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HongXiang Gao,1 Xuan He,1 JianFei Du,1 SanHu Yang,2 Yang Wang,1 JunWei Zhang,1 ChenNian Zhao1 1Department of Oncology, Chang’An Hospital, Xi’an, Shaanxi, China; 2Department of Thoracic Surgery, Tangdu Hospital, Xi’an, Shaanxi, China Purpose: To analyze the prognostic factors of primary tracheal carcinoma. Patients and methods: All patients of primary tracheal carcinoma were extracted from the Surveillance, Epidemiology, and End Results database during 1973–2015. The potential prognostic factors were analyzed by using the competing risk analysis of R statistical software. Results: A total of 485 eligible patients were enrolled. The univariate analysis indicated that age, sex, diagnostic confirmation, extension, lymph node, metastasis, multiple primary tumors, primary site surgery, and lymph node dissection were statistically significant for the patients’ death due to tracheal tumor. The multivariate analysis indicated that age (P=0.0000, CI: 1.0255–1.0630), lymph node (P=0.0000, CI: 1.6031–3.4890), metastasis (P=0.0100, CI: 1.1342–2.5790), multiple primary tumors (P=0.0000, CI: 0.0276–0.1090), and primary site surgery (P=0.0001, CI: 0.3565–0.7110) were independent prognostic factors affecting survival, and there were significant differences in the stratification of each prognostic factors. Conclusion: Age, lymph node, metastasis, multiple primary tumors, and primary site surgery were independent prognostic factors of primary tracheal carcinoma. Keywords: primary tracheal carcinoma, SEER, prognostic factor, competing risk analysis

The low solubility of phenolic compounds in oils limits their protective effect on oil quality. In the present study, novel microemulsions were designed and prepared with Ligustrum robustum (Rxob.) Blume polyphenols extract (LRE) using soybean oil as the oil phase, a combination of Tween80 and Span80 as surfactants, and ethanol as the co-surfactant, and subsequently characterized and evaluated their properties and performance in oil. Results showed that the amount of LRE dissolved in prepared microemulsions could reach 0.025 g/g oil. According to the droplet size, rheology, differential scanning calorimetry, and transmission electron microscopy measurements, LRE had no negative effects on microemulsion structure and increased the particle size, viscosity, and interfacial strength of microemulsion. Moreover, LRE exhibited remarkable antioxidant activities, and the LRE-loaded microemulsions showed no obvious cytotoxicity on Caco-2 cells. Furthermore, the LRE-loaded microemulsions exhibited superior effectiveness in inhibiting oil oxidation during storage, compared to the direct addition of LRE. All results suggest that the microemulsion has the potential used as an embedded material for natural antioxidants in food industry., 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 © 2025 Elsevier Ltd. All rights reserved.)

Background: To analyze the epidemiological characteristics of the SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in Healthcare workers (HCWs)., Methods: We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions., Results: Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs 60.1%), cough (78.8% vs 58.0%), and sore throat (75.4% vs 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms, with a higher prevalence among female HCWs., Conclusions: HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Strengthen infection prevention and control is crucial to mitigating infection risk and improving health services., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A novel core-shell structured alginate-based hydrogel bead modified by co-gelatinizing with starch and protocatechuic acid (PA), was designed to modulate physical properties of beads, release behavior and antioxidant stability of encapsulated bioactives. Core was fabricated by ionotropic gelation, and its formulation (ratio of sodium alginate/starch) was determined by particle size/starch distribution, texture and bioactive encapsulation capacity of core. Then, coating core with shell-forming solution co-gelatinized with different doses of PA, and subsequently cross-linked with Ca 2+ to obtain core-shell structured beads. Surface microstructure, mechanical characteristics, and swelling ratio of beads were affected by concentrations of PA. Besides, core-shell structure containing PA could enhance delivery and sustained release of encapsulated phenolic bioactives during in vitro digestion, and improve their antioxidant potential stability. Furthermore, interaction between PA and polysaccharide components was elucidated by FTIR and TGA. The present information was beneficial for the advancement of functional food materials and bioactive delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% (20/23) in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×10 6 /L and was 12 (0, 25)×10 6 /L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Objective: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants., Methods: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals., Results: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination., Conclusions: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study discusses interaction differences between three phenols (protocatechuic acid, naringin and tannic acid) and starch helix, investigates influences of phenols at different doses on properties of maize starch, and further determines their effects on quality and function of maize-starchy foods. Simulated results indicate variations of phenolic structure (phenolic hydroxyl group amount, glycoside structure and steric hindrance) and dose induce phenols form different complexes with starch helix. Formation of different starch-phenols complexes alters gelatinization (1.65-5.63 J/g), pasting form, water binding capacity (8.83-12.69 g/g) and particle size distribution of starch. Meanwhile, differences in starch-phenols complexes are reflected in fingerprint area (R 1045/1022 : 0.920 to 1.047), crystallinity (8.3% to 17.0%), rheology and gel structure of starch. Additionally, phenols change texture and color of cold maize cake, giving them different antioxidant capacity and lower digestibility. Findings are beneficial for understanding interaction between starch and different phenols and their potential application., Competing Interests: Declaration of competing interest We declare that there is no conflict of interests in the submission of this manuscript, and all the authors listed have approved its publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Numerous studies have reported the potential involvement of ferroptosis in the development of atherosclerosis (AS). Acyl-CoA synthetase long chain family member 4 (ACSL4) is an essential component in the promotion of ferroptosis. The present study aimed to investigate the role of ACSL4 and zinc finger translocation-associated protein (ZFTA) in the regulation of endothelial cell ferroptosis in AS. Human umbilical vein endothelial cells (HUVECs) with ACSL4 knockout were generated using CRISPR/Cas9 technology. To assess ferroptosis, malondialdehyde concentration, iron content and reactive oxygen species levels were quantified in the present study. In addition, western blot analysis was conducted to explore the potential mechanisms underlying ACSL4 and ZFTA in the modulation of ferroptosis in HUVECs. The results of the present study demonstrated that the expression levels of ACSL4 and ZFTA were significantly increased in human atherosclerotic plaques. In addition, ACSL4 knockout led to a reduced susceptibility to ferroptosis, while ZFTA contributed to ferroptosis in HUVECs. Results of the present study also demonstrated that ZFTA overexpression upregulated ACSL4 expression in HUVECs, whereas ZFTA knockdown led to decreased ACSL4 expression. Co-transfection experiments demonstrated that the ZTFA overexpression-mediated increase in ferroptosis was reversed following ACSL4 knockdown. Collectively, results of the present study highlighted that ACSL4 mediated the effects of ZFTA on the ferroptosis of HUVECs. Thus, the present study demonstrated the potential role of ACSL4 and ZFTA in the regulation of ferroptosis, and highlighted that ferroptosis-related pathways may act as potential targets in the treatment of AS., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Gao et al.)

The increasing concerns about health have led to a growing demand for high-quality fried foods. The potential uses of Ligustrum robustum (Rxob.) Blume, a traditional tea in China, as natural additives to enhance the quality of starchy food during frying was studied. Results indicated that L. robustum polyphenols extract (LREs) could improve the quality of fried starchy food, according to the tests of color, moisture content, oil content, texture property, and volatile flavor. The in vitro digestion results demonstrated that LRE reduced the final glucose content from 11.35 ± 0.17 to 10.80 ± 0.70 mmol/L and increased the phenolic content of fried starch foods from 1.23 ± 0.04 to 3.76 ± 0.14 mg/g. The appearance and polarizing microscopy results showed that LRE promoted large starch bulges on the surface of fried starchy foods. Meanwhile, X-ray diffraction results showed that LRE increased the intensity of characteristic diffraction peak of fried starch with a range of 21.8%-28%, and Fourier transform infrared results showed that LRE reduced the damage to short-range order structure of starch caused by the frying process. In addition, LRE increased the aggregation of starch granules according to the SEM observation and decreased the enthalpy of starch gelatinization based on the differential scanning calorimetry results. The present results suggest that LREs have the potential to be utilized as a natural additive for regulating the quality of fried starchy food in food industries. PRACTICAL APPLICATION: The enhancement of L. robustum polyphenols on the quality of starchy food during frying was found, and its mechanisms were also explored. This work indicated that L. robustum might be used as a novel economic natural additive for producing high-quality fried foods., (© 2024 Institute of Food Technologists.)

Effects of Epiphyllum oxypetalum (DC.) Haw polysaccharide (EP) on physicochemical/digestive properties of tapioca starch (TS) were investigated, and its effects on final quality of TS-based foods were further determined. Results showed EP significantly decreased gelatinization enthalpy (3.92 to 2.11 J/g) and increased breakdown (302 to 382 cp), thereby inducing the gelatinization of TS. Meanwhile, EP decreased setback viscosity (324 to 258 cp), suggesting the retrogradation of TS paste was inhibited. Rheological determination results suggested EP had an impact on the viscoelasticity of TS paste. Moreover, particle size distribution showed EP increased size of TS by cross-linking. Additionally, the suitable addition of EP ameliorated the microstructure and decreased the crystal diffraction peak area of TS gel. Infrared spectroscopy results revealed EP modified the above properties of TS by hydrogen bonds and non-covalent forces. Furthermore, EP inhibited the in vitro digestion of TS paste. Using taro balls as TS-based food model, appropriate addition of EP (0.10 %) improved texture properties, frozen storage stability and color of samples. The present results can not only facilitate the understanding of the modification mechanism of EP on the properties of TS, but also induce the burgeoning of starchy products and the possible application of EP in foods., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Myocardial infarction (MI) can lead to higher cellular damage, making cell-free DNA (cfDNA) a potential biomarker for assessing disease severity. The aim of this study is to evaluate survival predictions using cfDNA measurements and assess its correlation with MI., Materials and Methods: A direct fluorescence assay was employed to measure cfDNA content in the blood samples of participants. The inclusion criteria included patients who gave informed consent, suffering from ST-elevation myocardial infraction (STEMI) based on established diagnostic criteria (joint ESC/ACC guidelines), between the age of 18 and 80 years old, and had elevated troponin biomarker levels. The study included 150 patients diagnosed with STEMI and 50 healthy volunteers as controls. Serial monitoring of patients was conducted to track their postdisease status. The rate of change of cfDNA was calculated and daily measurements for 7 days were recorded., Results: Mean levels of cfDNA were found to be 5.93 times higher in patients with STEMI compared to healthy controls, providing clear evidence of a clinical correlation between cfDNA and STEMI. Patients were further categorized based on their survival status within a 90-day period. The study observed a strong predictive relationship between the rate of change of cfDNA during daily measurements and survival outcomes. To assess its predictive capability, a receiver operating characteristics (ROC) curve analysis was performed. The ROC analysis identified an optimal cutoff value of 2.50 for cfDNA, with a sensitivity of 81.5% and specificity of 74.0% in predicting disease outcomes., Conclusion: This study demonstrates a robust association between cfDNA and STEMI, indicating that cfDNA levels can be a valuable early prognostic factor for patients. Serial measurements of cfDNA during early disease onset hold promise as an effective approach for predicting survival outcomes in MI patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Research in Medical Sciences.)

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Effects of structural characteristics of phenolic compounds on the oxidation of glycerol trioleate were investigated, and the action rule and mechanism were further explored. By using thermal and multispectral analyses, all tested phenolic compounds significantly inhibited the oxidation of glycerol trioleate, and reduced the decomposition of CC and ester bonds of glycerol trioleate, which were attributed to their capability to inhibit the production of free radicals. Quercetin and gallic acid were the most effective among the condensed and hydrolyzable phenolic compounds in present study, respectively. For condensed phenolic compounds, the hydroxyl groups in B ring, substitution in C ring, and the structure of C ring played a crucial role in their inhibitory action. For hydrolyzable phenolic compounds, the amount of hydroxyl groups and their molecular weight had obvious effects on their inhibitory action. According to the measurement of molecular electrostatic potential and frontier molecular orbitals by density functional theory, the large maximum electrostatic potential and the small energy gap value were beneficial to enhance the inhibitory capability of phenolic compounds on the oxidation of glycerol trioleate. All present results suggested the potential action rule and molecular mechanism about the inhibitory effects of phenolic compounds on the oxidation of glycerol trioleate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa , the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease - most prominently renal anemia and renal fibrosis - have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro . Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-κB inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-κB p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-κB, and then inhibited the expression of IL-6, p-STAS3, TGF-β1 protein. Therefore, CAT can regulate Nrf2/NF-κB signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys.

Objective: Based on the interactions between immune components in the tumor microenvironment and ovarian cancer (OC) cells, immunotherapies have been demonstrated to be effective in dramatically increasing survival rates. This study aimed to identify landmark genes, develop a prognostic risk model, and explore its relevance to the efficacy of immunotherapy., Materials and Methods: A risk model was built based on the immune- and stromal-related genes, which were extracted from the OC gene expression data of "The Cancer Genome Atlas" (TCGA) database. Survival analysis and receiver operating characteristic (ROC) analysis were then conducted through the model's risk score pattern, which was established depending on the TCGA training cohort and verified based on the internal TCGA cohort and external "Gene Expression Omnibus" (GEO) datasets. Furthermore, the immune-related characteristics and prognostic values of the risk model were evaluated., Results: The prognostic risk model for ovarian cancer demonstrated excellent performance in predicting survival rates, as validated in both the TCGA and GEO databases. The model showed significant associations with 17 functional immune cells, 17 immune checkpoints, PD-1, and several immune pathways, suggesting its potential to enhance the efficacy of immunotherapy in OC., Conclusions: The risk model developed in this study has the potential to serve as a prognostic marker for OC, enabling the development of personalized immunotherapy protocols and providing a theoretical basis for novel combinations of immunotherapeutic approaches.

By resorting to the principle of remote activation, we herein demonstrate the first photoredox catalyzed (3+3) dipolar cycloaddition of nitrones with aryl cyclopropanes. Key to the fidelity of the reaction resides in a facile manner of substrate activation by single-electron transfer (SET) oxidation with photoredox catalysis, and the reaction takes place through a stepwise cascade encompassing a three-electron-type nucleophilic substitution triggered cyclopropane ring-opening and a diastereoselective 6-endo-trig radical cyclization manifold. The reaction proceeds under mild conditions with excellent regio- and stereoselectivity, nicely complementing the well-developed Lewis acid catalyzed cycloaddition of donor-acceptor cyclopropanes. Other merits of the protocol include wide scope of aryl cyclopropanes with diversified substitution patterns and good functional-group compatibility. A mechanism involving an aryl radical cation promoted remote activation mode was also proposed and supported by mechanistic experiments., (© 2023 Wiley-VCH GmbH.)

Influences of structural characteristics of phenolic compounds on the properties of potato starch were investigated, and their effects on the quality, function, and digestion of potato starch noodles were further determined. All testing phenolic compounds (including protocatechuic acid [PA], naringin [NA], and tannic acid [TA]) exhibited the significant capability to modify the thermal properties, rheological properties, and enzymatic hydrolysis of potato starch. The high amount of hydroxyl groups, the presence of glycoside structure, appropriate molecular size, and steric hindrance were beneficial to enhance their effects on potato starch. In addition, by changing the microstructure of starch hydrocolloids, PA, NA, and TA could affect the color, texture properties, and cooking properties of potato starch noodles. Meanwhile, PA and TA could endow potato starch noodles with remarkable antioxidant activity. Furthermore, the in vitro digestion of potato starch noodles was obviously inhibited by phenolic compounds, especially for TA. All present results suggested that structural characteristics of phenolic compounds affected their interaction affinity and combination degree with potato starch molecules, so as to modify the properties of starch and affect the quality, function, and digestion of starchy foods, which showed the valuable applications in food and chemical industries. PRACTICAL APPLICATION: The property, function, and digestion characteristics of potato starch show the significant effects on the quality of potato starch products in food industry. In present study, the thermal properties, rheological properties, and enzymatic hydrolysis of potato starch were modified by different phenolic compounds (including protocatechuic acid, naringin, and tannic acid) in varying degrees, whereas the quality, antioxidant activity, and digestion characteristic of potato starch noodles were modified by phenolic compounds with different structures. All results showed the potential application and interaction regularities of phenolic compounds as natural additives for potato starch processing in food industry., (© 2023 Institute of Food Technologists.)

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Effects of tea polyphenols (TP) on the physical properties, barrier properties and functionality of potato starch-based film were determined, while the interaction mechanism between TP and starch in film and the application of this film in fruit packaging were further evaluated. TP exhibited different effects on the physical properties of potato starch-based film, including thickness (0.083 to 0.087 mm), moisture content (9.27% to 9.68%), color (Δ E value: 5.41 to 10.55), light transmittance (51% to 62%), tensile properties and thermal properties, and improved its barrier properties, including water vapor permeability (9.68 to 11.84 × 10 - 11 g m - 1 s - 1 Pa - 1 ),oxygen permeability (1.25 to 2.78 × 10 - 16 g m - 1 s -1 Pa - 1 ) and antioxidant activity. According to the determination of wide-angle X-ray diffraction, Fourier transform infrared and scanning electron microscope, TP could interact with starch chains via hydrogen bonds to form non-crystal complexes, thus affecting the cross-linking among starch chains and further changing the microstructure of film. Furthermore, film incorporated with TP could improve the storage quality (including weight and texture) of blueberries, and inhibit the enzymatic browning of fresh-cut bananas during storage. All present results suggested that tea polyphenols had potential to enhance the properties and function of potato starch-based film, and the film exhibited the application prospect in fruit packaging and preservation.

Background: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity., Methods: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively., Results: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency., Conclusions: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants., (© 2022. The Author(s).)

Network theory has attracted much attention from the biological community because of its high efficacy in identifying tumor-associated genes. However, most researchers have focused on single networks of single omics, which have less predictive power. With the available multiomics data, multilayer networks can now be used in molecular research. In this study, we achieved this with the construction of a bilayer network of DNA methylation sites and RNAs. We applied the network model to five types of tumor data to identify key genes associated with tumors. Compared with the single network, the proposed bilayer network resulted in more tumor-associated DNA methylation sites and genes, which we verified with prognostic and KEGG enrichment analyses.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We investigated the modification of wheat starch with Ligustrum robustum (Rxob.) Blume extract (LRE) and determined the action mechanism. Based on differential scanning calorimetry, LRE decreased the gelatinization enthalpy of wheat starch from 19.14 to 7.15 J/g and changed gelatinization temperatures (including the variation in gelatinization onset temperature, peak temperature and conclusion temperature in different degrees). Moreover, LRE affected the pasting viscosity curve of wheat starch, and changed its rheological parameters (including the decrease in storage modulus and loss modulus, as well as the increase in loss tangent). Based on the analysis of scanning electron microscopy and wide-angle X-ray diffraction, LRE increased the hole size and the roughness of the gel microstructure, and decreased the crystallinity of wheat starch. Meanwhile, the evaluation results of the texture analyzer and the colorimeter showed that LRE could change the quality properties (including decrease hardness, fracturability and L* values, as well as increase a* and b* values) of wheat starch biscuits after hot air baking (170 °C). Furthermore, with molecular dynamics simulation analysis, phenolic compounds of LRE combined with starch molecules via H-bonds and affected the formation of molecular bonds (including intra- and intermolecular hydrogen bonds), so as to change the spatial conformation and properties of wheat starch during gelatinization and retrogradation. The present results suggest that LRE can modify the physicochemical properties of wheat starch and further improve its processing properties, indicating its potential in the design and development of starch foods (such as steamed buns, bread, biscuits, etc.).

The potential uses of Ligustrum robustum (Rxob.) Blume extract as a natural antioxidant to protect the quality of different oils during storage and frying process were studied. The results showed that L. robustum extract has been shown to retard the decline in the quality of both oils based on the tests of acid value, peroxide value, p-anisidine value, color, volatile flavor, and fatty acid compositions, and the protective effect of L. robustum extract on the quality of peanut oil was better than that of palm oil. By the component analysis, L. robustum extract was found to have a total phenols content of 140.75 ± 1.52 mg/g, and ligurobustoside C was identified as the main phenolic compound. The thermogravimetric and differential scanning calorimetry results showed that L. robustum extract enhanced the oxidative stability of peanut and palm oils. In addition, Fourier transform infrared results indicated that L. robustum extract had protective effects on the C=C bond and ester bond of oil molecule. Moreover, by using electron spin resonance technique, L. robustum extract showed the ability to inhibit and scavenge alkyl-free radicals in both oils. The present results suggested that L. robustum extract may protect the quality of oils during the storage and frying process by inhibiting the oxidation of unsaturated fatty acids and might be a potential natural antioxidant in the food industry. PRACTICAL APPLICATIONS: The excellent antioxidant ability of Ligustrum robustum (Rxob.) Blume extract on the oxidation of different oils and its low price indicated that it could be used as a new low-cost natural antioxidant in oil processing., (© 2022 Institute of Food Technologists®.)

Edible and medicinal mushrooms are extensively cultivated and commercially consumed around the world. However, green mold disease (causal agent, Trichoderma spp.) has resulted in severe crop losses on mushroom farms worldwide in recent years and has become an obstacle to the development of the Ganoderma industry in China. In this study, a new species and a new fungal pathogen on Ganoderma sichuanense fruitbodies were identified based on the morphological characteristics and phylogenetic analysis of two genes, the translation elongation factor 1-α (TEF1) and the second-largest subunit of RNA polymerase II (RPB2) genes. The new species, Trichoderma ganodermatigerum sp. nov., belongs to the Harzianum clade, and the new fungal pathogen was identified as Trichoderma koningiopsis . Furthermore, in order to better understand the interaction between Trichoderma and mushrooms, as well as the potential biocontrol value of pathogenic Trichoderma , we summarized the Trichoderma species and their mushroom hosts as best as possible, and the phylogenetic relationships within mushroom pathogenic Trichoderma species were discussed.

Background: Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue., Methods: The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes., Discussion: The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100047932 . Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021., (© 2022. The Author(s).)

Introduction: Rheumatoid arthritis (RA) has a huge societal impact due to the high prevalence, irreversible joint damage and systemic complications. Gut microbiota plays an important role in the pathogenesis and progression of RA by regulating the host immune system. Restoring intestinal homeostasis by altering the microbiota could be an attractive strategy for the prevention and treatment of RA. However, the signature features of microbial dysbiosis in RA are still controversial. Therefore, we aim to elucidate the characteristic change in the diversity and composition of gut microbiota in RA., Methods and Analysis: We will systematically search through PubMed, EMBASE, Web of Science and Cochrane Library, as well as dissertations and conference proceedings. The reference lists of all included studies will be also reviewed to retrieve additional relevant studies. The case-control studies that reported either the relative abundance of bacteria at the phylum or genus level or at least one of the alpha-diversity, beta-diversity indexes in both RA and healthy controls will be included. Eligible studies will be screened independently by two reviewers according to the inclusion criteria. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of the included studies. Data extraction, qualitative and quantitative analysis will be performed within the gut microbial dysbiosis in RA. The expected outcomes will be the identification of the specific changes in composition and diversity of the gut microbiota in patients with RA. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation framework., Ethics and Dissemination: Ethical approval is unnecessary as this review does not address the data and privacy of patients. The results will be published in a peer-reviewed scientific journal and conference presentations., Prospero Registration Number: CRD42021225229., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Acute pain is a prevalent problem for dementia residents in nursing homes. A variety of intervention strategies have been applied to address this problem. However, there remains an issue of inadequate pain control. This study aims to explore the analgesic efficacy of auricular acupressure (AA) for dementia residents with acute pain in nursing homes., Methods: A multicenter, single-blind, randomized, and sham-controlled clinical trial was performed in three nursing homes in Yinchuan, China. All of the 206 eligible patients with acute pain were randomly divided into two groups for real AA therapy or sham AA (at sham point stimulation) therapy. The primary outcome was measured with a face pain scale revised (FPS-R) score before the procedure, 5 min after the start of the intervention, and 5 min after finishing the procedure. Secondary outcomes covered three physiological parameters, adverse reactions observed, satisfaction level of caregivers, acceptance of patients, and additional use of analgesics., Results: There was a significant difference in pain scores based on FPS-R between the two groups ( p < 0.01). Pain score in the true AA group was 1.84 ± 0.23, compared with 2.22 ± 0.81 in the sham AA group. No adverse events were found during the whole procedure for all patients. The satisfaction level of caregivers and acceptance of patients in the real AA group were significantly higher than those in the sham AA group., Conclusion: This study shows that real AA was an alternative analgesic modality in reducing acute pain in patients with mild dementia., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Jun-Jun Zhang et al.)

Ligustrum robustum (Rxob.) Blume is traditionally served as a functional tea in China. In this work, the antioxidant activities of L. robustum (Rxob.) Blume extract (LRE) were evaluated and its inhibitory effect and mechanism on pancreatic lipase were further investigated. With the high contents of phenols (139.70 ± 1.41 mg gallic acid equivalent/g extract) and flavonoids (326.46 ± 7.36 mg rutin equivalent/g extract), LRE showed significant antioxidant activities (p < 0.05) for scavenging free radicals and hydrogen peroxide, inhibiting lipid peroxidation and providing strong reducing power. Meanwhile, LRE displayed remarkable inhibitory activity on pancreatic lipase with a low half-effective inhibitory concentration (IC 50 ) of 2.469 ± 0.005 mg/ml which was further determined as non-competitive inhibition. The spectroscopic results showed that LRE inhibited the activity of pancreatic lipase by modifying the tertiary and secondary structures of lipase. Moreover, four phenolic compounds (acteoside, lipedoside A, oleuropein and ligurobustoside C) were identified from LRE by the high performance liquid chromatography-quadrupole- time of flight-mass spectrometry. In addition, according to molecular docking analysis, the four phenols could interact with pancreatic lipase by hydrogen bonds, so as to change the spatial structure of pancreatic lipase and inhibit its catalytic activity. The present results suggest that LRE not only exhibits strong antioxidant capacity but possesses effectively inhibitory activity on pancreatic lipase, which might have the potential to be developed as functional food and nutraceuticals for the prevention of metabolic diseases. PRACTICAL APPLICATION: Ligustrum robustum (Rxob.) Blume extract has been confirmed to possess antioxidant activity and lipase inhibitory activity, which indicates that the L. robustum extract has the potential to prevent oxidative stress and regulate fat metabolism. This work suggests that L. robustum extract can be served as a novel resource to prepare nutraceuticals and functional food in food industries., (© 2022 Institute of Food Technologists®.)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell non-Hodgkin lymphoma in adults and the pathogenesis of DLBCL is multifactorial and complex. Understanding the molecular mechanisms involved in DLBCL is important to identify new therapeutic targets. The present study aimed to screen and identify differentially expressed microRNAs (miRNAs/miRs) between diffuse large B-cell lymphoma (DLBCL) and control [lymph node reactive hyperplasia (LRH)] groups, and to investigate whether miRNAs associated with DLBCL could serve as potential therapeutic targets. In total, 5 DLBCL experimental samples and 5 control samples were obtained from fresh patient tissues. Firstly, the fresh samples were analyzed using miRNA microarray to identify differentially expressed miRNAs. Next, three databases (TargetScan, microRNA.org and PITA) were used to predict by intersection the potential target genes of the 204 differential miRNAs identified, and a Venn diagram of the results was performed. Subsequently, the target genes of differential miRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, to validate the miRNA microarray data, reverse transcription-quantitative PCR (RT-qPCR) was performed for 8 differentially expressed miRNAs (miR-193a-3p, miR-19a-3p, miR-19b-3p, miR-370-3p, miR-1275, miR-490-5p, miR-630 and miR-665) using DLBCL and LRH fresh samples. In total, 204 miRNAs exhibited differential expression, including 105 downregulated and 54 upregulated miRNAs. The cut-off criteria were set as P≤0.05 and fold-change ≥2. A total of 7,522 potential target genes for the 204 miRNAs were predicted. Potential target genes were enriched in the following pathways: 'Cancer', 'MAPK signaling pathway', 'regulation of actin cytoskeleton', 'focal adhesion', 'endocytosis', 'Wnt signaling pathway', 'axon guidance', 'calcium signaling pathway' and 'PI3K/AKT signaling pathway'. A total of 8 miRNAs were validated by RT-qPCR, and 4 miRNAs (miR-19b-3p, miR-193a-3p, miR-370-3p and miR-490-5p) exhibited low expression levels in DLBCL (P<0.05), while miR-630 was highly expressed in DLBCL (P<0.05). Overall, the present study screened 204 differentially expressed miRNAs and analyzed the expression levels of 8 differentially expressed miRNAs in DLBCL. These differentially expressed miRNAs may serve as therapeutic targets for improvement of therapeutic efficacy in DLBCL in the future., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gao et al.)

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56 bri CD16 - natural killer (NK) cells and upregulation of interferon-gamma in effector CD4 + and CD8 + T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4 + T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections., (© 2021. The Author(s).)

Aims: A growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma., Methods: Expression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson's X 2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson's or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis., Results: High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients., Conclusion: Our research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features., Methods: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations., Results: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis., Conclusions: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.

Central nervous system (CNS) lymphoma is an extranodal non-Hodgkin B-cell lymphoma characterized by malignant lymph tissue arising in the brain or spinal cord, associated with inflammation and blood-brain barrier (BBB) disruption. Although BBB disruption is known to occur in patients with CNS lymphoma, a direct link between these two has not been shown. Herein, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model. Functional enrichment analysis of unbiased cerebrospinal fluid proteomics of CNS B-cell lymphoma patients showed that coagulation protein networks were highly connected with tumor-associated biological signaling pathways. In vivo two-photon imaging demonstrated that lymphoma growth was associated with BBB disruption, and in vitro experiments identified a role for fibrinogen in promoting lymphoma cell adhesion. Overall, these results identify perivascular lymphoma clustering at sites of fibrinogen deposition, and suggest that fibrinogen may be a target for pharmacologic intervention in metastatic B-cell lymphoma associated with BBB disruption., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Cutaneous T-cell lymphoma is a form of non-Hodgkin lymphoma that manifests initially in the skin and disseminates systemically as the disease progresses. Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma. Advanced mycosis fungoides and Sézary syndrome are life threatening with few treatment options. We searched for new agents by high-throughput screening of selected targeted compounds and identified high-value targets, including phosphatidylinositol 3-kinase (PI3K) and cyclin-dependent kinases. To validate these hits from the screen, we developed patient-derived xenograft mouse models that recapitulated the cardinal features of mycosis fungoides and Sézary syndrome and maintained histologic and molecular characteristics of their clinical counterparts. Importantly, we established a blood-based biomarker assay using tumor cell-free DNA to measure systemic tumor burden longitudinally in living mice during drug therapy. A PI3K inhibitor, BKM120, was tested in our patient-derived xenograft model leading to disease attenuation and prolonged survival. Isoform-specific small interfering RNA knockdowns and isoform-selective PI3K inhibitors identified PI3K-δ as required for tumor proliferation. Additional studies showed a synergistic combination of PI3K-α/δ inhibitors with histone deacetylase inhibitors. The strong preclinical efficacy of this potent combination against multiple patient-derived xenograft models makes it an excellent candidate for further clinical development., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induce antibody production, six of these are immunodominant epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the immunodominant epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses., Competing Interests: Declaration of interests R.-t.L, S.L., and X.-x.X. have filed a provisional patent on epitopes for designing a coronavirus vaccine., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Inflammatory myofibroblastic tumor (IMT) is a distinct tumor with a low incidence rate, which can be diagnosed at any age with a predilection for children and adolescents. Although IMT is visible in any tissues and organs, it is more commonly found in the lungs. The clinical and radiological manifestations of IMT lack specificity, hence resulting in frequent misdiagnosis. Surgical resection is currently the main therapeutic approach for IMT. Only scarce cases of IMT treated with metformin have been reported. Here we report the case of an IMT patient with partial penile resection treated with metformin., Case Summary: A 1-year-old boy was born with a shorter penis, and his foreskin could not be completely turned over. When he was 6 month old, a well-circumscribed mass on the glans was found, while it did not attract the attention of his parents. The mass gradually increased in size over time before he was admitted to the hospital, where physical examination was performed. It was revealed that the glans hidden behind the foreskin had a mass with a diameter of about 4 cm surrounding the penis. The mass appeared to be hard with a smooth surface and poor mobility. The two testicles examined at the bottom of the scrotum were revealed to have a normal size. Magnetic resonance imaging showed a tumor with rich blood supply encircling the cavernosum with a size of 3.5 cm × 2.1 cm × 2.0 cm. A thick urinary line was found without urine dripping, urgency, and urodynia. Surgical treatment was performed. During the operation, it was observed that the mass had surrounded and invaded the cavernosum without obvious boundaries, and that the tumor occupied about one-half of the penis cross-section as well as infiltrated more than one-half of the glans. In addition, the tumor had caused urethral invasion and anterior urethrostenosis. With the intention of keeping the glans and cavernosum, the tumor at the anterior urethra was partially removed, leaving about 30% of the tumor mass. Pathology analysis demonstrated that the tumor was rich in spindle cells with infiltration of inflammatory cells. Immuno-histochemistry analysis indicated that the cells were positive for CD4, CD99, Ki67, BCL2, and CD68, and negative for ALK, MyoG, S100, SOX10, PR, and EMA. Hence, the tumor was diagnosed as IMT. Metformin was prescribed for the patient after the operation, following which an oral dose of 7 mg/kg was given three times a day after meals. Three months later, it was observed that the remaining tumor had completely disappeared and that the urination process from the urethra opening had resumed normal. In addition, there were no side effects observed. There was also no tumor recurrence. The growth and development of the boy were unaffected as a result of the treatment., Conclusion: The tumor was observed to have completely disappeared after treatment with metformin. Our finding is of great significance to facilitate future clinical treatment with IMT., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The pain management of postherpetic neuralgia (PHN) remains a major challenge, with no immediate relief. Nitrous oxide/oxygen mixture has the advantages of quick analgesic effect and well-tolerated. The purpose of this study is to investigate the analgesic effect and safety of nitrous oxide/oxygen mixture in patients with PHN., Methods/design: This study is a single-center, two-group (1:1), randomized, placebo-controlled, double-blind clinical trial. A total of 42 patients with postherpetic neuralgia will be recruited and randomly divided into the intervention group and the control group. The control group will receive routine treatment plus oxygen, and the intervention group will receive routine treatment plus nitrous oxide/oxygen mixture. Data collectors, patients, and clinicians are all blind to the therapy. The outcomes of each group will be monitored at baseline (T0), 5 min (T1), and 15 min (T2) after the start of the therapy and at 5 min after the end of the therapy (T3). The primary outcome measure will be the pain intensity. Secondary outcomes included physiological parameters, adverse effects, patients' acceptance of analgesia, and satisfaction from patients., Discussion: Previous studies have shown that nitrous oxide/oxygen mixture can effectively relieve cancer patients with breakthrough pain. This study will explore the analgesic effect of oxide/oxygen mixture on PHN. If beneficial to patients with PHN, it will contribute to the pain management of PHN., Trial Registration: Chinese Clinical Trial Register ChiCTR1900023730 . Registered on 9 June 2019.

Aim: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess., Design: This protocol is a randomized, double-blind, placebo-controlled trial., Methods: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients., Discussion: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven., Impact: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China., (© 2020 John Wiley & Sons Ltd.)

The effects and action mechanism of tea polyphenols (TP) on the quality of rapeseed oil during frying process were investigated. Results showed that compared with control, TP (0.04%, w/w) exhibited the remarkable ability to inhibit the deterioration of acid value, peroxide value, anisidine value, viscosity, and color of frying oil. By using gas chromatography-mass spectrometry, frying oil with TP showed the higher content of unsaturated fatty acids (72.79%) and lower content of trans fatty acids (3.36%) than those of control. Meanwhile, frying oil with TP had a higher total phenolic content than control at the same frying time. In addition, the thermo gravimetric-differential scanning calorimetry results showed that TP could increase the oxidation stability of rapeseed oil. Furthermore, according to the Fourier transform infrared and molecular dynamic simulation results, TP could reduce the breaking degree of = C-H bond, C-O-C bond, and C = C bond in oil molecules, and inhibit the oxidation of oil components by inhibiting the generation of free radicals and eliminating free radicals. All present results suggested that TP showed the potential value to be used for protecting the quality of oil during the frying process in food and chemical industries. PRACTICAL APPLICATIONS: The inhibitory effect of tea polyphenols on the deterioration of quality of rapeseed oil during frying was found and the mechanism had also preliminarily interpretation. This work provided a method for monitoring the quality of fry oil and provided the theoretical basis for the use of tea polyphenols in frying., (© 2020 Institute of Food Technologists®.)

Hub proteins related with Hippo signal pathway in glioma were investigated using proteomics methods (Tandem Mass Tag, TMT) to determine the differentially expressed proteins in glioblastoma (GBM). Ingenuity Pathway Analysis (IPA) was performed to complement proteomic findings by identifying the top canonical pathways as well as to suggest novel proteins for the targeted therapy of glioma. A total of 222 formalin-fixed paraffin-embedded (FFPE) glioma tissue samples were used to verify the expression of protein phosphatase 1γ (PP1γ), Yes-associated protein 1 (YAP1), and SOX2 via immunohistochemistry. Bioinformatics analysis revealed these proteins as crucial in the Hippo signaling pathway in GBM. Spearman correlation was performed to analyze the relationship of these three proteins, and survival analysis was conducted to investigate their effects on prognosis. Among the 5808 proteins identified by TMT with the standard of P-value < 0.05 and fold change (FC) of>1.2 or <0.83, 1398 upregulated and 1060 downregulated differentially expressed proteins were found. IPA revealed that the Hippo signaling was activated in the top 10 canonical pathways, and PP1γ was activated in the Hippo signaling. Immunohistochemistry analysis indicated that PP1γ, YAP1, and SOX2 were highly and positively expressed in glioma. PP1γ expression was related to WHO grade (p = 0.003) and ki-67 expression (p = 0.012). Low PP1γ expression was associated with IDH1-mut in low-grade glioma (LGG; WHO grades II and III) (p = 0.037). PP1γ was positively correlated with YAP1 (p < 0.001; r = 0.259) and SOX2 (p = 0.009; r = 0.175). In survival analysis, age, WHO grade, ki-67 expression, and PP1γ expression independently predicted a short OS in total cohort (p < 0.05). Therefore, PP1γ is a hub protein associated with Hippo signal pathway in glioma, and its expression indicates poor prognosis in patients with glioma. Therefore, PP1γ may be a promising prognostic biomarker and a therapeutic target in glioma., (Copyright © 2020. Published by Elsevier GmbH.)