkpoint blockade-based immunotherapy. Altogether, CXCL13, FCRLA, MS4A1, and PLA2G2D may be used as potential therapeutic genes for reflecting OC immune status and predicting response to immunotherapy., 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 © 2021 Fan, Lei, Lin, Zhou, Shu, Yan, Chen, Zhang and Yin.)

Background: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic., Results: We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model., Conclusions: Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.

A safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional administration of a S. cerevisiae-based vaccine (EBY100/pYD1-HA) via injection led to protection against the homologous H5N1 virus in a mouse model. Because the diameter of S. cerevisiae is approximately 10 μm, which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring protection in poultry. We extended our work by evaluating the immunogenicity and protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided protection against challenges with a homologous and a heterologous H5N1 viruses. These findings suggest that EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the limitations of conventional injection routes. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

The arterial mechanical microenvironment, including stiffness, is a crucial pathophysiological feature of vascular remodeling, such as neointimal hyperplasia after carotid endarterectomy and balloon dilatation surgeries. In this study, we examined changes in neointimal stiffness in a Sprague-Dawley rat carotid artery intimal injury model and revealed that extracellular matrix (ECM) secretion and vascular stiffness were increased. Once the endothelial layer is damaged in vivo , activated platelets adhere to the intima and may secrete platelet-derived extracellular vesicles (pEVs) and communicate with vascular smooth muscle cells (VSMCs). In vitro , pEVs stimulated VSMCs to promote collagen secretion and cell adhesion. MRNA sequencing analysis of a carotid artery intimal injury model showed that ECM factors, including col8a1, col8a2, col12a1, and elastin, were upregulated. Subsequently, ingenuity pathway analysis (IPA) was used to examine the possible signaling pathways involved in the formation of ECM, of which the Akt pathway played a central role. In vitro , pEVs activated Akt signaling through the PIP 3 pathway and induced the production of Col8a1. MicroRNA (miR) sequencing of pEVs released from activated platelets revealed that 14 of the top 30 miRs in pEVs targeted PTEN, which could promote the activation of the Akt pathway. Further research showed that the most abundant miR targeting PTEN was miR-92a-3p, which promoted Col8a1 expression. Interestingly, knockdown of Col8a1 expression in vivo abrogated the increase in carotid artery stiffness and simultaneously increased the degree of neointimal hyperplasia. Our results revealed that pEVs may deliver miR-92a-3p to VSMCs to induce the production and secretion of Col8a1 via the PTEN/PIP3/Akt pathway, subsequently increasing vascular stiffness. Therefore, pEVs and key molecules may be potential therapeutic targets for treating neointimal hyperplasia., 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 © 2021 Bao, Li, Xu, Su, Han, Bao, Liu, Fan, Lou, Chen, Jiang, Gong and Qi.)

The Ebbinghaus illusion (EI) is an optical illusion of relative size perception that reflects the contextual integration ability in the visual modality. The current study investigated the genetic basis of two subtypes of EI, EI overestimation, and EI underestimation in humans, using quantitative genomic analyses. A total of 2825 Chinese adults were tested on their magnitudes of EI overestimation and underestimation using the method of adjustment, a standard psychophysical protocol. Heritability estimation based on common single nucleotide polymorphisms (SNPs) revealed a moderate heritability (34.3%) of EI overestimation but a nonsignificant heritability of EI underestimation. A meta-analysis of two phases (phase 1: n = 1986, phase 2: n = 839) of genome-wide association study (GWAS) discovered 1969 and 58 SNPs reaching genome-wide significance for EI overestimation and EI underestimation, respectively. Among these SNPs, 55 linkage-disequilibrium-independent SNPs were associated with EI overestimation in phase 1 with genome-wide significance and their associations could be confirmed in phase 2 cohort. Gene-based analyses found seven genes to be associated with EI overestimation at the genome-wide level, two from meta-analysis, and five from classical two-stage analysis. Overall, this study provided consistent evidence for a substantial genetic basis of the Ebbinghaus illusion.

Introduction: Amelogenin (AMEL) plays critical roles during enamel and dentin matrix deposition and mineralization. Most studies focused on the expression patterns of AMEL through the bud, cap, and bell stages. The spatial-temporal expression of AMEL protein during different mineralization stages, especially from presence of crypts to crown completed stages, remains unknown. Thus, the distribution pattern of AMEL in tooth crown formation from Nolla Stage 1 to 6 was investigated., Methods: Porcine mandibular molar tooth germs from Nolla Stage 1 to 6 were obtained. The dynamic morphologic changes of tooth germs were examined by X-ray and surgical operating microscope. The AMEL protein expression was evaluated immunohistochemically, then analyzed semi-quantitatively, and further visualized via heat map., Results: Tooth germs continuously increased in size from Nolla Stage 1 to 6. AMEL expression in the newly formed enamel kept negative, but presented intensively positive in the previously formed enamel from Stage 1 to 3. The adjacent enamel-dentin junction (EDJ) was strongly positive during the whole process. In predentin, AMEL was weakly seen at Stage 1 and then dramatically up-regulated from Stage 2 to Stage 3, then down-regulated but was still apparently seen in the whole process. AMEL expression in dentin was decreased during dentin matrix secretion and mineralization., Conclusions: This study identified the dynamic distribution of AMEL during porcine tooth crown formation. Semi-quantitative analysis and heat map emerged as reliable indicators in demonstrating AMEL distribution pattern., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R 0 through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R 0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development.

Background: Helicobacter pylori (H. pylori) is a common human pathogenic bacterium that is associated with gastric diseases. The current leading clinical therapy is combination antibiotics, but this treatment has safety issues, especially the induction of drug resistance. Therefore, developing a safe and effective vaccine against H. pylori is one of the best alternatives., Objective: To develop Saccharomyces cerevisiae (S. cerevisiae)-based oral vaccines and then demonstrate the feasibility of this platform for preventing H. pylori infection in the absence of a mucosal adjuvant., Materials and Methods: Saccharomyces cerevisiae (S. cerevisiae)-based oral vaccines, including EBY100/pYD1-UreB and EBY100/pYD1-VacA, were generated and analyzed by Western blot, Immunofluorescence analysis, flow cytometric assay, and indirect enzyme-link immunosorbent assay (ELISA). Further, antibody responses induced by oral administration of EBY100/pYD1-UreB, EBY100/pYD1-VacA, or EBY100/pYD1-UreB + EBY100/pYD1-VacA were measured in a mouse model. Lastly, the vaccinated mice were infected with H. pylori SS1, and colonization in the stomach were evaluated., Results: Saccharomyces cerevisiae-based H. pylori oral vaccines were successfully constructed. Mice orally administered with EBY100/pYD1-UreB, EBY100/pYD1-VacA, or EBY100/pYD1-UreB + EBY100/pYD1-VacA exhibited a significant humoral immune response as well as a mucosal immune response. Importantly, S. cerevisiae-based oral vaccines could effectively reduce bacterial loads with statistical significance after H. pylori infection., Conclusions: Our study shows that S. cerevisiae-based platforms can serve as an alternative approach for the future development of promising bacterial oral vaccine candidates., (© 2020 John Wiley & Sons Ltd.)

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation., Competing Interests: The authors declare no competing interest.

The type II protein arginine methyltransferase 5 (PRMT5) has been engaged in various human cancer development and progression types. Nevertheless, few studies uncover the biological functions of PRMT5 in the epithelial-mesenchymal transition (EMT) of human lung cancer cells, and the associated molecular mechanisms and signaling cascades are entirely unknown. Here, we show that PRMT5 is the ectopic expression in human lung cancer tissues and cell lines. Further study reveals that silencing PRMT5 by lentivirus-mediated shRNA or blocking of PRMT5 by specific inhibitor GSK591 attenuates the expression levels of EMT-related markers in vivo , using the xenograft mouse model. Moreover, our results show that down-regulation of PRMT5 impairs EGFR/Akt signaling cascades in human lung cancer cells, whereas re-expression of PRMT5 recovers those changes, suggesting that PRMT5 regulates EMT probably through EGFR/Akt signaling axis. Altogether, our results demonstrate that PRMT5 serves as a critical oncogenic regulator and promotes EMT in human lung cancer cells. More importantly, our findings also suggest that PRMT5 may be a potential therapeutic candidate for the treatment of human lung cancer.

Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent environmental pollutants. They exert toxic effects at different developmental stages of plants. Plant defense mechanisms against PAHs are poorly understood. To this end, transcriptomics and widely targeted metabolomic sequencing were used to study the changes in gene expression and metabolites that occur in the roots of Salix viminalis subjected to phenanthrene stress. Significant variations in genes and metabolites were observed between treatment groups and the control group. Thirteen amino acids and key genes involved in their biosynthesis were upregulated exposed to phenanthrene. Cysteine biosynthesis was upregulated. Sucrose, inositol galactoside, and mellidiose were the main carbohydrates that were largely accumulated. Glutathione biosynthesis was enhanced in order to scavenge reactive oxygen species and detoxify the phenanthrene. Glucosinolate and flavonoid biosynthesis were upregulated. The production of pinocembrin, apigenin, and epigallocatechin increased, which may play a role in antioxidation to resist phenanthrene stress. In addition, levels of six amino acids and N,N'-(p-coumaroyl)-cinnamoyl-caffeoyl-spermidine were significantly increased, which may have helped protect the plant against phenanthrene stress. These results demonstrated that S. viminalis had a positive defense strategy in response to phenanthrene challenge. Subsequent defense-related reactions may have also occurred within 24 h of phenanthrene exposure. The findings of the present study would be useful in elucidating the molecular mechanisms regulating plant responses to PAH challenges and would help guide crop and plant breeders in enhancing PAH 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 © 2020. Published by Elsevier Ltd.)

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background and Purpose: There are important differences in the treatment and prognosis of adult intracranial low-grade ependymomas (grade II) versus anaplastic ependymomas (grade III). We evaluated the value of the apparent diffusion coefficient (ADC) for differentiating these two tumors and further investigated the relationship between ADC values and the Ki-67 proliferation index., Methods: Clinical and preoperative magnetic resonance imaging data of 35 cases of adult intracranial ependymomas were retrospectively analyzed, including 20 low-grade ependymomas and 15 anaplastic ependymomas. The minimum ADC (ADCmin), average ADC (ADCmean), and normalized ADC (nADC) were compared between the two groups. Receiver operating characteristic curves were drawn to evaluate the differentiating accuracy of ADC values. The Ki-67 proliferation index of the solid tumor components was also measured to explore its relationship with ADC values., Results: The ADCmin (.89 ± .17 vs. .66 ± .09 × 10 -3  mm 2 /second), ADCmean (.98 ± .21 vs. .72 ± .11 × 10 -3 mm 2 /second), and nADC (1.38 ± .31 vs. 1.02 ± .18 × 10 -3  mm 2 /second) were significantly higher in adult intracranial low-grade ependymomas than anaplastic ependymomas cases (all P < .05). ADCmean best distinguished the two groups, with an area under the curve value of .900. Using .716 × 10 -3  mm 2 /second as the optimal threshold, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the two groups were 66.7%, 100%, 85.7%, 100%, and 80%, respectively. ADCmin (r = -.490), ADCmean (r = -.449), and nADC (r = -.425) showed significant negative correlations with the Ki-67 proliferation index (all P < .05)., Conclusions: ADC values can differentiate adult intracranial low-grade ependymomas and anaplastic ependymomas, which could improve the preoperative diagnostic accuracy of these two tumors and guide their treatment., (© 2020 American Society of Neuroimaging.)

Staff and employees "Zero infection" has been achieved during the whole medical activities in the COVID-19 Fangcang Shelter Hospital in Wuhan, China. This study analyses the personnel and environmental protection status of the East-West Lake Fangcang Shelter Hospital. The HCWs were mostly composed of national medical rescue teams, from different provinces in China. Before the COVID-19 outbreak, 82.64% of the HCWs had already known the proper procedure of wearing masks and other personal protective equipment (PPE). For the total of 634 participants entering the inpatient areas, 99.8% of them took occupational protection trainings via various methods. By carefully training and supervision, most of them were competent to work in the inpatient areas six hours/d, three-four times/week. Besides, 7.8% experienced different types of occupational exposure, which mainly caused by the damage of PPE. Once exposed, the HCWs would disinfect skin or mucous in time. No SARS-CoV-2 RNA was detected in 48 air and environmental samples after regular disinfection and cleaning. To conclude, the bundle including intensive training, strengthened personal protection, strict environmental disinfection and timely remedial measures for occupational exposure had ensured the safety of the East-West Lake Fangcang Shelter Hospital.

Mucin 1 (MUC1) is a transmembrane mucin glycoprotein expressed on the surface of almost all epithelial cells. Aberrantly glycosylated MUC1 is associated with cellular transformation from a normal to malignant phenotype in human cancers. Therefore, MUC1 is the major target for the design and development of cancer vaccines. MUC1-based cancer vaccines are a promising strategy for preventing cancer progression and metastasis. This review summarizes the most significant milestones achieved to date in the development of different MUC-1-based vaccine approaches in clinical trials. Further, it provides perspectives for future research that may promote clinical advances in infection-associated cancers., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry. The currently available avian influenza H5N1 vaccines for poultry are clade-specific. Therefore, an effective vaccine for preventing and controlling H5N1 viruses belonging to different clades needs to be developed., Results: Recombinant L. lactis/pNZ8148-Spax-HA was generated, and the influenza virus haemagglutinin (HA) protein of A/Vietnam/1203/2004 (H5N1) was displayed on the surface of Lactococcus lactis (L. lactis). Spax was used as an anchor protein. Chickens vaccinated orally with unadjuvanted L. lactis/pNZ8148-Spax-HA could produce significant humoral and mucosal responses and neutralizing activities against H5N1 viruses belonging to different clades. Importantly, unadjuvanted L. lactis/pNZ8148-Spax-HA conferred cross-clade protection against lethal challenge with different H5N1 viruses in the chicken model., Conclusion: This study provides insights into the cross-clade protection conferred by unadjuvanted L. lactis/pNZ8148-Spax-HA, and the results might help the establishment of a promising platform for the development of a safe and effective H5N1 cross-clade vaccine for poultry.

Background: Chromosome mis-segregation caused by spindle assembly checkpoint (SAC) dysfunction during mitosis is an important pathogenic factor in cancer, and modulating SAC function has emerged as a potential novel therapy for non-small cell lung cancer (NSCLC). UbcH10 is considered to be associated with SAC function and the pathological types and clinical grades of NSCLC. KIAA0101, which contains a highly conserved proliferating cell nuclear antigen (PCNA)-binding motif that is involved in DNA repair in cancer cells, plays an important role in the regulation of SAC function in NSCLC cells, and bioinformatics predictions showed that this regulatory role is related to UbcH10. We hypothesized KIAA0101 and UbcH10 interact to mediate SAC dysfunction and neoplastic transformation during the development of USCLC., Methods: NSCLC cell lines were used to investigate the spatial-temporal correlation between UbcH10 and KIAA0101 expression and the downstream effects of modulating their expression were evaluated. Further immunoprecipitation assays were used to investigate the possible mechanism underlying the correlation between UbcH10 and KIAA0101. Eventually, the effect of modulating UbcH10 and KIAA010 on tumor growth and its possible mechanisms were explored through in vivo tumor-bearing models., Results: In this study, we demonstrated that both UbcH10 and KIAA0101 were upregulated in NSCLC tissues and cells and that their expression levels were correlated in a spatial and temporal manner. Importantly, UbcH10 and KIAA0101 coordinated to mediate the premature degradation of various SAC components to cause further SAC dysfunction and neoplastic proliferation. Moreover, tumor growth in vivo was significantly inhibited by silencing UbcH10 and KIAA0101 expression., Conclusions: KIAA0101 and UbcH10 interact to cause SAC dysfunction, chromosomal instability and malignant proliferation in NSCLC, suggesting that UbcH10 and KIAA0101 are potential therapeutic targets for the treatment of NSCLC by ameliorating SAC function.

N6-methyladenosine (m 6 A) RNA methylation, involved in cancer initiation and progression, is dynamically regulated by the m 6 A RNA methylation regulators. However, the expression of m 6 A RNA methylation regulators in ovarian cancer and their correlation with prognosis remain elusive. Here, we demonstrated that the 18 central m 6 A RNA methylation regulators were expressed differently between ovarian cancer (OC) and normal tissues. By applying consensus clustering, all ovarian cancer patient cases can be divided into three subgroups (cluster1/2/3) based on overall expression levels of all 18 m 6 A RNA methylation regulators. We systematically analyzed the prognostic value of transcription levels of 18 m 6 A RNA methylation regulators in ovarian cancer and found that insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), vir like m 6 A methyltransferase associated (VIRMA), and zinc finger CCCH-type containing 13 (ZC3H13) yield the highest scores for predicting the prognosis of ovarian cancer. Accordingly, we derived a risk signature consisting of transcription levels of these three selected m 6 A RNA methylation regulators as an independent prognostic marker for OC and validated our findings with data derived from a different ovarian cancer cohort. Moreover, by the Gene Set Enrichment Analysis (GSEA), we demonstrated that the three selected regulators were all correlated with pathways in cancer and WNT signaling pathways. In conclusion, m 6 A RNA methylation regulators are vital participants in ovarian cancer pathology; and IGF2BP1, VIRMA, and ZC3H13 mRNA levels are valuable factors for prognosis prediction and treatment strategy development.

A one-pot efficient biocatalytic strategy for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones was developed in a circulating microwave reactor selecting α-chymotrypsin as the promiscuous biocatalyst. In the circulating reaction system, the combination of microwave heating and external cooling could avoid the denaturation and inactivation of enzyme, and greatly improved the radiation power of microwave, thus improving the specific effects of microwave. During the reaction process, the microwave radiation power was automatically adjusted by adjusting the speed of the reaction mixture circulation. When the microwave power was maintained at 110 W, the best results could be obtained with the highest yield of 96% at 55 °C in 50 min, and the reaction had a wide range of substrates. But no obvious product was detected in a tank microwave reactor at 55 °C for 100 min, under this condition, the microwave power was maintained at about 3 W. As a contrast, the reaction only obtained 63% yield in 55 °C oil bath for 96 h., 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 © 2020 Elsevier Inc. All rights reserved.)

In the beginning stage of heart disease, the blockage of blood flow frequently occurs due to the persistent damage and even death of myocardium. Cicatricial tissue developed after the death of myocardium can affect heart function, which ultimately leads to heart failure. In recent years, several studies carried out about the use of stem cells such as embryonic, pluripotent, cardiac and bone marrow-derived stem cells as well as myoblasts to repair injured myocardium. Current studies focus more on finding appropriate measures to enhance cell homing and survival in order to increase paracrine function. Until now, there is no universal delivery route for mesenchymal stem cells (MSCs) for different diseases. In this review, we summarize the advantages and challenges of the systemic and local pathways of MSC delivery. In addition, we also describe some advanced measures of cell delivery to improve the efficiency of transplantation. The combination of cells and therapeutic substances could be the most reliable method, which allows donor cells to deliver sufficient amounts of paracrine factors and provide long-lasting effects. The cardiac support devices or tissue engineering techniques have the potential to facilitate the controlled release of stem cells on local tissue for a sustained period. A novel promising epicardial drug delivery system is highlighted here, which not only provides MSCs with a favorable environment to promote retention but also increases the contact area and a number of cells recruited in the heart muscle., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Microcystic meningioma (MCM) appears similar to atypical meningioma(AM) as per conventional diagnostic imaging. However, considering their different recurrence rate and prognosis, accurate differential diagnosis is essential for determine the appropriate treatment strategy. The aim of the study was to differentiate MCM from AM by diffusion-weighted imaging (DWI), in order to provide the basis for accurate preoperative diagnosis., Methods: The preoperative clinical data, conventional MRI and DWI data of 15 MCM and 30 AM cases were retrospectively analyzed. The average apparent diffusion coefficient (ADC mean ), minimum ADC (ADC min ) and normalized ADC (nADC) between MCM and AM were compared using two sample t-tests. The value of ADC mean , ADC min and nADC in the differential diagnosis of MCM and AM were calculated by the receiver operating curve (ROC) analysis., Results: The ADC mean (1.06 ± 0.10 vs 0.80 ± 0.11 × 10 -3  mm 2 /s; P < 0.001), ADC min (0.99 ± 0.10 vs 0.74 ± 0.12 × 10 -3  mm 2 /s; P < 0.001) and nADC (1.45 ± 0.17 vs 1.07 ± 0.17; P < .0001) were significantly higher in MCM compared to AM. ADC mean of 0.91 × 10 -3  mm 2 /s showed an optimum area under the ROC curve of 0.967 ± 0.022, and distinguished between MCM and AM with 86.67% sensitivity, 100% specificity and 88.89% accuracy. In addition, its positive and negative predictive values were 96.29% and 77.78% respectively., Conclusions: DWI can differentially diagnose MCM and AM, and ADC mean is a potential quantitative tool that can improve preoperative diagnosis of both tumors.

Background : Epithelial ovarian cancer (EOC) is one of the most lethal malignancies in women worldwide. Many studies showed the transcription factor SNAI2-induced Epithelial-Mesenchymal Transition (EMT) through inhibiting E-cadherin (E-cad) expression. Our previous study reported that miR-222-3p was an important tumor-suppressive miRNA for EOC development and dissemination. The present study aimed to acquire a deeper mechanistic understanding of the role of miR-222-3p regulation that might contribute to improving current anti-metastasis strategies in EOC. Methods : A variety of techniques were used to measure mRNA and protein expression levels, including quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, immunohistochemical (IHC) staining, and immunofluorescence (IF). Four different microRNA (miRNA) target prediction databases were used to predict the target genes of miR-222. Luciferase assay was performed to determine the direct binding of miR-222-3p to the untranslated region (3'-UTR) of PDCD10. The biological effects of PDCD10 and miR-222-3p were also investigated in vitro by Transwell and wound healing assays, as well as in vivo by a xenograft mice model. Combining UCSC and JASPAR, as well as ENCODE public databases, we predicted that the transcription factor SNAI2 could affect miR-222-3p expression. Luciferase assay was utilized to examine the validity of putative SNAI2 binding sites for miR-222-3p regulation. Chromatin immunoprecipitation (ChIP) was used to explore the SNAI2's occupancy on the miR-222-3p promoter. Results : We observed the inhibitory effect of SNAI2 on miR-222-3p transcription and confirmed the tumor-suppressive function of miR-222-3p both in EOC cells and tissues. PDCD10 was upregulated and inversely correlated with miR-222-3p, both in vitro and in vivo , which was consistent with the information in bioinformatics databases. Furthermore, We observed direct binding of miR-222-3p to the 3'-UTR of PDCD10 and inhibition of PDCD10 translation, which, in turn, inhibited EOC cell migration in vitro and repressed EOC xenografted tumor metastasis in vivo . We found that genetic overexpression of PDCD10 (OE-PDCD10) increased cancer metastasis by down-regulating E-cad and enhancing Vimentin (VIM) thereby inducing EMT and promoting β -catenin/Wnt-mediated cell migration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Existing methods for preparing influenza vaccines pose the greatest challenge against highly pandemic avian influenza H7N9 outbreak in the poultry and humans. Exploring a new strategy for manufacturing and delivering a safe and effective H7N9 vaccine is needed urgently., Results: An alternative approach is to develop an influenza H7N9 oral vaccine based on yeast display technology in a timely manner. Hemagglutinin (HA) of A/Anhui/1/2013 (AH-H7N9) is used as a model antigen and characterized its expression on the surface of Saccharomyces cerevisiae (S.cerevisiae) EBY 100. Mice administrated orally with S.cerevisiae EBY100/pYD5-HA produced significant titers of IgG antibody as well as significant amounts of cytokines IFN-γ and IL-4. Importantly, S.cerevisiae EBY100/pYD5-HA could provide effective immune protection against homologous A/Anhui/1/2013 (AH-H7N9) virus challenge., Conclusions: Our findings suggest that platform based on yeast surface technology provides an alternative approach to prepare a promising influenza H7N9 oral vaccine candidate that can significantly shorten the preparedness period and result in effective protection against influenza A pandemic.

The early embryogenesis in the nematode Caenorhabditis elegans is well-known for its stereotypic precision of cell arrangements and their lineage relationship. Much research has been focused on how biochemical processes achieve the highly reproducible cell lineage tree. However, the origin of the robustness in the cell arrangements is poorly understood. Here, we set out to provide a mechanistic explanation of how combining mechanical forces with the order and orientation of cell division ensures a robust arrangement of cells. We used a simplified mechanical model to simulate the arrangement of cells in the face of different disturbances. As a result, we revealed three fail-safe principles for cell self-organization in early nematode embryogenesis: ordering, simultaneity, and the division orientation of cell division events. Our work provides insight into the developmental strategy and contributes to the understanding of how robust or variable the cell arrangement can be in developing embryos.