C500 variants conveying complete mucosal immunity against fatal infections of pigs with Salmonella enterica serovar Choleraesuis C78-1 or F18+ Shiga toxin-producing Escherichia coli

Salmonella enterica serovar Choleraesuis (S. Choleraesuis) C500 strain is a live, attenuated vaccine strain that has been used in China for over 40 years to prevent piglet paratyphoid. However, this vaccine is limited by its toxicity and does not offer protection against diseases caused by F18+ Shiga toxin-producing Escherichia coli (STEC), which accounts for substantial economic losses in the swine industry. We recently generated a less toxic derivative of C500 strain with both asd and crp deletion (S. Choleraesuis C520) and assessed its efficacy in mice. In addition, we demonstrate that C520 is also less toxic in pigs and is effective in protecting pigs against S. Choleraesuis when administered orally. To develop a vaccine with a broader range of protection, we prepared a variant of C520 (S. Choleraesuis C522), which expresses rSF, a fusion protein comprised of the fimbriae adhesin domain FedF and the Shiga toxin-producing IIe B domain antigen. For comparison, we also prepared a control vector strain (S. Choleraesuis C521). After oral vaccination of pigs, these strains contributed to persistent colonization of the intestinal mucosa and lymphoid tissues and elicited both cytokine expression and humoral immune responses. Furthermore, oral immunization with C522 elicited both S. Choleraesuis and rSF-specific immunoglobulin G (IgG) and IgA antibodies in the sera and gut mucosa, respectively. To further evaluate the feasibility and efficacy of these strains as mucosal delivery vectors via oral vaccination, we evaluated their protective efficacy against fatal infection with S. Choleraesuis C78-1, as well as the F18+ Shiga toxin-producing Escherichia coli field strain Ee, which elicits acute edema disease. C521 conferred complete protection against fatal infection with C78-1; and C522 conferred complete protection against fatal infection with both C78-1 and Ee. Our results suggest that C520, C521, and C522 are competent to provide complete mucosal immune protection against fatal infection with S. Choleraesuis in swine and that C522 equally qualifies as an oral vaccine vector for protection against F18+ Shiga toxin-producing Escherichia coli

Monitoring response to neoadjuvant therapy for breast cancer in all treatment phases using an ultrasound deep learning model

PurposeThe aim of this study was to investigate the value of a deep learning model (DLM) based on breast tumor ultrasound image segmentation in predicting pathological response to neoadjuvant chemotherapy (NAC) in breast cancer.MethodsThe dataset contains a total of 1393 ultrasound images of 913 patients from Renmin Hospital of Wuhan University, of which 956 ultrasound images of 856 patients were used as the training set, and 437 ultrasound images of 57 patients underwent NAC were used as the test set. A U-Net-based end-to-end DLM was developed for automatically tumor segmentation and area calculation. The predictive abilities of the DLM, manual segmentation model (MSM), and two traditional ultrasound measurement methods (longest axis model [LAM] and dual-axis model [DAM]) for pathological complete response (pCR) were compared using changes in tumor size ratios to develop receiver operating characteristic curves.ResultsThe average intersection over union value of the DLM was 0.856. The early-stage ultrasound-predicted area under curve (AUC) values of pCR were not significantly different from those of the intermediate and late stages (p< 0.05). The AUCs for MSM, DLM, LAM and DAM were 0.840, 0.756, 0.778 and 0.796, respectively. There was no significant difference in AUC values of the predictive ability of the four models.ConclusionUltrasonography was predictive of pCR in the early stages of NAC. DLM have a similar predictive value to conventional ultrasound for pCR, with an add benefit in effectively improving workflow

Early Mechanical and Microstructure Evolution Characteristics of Concrete in Steam Curing Condition

In order to study the effect of steam curing on early mechanical properties of concrete, the strength, dynamic elastic modulus, and microstructure characteristics of concrete under different curing methods were tested. The results show that the early strength growth rate of steam curing concrete is obviously higher than that of standard curing. The strength development of concrete during steam curing can be divided into three stages. Stage I and stage II (0 h-30 h) are critical periods for concrete strength growth. The dynamic elastic modulus of steam-curing concrete is mainly formed in the early stage and shows a linear rapid growth characteristic. The growth rate of the dynamic elastic modulus of concrete under standard curing condition is relatively slow, but in the later curing period (30 h-48 h), the growth rate of dynamic elastic modulus of concrete is significantly higher than that of steam curing concrete. Steam curing can accelerate the production of cement hydration products which rapidly increases the early strength of concrete. Under the standard curing condition, the hydration product structure of concrete is more compact, which is conducive to the growth of dynamic elastic modulus in a later period. This study provides a theoretical reference for the application of steam curing in engineering, which is important to ensure the production efficiency and quality of concrete in engineering

Effects of Forchlorfenuron on the Morphology, Metabolite Accumulation, and Transcriptional Responses of Siraitia grosvenorii Fruit

Siraitia grosvenorii fruit, called luo-han-guo (LHG), have been used as a traditional Chinese medicine (TCM) and dietary supplements for many years. Mogrosides, the main bioactive ingredients in LHG, are commercially available worldwide as a non-sugar-based and noncaloric sweetener. However, the production cannot meet the increasing market demand because of the low content of mogrosides and the small size of LHG. Therefore, some advanced technologies have been applied for improving the quality of LHG. Forchlorfenuron (CPPU), a plant growth regulator, is widely applied to promote plant yield and the secondary metabolite synthesis. Here, the content of nine mogrosides and three intermediates in LHG that were treated with three different concentrations of CPPU were determined by LC-MS/MS and GC-MS, respectively. The total content of mogrosides in LHG treated with CPPU was not enhanced, and the proportion of some main bioactive ingredients, including mogroside V (MV), were decreased relative to that of the control treatment. Morphological and cytological observations showed CPPU could make an early lignification in fruit epidermal cells, and 5 or 25 mg L−1 CPPU could inhibit LHG growth. The expression levels of 24 key genes in the mogroside biosynthesis pathway were measured and revealed that genes downregulated in upstream, and different expressions of SgUGTs would affect the accumulations and proportions of mogrosides in LHG induced by CPPU. This was the first study that applied CPPU individually on LHG, and assessed effects of CPPU on the morphology, the accumulation of metabolites, and expression profiles of 24 structural genes. The CPPU effects on LHG were undesirable, including development inhibition and the decrease of main mogroside content. These will provide guidance for the rational application of CPPU

Bifunctional Ligand Enables Efficient Gold‐Catalyzed Hydroalkenylation of Propargylic Alcohol

Using the previously designed biphenyl-2-ylphosphine ligand, featuring a remote tertiary amino group, the first gold-catalyzed intermolecular hydroalkenylation of alkynes has been developed. Synthetically valuable conjugated dienyl alcohols are formed in moderate to good yields. A range of alkenyltrifluoroborates are allowed as the alkenyl donor, and no erosion of alkene geometry and/or the propargylic configuration are detected. DFT calculations confirm the critical role of the remote basic group in the ligand as a general-base catalyst for promoting this novel gold catalysis with good efficiency

Ligand-Accelerated Gold-Catalyzed Addition of in Situ Generated Hydrazoic Acid to Alkynes under Neat Conditions

The direct addition of in situ generated hydrazoic acid to alkynes is realized without solvent by using a gold catalyst derived from a recently designed remotely functionalized biaryl-2-ylphosphine ligand (i.e., WangPhos). With terminal alkynes, the additions are mostly realized with 0.1 mol% catalyst loadings and at 40 °C. With more challenging internal alkynes devoid of direct EWG substitution, the one-step transformation is realized for the first time with generally high efficiency at ambient temperature

Bioactive Novel Indole Alkaloids and Steroids from Deep Sea-Derived Fungus Aspergillus fumigatus SCSIO 41012

Two new alkaloids, fumigatosides E (1) and F (2), and a new natural product, 3, 7-diketo-cephalosporin P1 (6) along with five known compounds (3–5, 7, 8) were isolated from deep-sea derived fungal Aspergillus fumigatus SCSIO 41012. Their structures were determined by extensive spectroscopic data analysis, including 1D, 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS), and comparison between the calculated and experimental electronic circular dichroism (ECD) spectra. In addition, all compounds were tested for antibacterial and antifungal inhibitory activities. Compound 1 showed significant antifungal activity against Fusarium oxysporum f. sp. momordicae with MIC at 1.56 µg/mL. Compound 4 exhibited significant higher activity against S. aureus (16,339 and 29,213) with MIC values of 1.56 and 0.78 µg/mL, respectively, and compound 2 exhibited significant activity against A. baumanii ATCC 19606 with a MIC value of 6.25 µg/mL

New Sinularianin Sesquiterpenes from Soft Coral Sinularia sp.

Four new sesquiterpenes, sinularianins C–F (3–6), together with known sinularianins A (1) and B (2) were identified from a South China Sea soft coral Sinularia sp. Compounds 1–6 were evaluated for inhibition of NF-κB activation using the cell-based HEK293 NF-κB luciferase reporter gene assay. Compounds 1 and 4 were exhibited a potent effect with inhibitory rates of 41.3% and 43.0% at the concentration of 10 µg/mL, respectively

Synthesis of Crocin I and Crocin II by Multigene Stacking in <i>Nicotiana benthamiana</i>

Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer’s disease. Crocins are mainly biosynthesized in the stigmas of food–medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco