New marketing strategy model of E-commerce enterprises in the era of digital economy.

With the continuous development of technology, traditional marketing methods no longer meet the needs of the main forces of social consumption, and people urgently need more innovative and personalized marketing strategies. E-commerce companies must develop a comprehensive customer-oriented marketing strategy based on big data and multi-channel to achieve their long-term healthy development. This paper first investigated the impact of the digital economy on e-commerce enterprises, focused on the transformation of the digital economy on the marketing model, expounded the development analysis of e-commerce in the digital economy era, and described the development trend of e-commerce marketing in the digital economy era. Then, this paper expounded the current problems faced by e-commerce enterprises, and discussed the lack of integrity, homogeneity, large-scale marketing strategies, and the lack of analysis and application of big data. After that, this paper put forward the marketing strategy of e-commerce enterprises in the digital economy era, and studied it from three aspects, namely, building a reasonable product management structure, marketing strategy based on customized marketing content, and social media marketing strategy based on information sharing. Then this paper proposed to use genetic algorithm to strengthen the marketing strategy of e-commerce enterprises. Finally, based on experiments and surveys, this paper used genetic algorithms to strengthen the construction of e-commerce enterprise marketing strategy in the digital economy, and concluded that the new e-commerce enterprise marketing strategy was 21% more satisfactory than the traditional new e-commerce enterprise marketing strategy. Through comparison, it can see that the integrity of the marketing plan of the new e-commerce enterprise's marketing strategy was 0.33 higher than that of the traditional e-commerce enterprise's marketing strategy, and the integrity of the promotion strategy was 0.34 higher than that of the traditional e-commerce enterprise's marketing strategy. After using the new e-commerce enterprise marketing strategy, the improved management structure was 0.29 higher than that of the traditional monitoring system, and the high quality of products was 0.18 higher than that of the traditional system.

Computer security technology in E-commerce platform business model construction.

The global e-commerce market is expanding rapidly as the big data era advances and the e-commerce industry thrives. This paper aims to discuss the application of computer security technology in constructing an e-commerce platform business model. The research aims to find effective security technology solutions to strengthen the security of e-commerce platforms, protect user information and rights, and enhance the sustainable development of business models. Big Data-assisted E-Commerce Business Model (BD-ECBM) construction is discussed to overcome the e-commerce platform issues and positively impact marketing strategy decision-makers by raising their level of awareness. The business decision-making process is a series of steps that help businesses overcome obstacles by collecting relevant data, analyzing all relevant alternatives, and settling on a course of action. Big data analytics can improve business management with data fusion technology in many ways. The system's framework of the information service layer, the application-level layer, and the client session layer was developed using the Business model paradigm for accounting for e-past, commerce's capabilities of the platform, and an analysis of supply and demand. It can monitor its rivals in near real-time, adjusting prices, offering more attractive deals, and analyzing negative customer comments to see if it can outperform its rivals. The trial results demonstrate the effectiveness of this method of making marketing decisions and formulating a strategy. Hence, the BD-ECBM technique improves customers' overall satisfaction and experience with the brand while raising the latter's profile.

A novel frameshift mutation in SOX10 gene induced Waardenburg syndrome type II.

OBJECTIVE: To explore the molecular etiology of Waardenburg syndrome type II (WS2) in a family from Yunnan province, China. METHODS: A total of 406 genes related to hereditary hearing loss were sequenced using next-generation sequencing. DNA samples were isolated from the peripheral blood DNA of probands. Those pathogenic mutations detected by next-generation sequencing in probands and their parents were validated by Sanger sequencing. The conservatism of variation sites in genes was also analyzed. The protein expression was detected by flow cytometry. RESULTS: A heterozygous mutation c.178delG (p.D60fs*49) in the SOX10 gene was identified in the proband, which is a frameshift mutation and may cause protein loss of function and considered to be a pathogenic mutation. This was determined to be a de novo mutation because her family were demonstrated to be wild-type and symptom free. SOX10, FGFR3, SOX2, and PAX3 protein levels were reduced as determined by flow cytometry. CONCLUSION: A novel frameshift mutation in SOX10 gene was identified in this study, which may be the cause of WS2 in proband. In addition, FGFR3, SOX2, and PAX3 might also participate in promoting the progression of WS2.

Effect of jujube pulp on acid- and rennet-induced coagulation properties of milk.

Milk coagulation is an important step in the production of fermented dairy products such as yogurt and cheese. Jujube is gaining popularity and acceptance as a food ingredient. In China, jujube yogurt is popular among consumers. However, there is limited information on the effect of jujube on acid- and rennet-induced coagulation properties of milk. The objective of this study was to evaluate the effects of jujube pulp at different concentrations on acid- and rennet-induced coagulation kinetics of milk, and the microstructure of acid- and rennet-induced gels. During acid-induced coagulation, with increasing jujube pulp concentration, the initial pH value decreased; however, the final pH value increased. The initial elasticity index (EI) value increased, and the time point at which the mean square displacement curves lost the linear trend advanced. The sample with 10% jujube pulp had the densest structure and highest EI value. During rennet-induced coagulation, with increasing jujube pulp concentration, the production rate and amount of caseinomacropeptide decreased, and the final EI value increased. Protein aggregates in rennet-induced gels became rough, and the sample with 20% jujube pulp had the highest EI value. This study provides a new perspective and understanding of the application of jujube in fermented dairy products.

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases.

Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.

Magnetic covalent organic frameworks for extraction and determination of endocrine-disrupting chemicals in beverage and water samples.

BACKGROUND: Phenolic endocrine-disrupting chemicals (EDCs) are widespread and easily ingested through the food chain. They pose a serious threat to human health. Magnetic solid-phase extraction (MSPE) is an effective sample pre-treatment technology to determine traces of phenolic EDCs. RESULTS: Magnetic covalent organic framework (COF) (Fe3 O4 @COF) nanospheres were prepared and characterized. The efficient and selective extraction of phenolic EDCs relies on a large specific surface and the inherent porosity of COFs and hydrogen bonding, π-π, and hydrophobic interactions between COF shells and phenolic EDCs. Under optimal conditions, the proposed magnetic solid-phase extraction-high-performance liquid chromatography-ultra violet (MSPE-HPLC-UV) based on the metallic covalent organic framework method for phenolic EDCs shows good linearities (0.002-6 µg mL-1 ), with R2 of 0.995 or higher, and low limits of detection (6-1.200 ng mL-1 ). CONCLUSION: Magnetic covalent organic frameworks (Fe3 O4 @COFs) with good MSPE performance for phenolic EDCs were synthesized by the solvothermal method. The magnetic covalent organic framework-based MSPE-HPLC-UV method was applied successfully to determine phenolic EDCs in beverage and water samples with satisfactory recoveries (90.200%-123%) and relative standard deviations (2.100%-12.100%). © 2023 Society of Chemical Industry.

A novel N-heterocycles substituted oseltamivir derivatives as potent inhibitors of influenza virus neuraminidase: discovery, synthesis and biological evaluation.

Our previous studies have shown that the introduction of structurally diverse benzyl side chains at the C5-NH2 position of oseltamivir to occupy 150-cavity contributes to the binding affinity with neuraminidase and anti-influenza activity. To obtain broad-spectrum neuraminidase inhibitors, we designed and synthesised a series of novel oseltamivir derivatives bearing different N-heterocycles substituents that have been proved to induce opening of the 150-loop of group-2 neuraminidases. Among them, compound 6k bearing 4-((r)-2-methylpyrrolidin-1-yl) benzyl group exhibited antiviral activities similar to or weaker than those of oseltamivir carboxylate against H1N1, H3N2, H5N1, H5N6 and H5N1-H274Y mutant neuraminidases. More encouragingly, 6k displayed nearly 3-fold activity enhancement against H3N2 virus over oseltamivir carboxylate and 2-fold activity enhancement over zanamivir. Molecular docking studies provided insights into the explanation of its broad-spectrum potency against wild-type neuraminidases. Overall, as a promising lead compound, 6k deserves further optimisation by fully considering the ligand induced flexibility of the 150-loop.

Evaluating imputation methods for single-cell RNA-seq data.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) enables the high-throughput profiling of gene expression at the single-cell level. However, overwhelming dropouts within data may obscure meaningful biological signals. Various imputation methods have recently been developed to address this problem. Therefore, it is important to perform a systematic evaluation of different imputation algorithms. RESULTS: In this study, we evaluated 11 of the most recent imputation methods on 12 real biological datasets from immunological studies and 4 simulated datasets. The performance of these methods was compared, based on numerical recovery, cell clustering and marker gene analysis. Most of the methods brought some benefits on numerical recovery. To some extent, the performance of imputation methods varied among protocols. In the cell clustering analysis, no method performed consistently well across all datasets. Some methods performed poorly on real datasets but excellent on simulated datasets. Surprisingly and importantly, some methods had a negative effect on cell clustering. In marker gene analysis, some methods identified potentially novel cell subsets. However, not all of the marker genes were successfully imputed in gene expression, suggesting that imputation challenges remain. CONCLUSIONS: In summary, different imputation methods showed different effects on different datasets, suggesting that imputation may have dataset specificity. Our study reveals the benefits and limitations of various imputation methods and provides a data-driven guidance for scRNA-seq data analysis.

Discovery of N-substituted oseltamivir derivatives as novel neuraminidase inhibitors with improved drug resistance profiles and favorable drug-like properties.

To yield potent neuraminidase inhibitors with improved drug resistance and favorable drug-like properties, two series of novel oseltamivir derivatives targeting the 150-cavity of neuraminidase were designed, synthesized, and biologically evaluated. Among the synthesized compounds, the most potent compound 43b bearing 3-floro-4-cyclopentenylphenzyl moiety exhibited weaker or slightly improved inhibitory activity against wild-type neuraminidases (NAs) of H1N1, H5N1, and H5N8 compared to oseltamivir carboxylate (OSC). Encouragingly, 43b displayed 62.70- and 5.03-fold more potent activity than OSC against mutant NAs of H5N1-H274Y and H1N1-H274Y, respectively. In cellular antiviral assays, 43b exerted equivalent or more potent activities against H1N1, H5N1, and H5N8 compared to OSC with no significant cytotoxicity up to 200 µM. Notably, 43b displayed potent antiviral efficacy in the embryonated egg model, in which achieved a protective effect against H5N1 and H5N8 similar to OSC. Molecular docking studies were implemented to reveal the binding mode of 43b in the binding pocket. Moreover, 43b possessed improved physicochemical properties and ADMET properties compared to OSC by in silico prediction. Taken together, 43b appeared to be a promising lead compound for further investigation.

An exploration of gastric cancer with heterogeneous mismatch repair status.

Survival benefits or symptom alleviation from immune checkpoint blockade therapy can be seen in microsatellite instability-high (MSI-H) cases. However, genetic heterogeneity within a specific subgroup of MSI-H tumors may be associated with poor response and prognosis. We investigated the molecular changes and microsatellite status of the cases with heterogeneous MMR protein staining by polymerase chain reaction (PCR) and next-generation sequencing (NGS). Data from 3723 patients with gastric cancer were retrospectively analyzed to determine the mismatch repair (MMR) status by performing immunohistochemical staining of four major MMR proteins (MLH1, PMS2, MSH2, and MSH6). When heterogeneous MMR protein staining result was positive, PCR and NGS were performed. Heterogeneous MMR protein staining was observed in 12 cases. In microsatellite stable (MSS) cases, TP53 mutation appeared to accompany heterogeneous staining (HS) of MLH1. However, TP53 variation was not observed with MSI-H occurrence. Cases showing heterogeneous MSH6 protein staining revealed MSH6 mutations. Some cases with the same MMR protein staining set had varying MSI results. In one case whose primary and metastatic foci presented MLH1-HS and PMS2-HS, the microsatellite status was classified as MSS and MSI-H, respectively. Moreover, HS was also found in multiple biopsies and surgical specimens. This study found a preliminary relationship between heterogeneously stained MSH6 or MLH1 proteins and their gene mutations, as well as between MSI-H/TP53 - and MSS/TP53 + tumors. The microsatellite status of patients with heterogeneous MMR protein staining is unpredictable. Given the heterogeneity of mismatch repair, microsatellite status should be assessed for all specimens if sufficient specimens can be obtained.

Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel.

BACKGROUND: At present, the hereditary hearing loss homepage, ( https://hereditaryhearingloss.org/ ), includes 258 deafness genes and more than 500 genes that have been reported to cause deafness. With few exceptions, the region-specific distributions are unclear for many of the identified variants and genes. METHODS: Here, we used a custom capture panel to perform targeted sequencing of 518 genes in a cohort of 879 deaf Chinese probands who lived in Yunnan. Mutation sites of the parents were performed by high-throughput sequencing and validated by Sanger sequencing. RESULTS: The ratio of male to female patients was close to 1:1 (441:438) and the age of onset was mainly under six. Most patients (93.5%) were diagnosed with moderate to severe deafness. Four hundred and twenty-eight patients had variants in a deafness gene, with a detection rate of 48.7%. Pathogenic variants were detected in 98 genes and a number of these were recurrent within the cohort. However, many of the variants were rarely observed in the cohort. In accordance with the American College of Medical Genetics and Genomics, pathogenic, likely pathogenic and variants of uncertain significance accounted for 34.3%, 19.3% and 46.4% of all detected variants, respectively. The most common genes included GJB2, SLC26A4, MYO15A, MYO7A, TMC1, CDH23, USH2A and WFS1, which contained variants in more than ten cases. The two genes with the highest mutation frequency were GJB2 and SLC26A4, which accounted for 28.5% (122/428) of positive patients. We showed that more than 60.3% of coding variants were rare and novel. Of the variants that we detected, 80.0% were in coding regions, 17.9% were in introns and 2.1% were copy number variants. CONCLUSION: The common mutation genes and loci detected in this study were different from those detected in other regions or ethnic groups, which suggested that genetic screening or testing programs for deafness should be formulated in accordance with the genetic characteristics of the region.

[Clinical characteristics of 91 patients of otorhinolaryngology head and neck malignant tumors in children].

Objective:To analyze the clinical characteristics, treatment and prognosis of the otolaryngology head and neck malignant tumors in children, in order to improve the diagnosis and treatment of the diseases. Methods:The patients of otorhinolaryngology head and neck malignant solid tumors under 14 years old hospitalized in Kunming Children's Hospital and the First Affiliated Hospital of Kunming Medical University from 2014 to 2020 were retrospectively analyzed. All cases were statistically analyzed according to gender, age, location, pathological type and treatment method. Results:The main clinical manifestations of 91 children were mainly facial and neck masses, including nasal congestion, swallowing discomfort, and continuous intermittent fever. CT and MRI examination showed that the diameter of the tumor was 1.2 cm ×2.0 cm to 5.0 cm×12.0 cm, with a mean of 2.8 cm×3.2 cm, and 19 cases had distant metastasis. The main tissue sources were soft tissue （56 cases） and epithelial tissue （35 cases）. There were 6 pathological types, the most common was sarcoma （41 cases）, followed by neuroblastoma （15 cases）, papillary carcinoma （14 cases）, squamous cell carcinoma （10 cases）, mucoepidermoid carcinoma （8 cases）, and adenocarcinoma （3 cases）. According to the classification of tissue origin, the statistical analysis of gender and pathological type showed statistically significant differences in both gender and pathological types（P<0.01）. Conclusion:The age of onset, primary site, tissue origin and pathological type of otolaryngology head and neck malignancy in children have their own characteristics, which should be comprehensively evaluated and treated with multidisciplinary treatment.

Loss of Human Epidermal Receptor 2 Expression in Formalin-Fixed Paraffin-Embedded Breast Cancer Samples and the Rescuing Effect of Enhanced Antigen Retrieval and Signal Amplification.

As an important therapeutic target in breast cancer, HER2 expression assessed by immunohistochemistry plays a critical role in breast cancer treatment. Recent advances in HER2 antibody-drug conjugate therapy have enabled patients with HER2-low expression breast cancer to benefit from the drugs. However, it is not known whether the HER2-low expression in breast cancer FFPE blocks would be lost as storage time increased. In this study, we aimed to assess the loss of HER2 antigenicity in stored FFPE blocks of breast cancer and the rescue effect of modifying the protocol of antigen staining. We selected archived HER2-low breast cancer FFPE blocks with stored time ranging from 1 year to over 15 years and re-detected the expression of HER2. Our study showed that HER2 antigenicity loss increased with storage time and could cause false negativity in HER2-low detection. Moreover, we showed that by either increasing the antigen retrieval time or applying the tyramide signal amplification (TSA) kit, the HER2 signal can be rescued and detected in about half of the cases with HER2-low loss without causing false positivity.

Discovery of Novel Boron-Containing N-Substituted Oseltamivir Derivatives as Anti-Influenza A Virus Agents for Overcoming N1-H274Y Oseltamivir-Resistant.

To address drug resistance to influenza virus neuraminidase inhibitors (NAIs), a series of novel boron-containing N-substituted oseltamivir derivatives were designed and synthesized to target the 150-cavity of neuraminidase (NA). In NA inhibitory assays, it was found that most of the new compounds exhibited moderate inhibitory potency against the wild-type NAs. Among them, compound 2c bearing 4-(3-boronic acid benzyloxy)benzyl group displayed weaker or slightly improved activities against group-1 NAs (H1N1, H5N1, H5N8 and H5N1-H274Y) compared to that of oseltamivir carboxylate (OSC). Encouragingly, 2c showed 4.6 times greater activity than OSC toward H5N1-H274Y NA. Moreover, 2c exerted equivalent or more potent antiviral activities than OSC against H1N1, H5N1 and H5N8. Additionally, 2c demonstrated low cytotoxicity in vitro and no acute toxicity at the dose of 1000 mg/kg in mice. Molecular docking of 2c was employed to provide a possible explanation for the improved anti-H274Y NA activity, which may be due to the formation of key additional hydrogen bonds with surrounding amino acid residues, such as Arg152, Gln136 and Val149. Taken together, 2c appeared to be a promising lead compound for further optimization.

Case report: Identification and clinical phenotypic analysis of novel mutation of the PPP1CB gene in NSLH2 syndrome.

Objective: To screen and analyze the genetic mutations in the PPP1CB gene in a patient with Noonan syndrome with loose anagen hair-2 (NSLH2) in Yunnan Province, China and explore the possible molecular pathogenesis. Methods: After obtaining informed consent, we collected the patient's medical history and carried out physical and laboratory examinations for the NSLH2 proband and the family members. Genomic DNA was extracted from the peripheral blood of all individuals. The coding regions including all pathogenic exons, parts of introns, and promoters of genes were sequenced by next-generation sequencing. Pathogenic mutations, which were detected in the probands and their parents, were verified by Sanger sequencing. Results: The clinical manifestations of NSLH2 included prominent forehead, yellowish hair, slightly wide eye distance, sparse eyebrows, bilateral auricle deformity, reduced muscle tension, and cardiac and visual abnormalities. The proband carried a c.371A>G mutation in exon 3 of PPP1CB, which is a missense mutation. This was a de novo mutation as the parents of the proband showed no mutation at this site. Conclusion: In this study, we identified a novel mutation of PPP1CB, which enriched the mutation spectrum of the PPP1CB gene and provided a basis for the diagnosis of NSLH2.

Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population.

Immunotherapy shows prospects in treating advanced medullary thyroid carcinoma although controversial reports are present. Recently, histological grading has been applied to medullary thyroid carcinoma by the Ki-67 index, mitotic figures, and tumor necrosis. However, the interrelation of PD-L1 expression, the Ki-67 index, and major genetic alterations of sporadic medullary thyroid carcinoma has not been fully reported. We examined the expression of PD-L1 (SP142 and 22C3) and the Ki-67 index immunohistologically and detected the major genetic alterations by next-generation sequencing in a cohort of sporadic medullary thyroid carcinomas, studied their survival impact, and discussed their interrelation. We identified that a high Ki-67 index (> 2%) and positive RET M918T mutation were correlated with poor disease-free survival but were not correlated with PD-L1 expression. All PD-L1 positive tumors were RET M918T mutation negative, and PD-L1 expression was positively correlated with HRAS mutation. The Ki-67 index was correlated with neither PD-L1 expression nor major genetic alterations. Our results indicate that immunotherapy targeting PD-L1/PD-1 might be more effective for patients with sporadic medullary thyroid carcinoma harboring HRAS mutations.

Correlation between pathological features and protein expressions of TfR1, VEGF and MMP-9 in patients with osteosarcoma.

OBJECTIVE: To analyze the pathological features of patients with osteosarcoma and the correlation of expressions of transferrin receptor 1 (TfR1), vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 in tumor tissue with the pathological features. METHODS: The tumor tissue and paracancerous tissue samples from 31 patients with osteosarcoma were collected before treatment to measure the expressions of TfR1, VEGF and MMP-9. Kaplan-meier curve was used to analyze the relationship of TfR1, VEGF and MMP-9 with the survival time of patients. Log-rank test was used to test the difference, and Spearman test was used to test the correlation. RESULTS: Among the 31 osteosarcoma samples, 23 (74.19%), 24 (77.42%) and 17 (54.84%) samples showed medium-high expressions of VEGF, TfR1 and MMP-9, respectively, which were significantly higher than those in the paracancerous samples (P<0.05). Furthemore, the medium-high expression rates of VEGF, TfR1 and MMP-9 were significantly different in patients with different Enneking stages, different histological differentiation degrees, and with or without distant metastasis. Besides, the expression of VEGF was also significantly different in different-size osteosarcoma samples (P<0.05). The survival time of patients with low expressions of TfR1, VEGF and MMP-9 was significantly longer than that of patients with medium-high expressions (P<0.05). Additionally, in osteosarcoma samples, significant positive correlations were shown between the expressions of TfR1 and VEGF, as well as between TfR1 and MMP-9 (P<0.05), but there was no significant correlation between VEGF and MMP-9 (P>0.05). CONCLUSION: TfR1, VEGF and MMP-9 are abnormally expressed in osteosarcoma lesions, suggesting that they all play a role in the occurrence and development of osteosarcoma.

Iterative Optimization and Structure-Activity Relationship Studies of Oseltamivir Amino Derivatives as Potent and Selective Neuraminidase Inhibitors via Targeting 150-Cavity.

With our continuous endeavors in seeking neuraminidase (NA) inhibitors, we reported herein three series of novel oseltamivir amino derivatives with the goal of exploring the druggable chemical space inside the 150-cavity of influenza virus NAs. Among them, around half of the compounds in series C were demonstrated to be better inhibitors against both wild-type and oseltamivir-resistant group-1 NAs than oseltamivir carboxylate (OSC). Notably, compounds 12d, 12e, 15e, and 15i showed more potent or equipotent antiviral activity against H1N1, H5N1, and H5N8 viruses compared to OSC in cellular assays. Furthermore, compounds 12e and 15e exhibited high metabolic stability in human liver microsomes (HLMs) and low inhibitory effect on main cytochrome P450 (CYP) enzymes, as well as low acute/subacute toxicity and certain antiviral efficacy in vivo. Also, pharmacokinetic (PK) and molecular docking studies were performed. Overall, 12e and 15e possess great potential to serve as anti-influenza candidates and are worthy of further investigation.

Porcine Epidemic Diarrhea Virus Infection Subverts Arsenite-Induced Stress Granules Formation.

Stress granules (SGs) are dynamic cytoplasmic protein-RNA structures that form in response to various stress conditions, including viral infection. Porcine epidemic diarrhea virus (PEDV) variant-related diarrhea has caused devastating economic losses to the swine industry worldwide. In this study, we found that the percentage of PEDV-infected cells containing SGs is nearly 20%; meanwhile, PEDV-infected cells were resistant to sodium arsenite (SA)-induced SGs formation, as demonstrated by the recruitment of SGs marker proteins, including G3BP1 and TIA1. Moreover, the formation of SGs induced by SA treatment was suppressed by PEDV papain-like protease confirmed by confocal microscopy. Further study showed that PEDV infection disrupted SGs formation by downregulating G3BP1 expression. Additionally, PEDV replication was significantly enhanced when SGs' assembly was impaired by silencing G3BP1. Taken together, our findings attempt to illuminate the specific interaction mechanism between SGs and PEDV, which will help us to elucidate the pathogenesis of PEDV infection in the near future.

Effect of Roasting on the Conformational Structure and IgE Binding of Sesame Allergens.

Sesame can trigger a systemic allergic reaction. In the present study, we investigated the responses of the structure and IgE binding of sesame allergens to different roasting treatments (120, 150, and 180 °C for 5 to 30 min). We analyzed the tryptic digestion peptides using a label-free mass spectrometry method. The total amount of soluble proteins in sesame was significantly reduced by roasting at 180 °C, followed by 150 °C. Ses i 1 was the most stable protein during processing as it still possessed a higher protein abundance compared to other allergens after roasting under 180 °C. The most unstable allergens were Ses i 4 and Ses i 7, which suffered severe protein degradation at 180 °C. Roasting at 180 °C remarkably increased the secondary structure content of α-helices but decreased that of ß-sheets, whereas roasting at 120 and 150 °C had a limited effect on the secondary structure of sesame proteins. Moreover, serum pool Western blot analysis showed that the main allergens were oleosin of Ses i 4 and Ses i 5. The IgE-binding ability of sesame allergens was significantly decreased under 180 °C roasting, as well as the solubility of sesame proteins, which showed remarkable congruence in changes. Relative quantification results indicate that individual sesame allergens respond differently to the roasting process. In general, sesame allergens are unstable under roasting treatment. Therefore, the allergenic potential of sesame allergens may be minimized by selecting appropriate parameters during processing.