Steam Explosion-Assisted Extraction of Polysaccharides from Pleurotus eryngii and Its Influence on Structural Characteristics and Antioxidant Activity.

Pleurotus eryngii (PE) has been sought after for its various health benefits and high content of phenolic compounds. This study explored the feasibility of steam explosion (SE)-assisted extraction of polysaccharides with high antioxidant capacities from PE. An orthogonal experimental design (OED) was used to optimize the SE-assisted extraction of PE. The influence of the optimized SE-assisted extraction on the physicochemical properties of PE polysaccharides was determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), monosaccharide compositional analysis and antioxidant capacity assays. Under optimal SE conditions, SE-assisted extraction increased the polysaccharide yield by 138% compared to extraction without SE-assistance. In addition, SEM demonstrated that SE-assisted extraction markedly altered the spatial structure of Pleurotus eryngii polysaccharides (PEP), and monosaccharide compositional analysis revealed that this pretreatment significantly increased the proportions of some monosaccharides, such as glucose, rhamnose and arabinose, in the isolated PEP. FTIR spectra indicated no change in the major chemical functional groups of PEP. PEP extracted by SE-assisted extraction had significantly increased free radical scavenging and antioxidant capacities. In conclusion, SE-assisted extraction appears to be a novel polysaccharide extraction technology, which markedly increases extraction yields and efficiency and can increase the biological activity of polysaccharide extracts.

Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer.

Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.

A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer.

Poly ADP-ribose polymerase (PARP) inhibitors are effective therapies for cancer patients with homologous recombination (HR) deficient tumors. The imipridone ONC206 is an orally bioavailable dopamine receptor D2 antagonist and mitochondrial protease ClpP agonist that has anti-tumorigenic effects in endometrial cancer via induction of apoptosis, activation of the integrated stress response and modulation of PI3K/AKT signaling. Both PARP inhibitors and imipridones are being evaluated in endometrial cancer clinical trials but have yet to be explored in combination. In this manuscript, we evaluated the effects of the PARP inhibitor olaparib in combination with ONC206 in human endometrioid endometrial cancer cell lines and in a genetically engineered mouse model of endometrial cancer. Our results showed that simultaneous exposure of endometrial cancer cells to olaparib and ONC206 resulted in synergistic anti-proliferative effects and increased cellular stress and apoptosis in both cell lines, compared to either drug alone. The combination treatment also decreased expression of the anti-apoptotic protein Bcl-2 and reduced phosphorylation of AKT and S6, with greater effects compared to either drug alone. In the transgenic model of endometrial cancer, the combination of olaparib and ONC206 resulted in a more significant reduction in tumor weight in obese and lean mice compared to ONC206 alone or olaparib alone, together with a considerably decreased Ki-67 and enhanced H2AX expression in obese and lean mice. These results suggest that this novel dual therapy may be worthy of further exploration in clinical trials.

Comparison of Primary B/NKT Non-Hodgkin Lymphomas in Nasopharynx, Nasal Cavity, and Paranasal Sinuses.

OBJECTIVE: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity (NC), nasopharynx, and paranasal sinuses, which are always categorized as one sinonasal type. STUDY DESIGN: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from Surveillance, Epidemiology, and End Results (SEER) database were included (1975-2017). SETTING: Population-based cohort study. METHODS: We conducted univariate and multivariate Cox regressions and Kaplan-Meier analysis to examine survival outcomes of B/NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses, respectively. RESULTS: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the cancer-special survival (CSS) outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (Hazard ratio [HR]: 3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of a higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in the nasopharynx NKT-NHL. However, chemotherapy has only been beneficial for CSS in patients with paranasal sinuses B-NHL (HR: 0.42) since 2010, rather than in other types of B/NKT-NHL. CONCLUSION: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinicodemographics and prognoses are largely different and should be treated and studied as distinct diseases.

TIPE2 acts as a tumor suppressor and correlates with tumor microenvironment immunity in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is one of the deadliest gynecologic cancers. The etiology of EOC has still not been elucidated thoroughly. Tumor necrosis factor-α-induced protein 8-like2 (TNFAIP8L2, TIPE2), an important regulator of inflammation and immune homeostasis, plays a critical role in the progression of various cancers. This study aims to investigate the role of TIPE2 in EOC. METHODS: Expression of TIPE2 protein and mRNA in EOC tissues and cell lines was examined using Western blot and quantitative real-time PCR (qRT-PCR). The functions of TIPE2 in EOC were investigated by cell proliferation assay, colony assay, transwell assay, and apoptosis analysis in vitro. To further investigate the regulatory mechanisms of TIPE2 in EOC, RNA-seq and western blot were performed. Finally, the CIBERSORT algorithm and databases including Tumor Immune Single-cell Hub (TISCH), Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction (TISIDB), and The Gene Expression Profiling Interactive Analysis (GEPIA) were used to elucidate its potential role in regulating tumor immune infiltration in the tumor microenvironment (TME). RESULTS: TIPE2 expression was shown to be considerably lower in both EOC samples and cell lines. Overexpression of TIPE2 suppressed EOC cell proliferation, colony formation, and motility in vitro. Mechanistically, TIPE2 suppressed EOC by blocking the PI3K/Akt signaling pathway, according to bioinformatics analysis and western blot in TIPE2 overexpression EOC cell lines, and the anti-oncogenic potentials of TIPE2 in EOC cells could be partially abrogated by the PI3K agonist, 740Y-P. Finally, TIPE2 expression was positively associated with various immune cells and possibly involved in the regulation of macrophage polarization in ovarian cancer. CONCLUSIONS: We detail the regulatory mechanism of TIPE2 in EOC carcinogenesis, as well as how it correlates with immune infiltration, emphasizing its potential as a therapeutic target in ovarian cancer.

A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation: A methodological issue.

AIM: After reading the article by Ivan K. Poon et al. Certain issues regarding the methodology must be addressed. RESULT: First, it was not sufficient using only sensitivity and specificity. Second, we think the receiver operator characteristic curve (ROC) as well as the index of area under curve (AUC) could better be demonstrated in this, it was not sufficient using only sensitivity and specificity. Second, we think the receiver operator characteristic curve (ROC) as well as the index of area under curve (AUC) could better be demonstrated in this article for a more comprehensive understanding of this diagnostic test accuracy when comparing different tests. CONCLUSION: With using more comprehensive indexes including Youden's index, LR and AUC, the conclusions of Ivan K. Poon and his colleagues would be sodified.

Leptin Promotes HTR-8/SVneo Cell Invasion via the Crosstalk between MTA1/WNT and PI3K/AKT Pathways.

The process of placental invasion is essential for a successful pregnancy. Leptin is involved in trophoblast invasiveness, and its dysregulation is connected with a series of diseases, including preeclampsia. However, the knowledge of the precise mechanisms in leptin-induced trophoblast invasiveness is still limited. According to the present research, transwell assay suggested that leptin is a dose- and time-dependent regulator in inducing HTR-8/SVneo cell invasion. Western blot analysis and immunofluorescence staining revealed that leptin-induced MMP9 expression is essential in the invasion process of HTR-8/SVneo cells. Mechanistically, we demonstrated that leptin activated ß-catenin via the crosstalk between the MTA1/WNT and PI3K/AKT pathways. Besides, we showed that downregulating the key molecules in the signaling pathways by siRNA can inhibit leptin-induced MMP9 expression and further suppress invasion of HTR-8/SVneo cells. In conclusion, our study revealed a new regulatory mechanism of leptin-induced HTR-8/SVneo cell invasiveness and will provide novel insights into the causes and potential therapeutic targets for diseases related to dysregulation of trophoblast invasion in the future.

Fetal Congenital Cardiac and Vascular Disorders Associated with Sertraline Treatment during Pregnancy: Analysis of FAERS Data.

Objective: Sertraline is one of the most commonly used antidepressants worldwide and is one of the first-choice treatments for depression during pregnancy. This study is aimed at testing the possible association between sertraline intrauterine exposure and congenital cardiac and vascular disorder occurrences by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analysis and Bayesian analysis were used to mine FAERS for suspected congenital cardiac and vascular disorder data for sertraline intrauterine exposure from the first quarter of 2004 to the second quarter of 2021. Results: Among the 914 cases of sertraline used with congenital cardiovascular disease in the FAERS database, the reporting areas were mainly in the United States and Europe. The number of adverse events reported every year since 2004 has no many differences. Congenital anomalies are the most frequently reported serious clinical outcome. Among the 69 positive signals detected from 914 cases, 31 were invalid signals, and 38 were valid signals according to criteria. The most common ones are heart disease congenital, atrial septal defect, ventricular septal defect, patent ductus arteriosus, and persistent fetal circulation. Conclusions: Mining FAERS data can analyze and study the adverse reactions of sertraline in a more comprehensive and in-depth manner, thereby effectively reducing the risk of clinical medication.

Survival Outcomes Related to Treatment Modalities in Patients With Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: More patients with oropharyngeal squamous cell carcinoma (OPSCC) in Eastern countries receive surgically inclusive treatment (SIT), while most patients in Western countries receive nonsurgical treatment (NST). The optimal treatment modality for OPSCC patients remains controversial. METHODS: A total of 153 consecutive OPSCC cases diagnosed between 2009 and 2019 in West China Hospital (WCH) and 15,400 OPSCC cases from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2017) were obtained. Clinical characteristics, treatments, and survival outcomes were retrospectively collected. We constructed Kaplan-Meier curves and performed univariate (UVA) and multivariate (MVA) analyses to compare the prognosis of OPSCC patients among the WCH, SEER Asian, and SEER all ethnic populations by different treatment modality, human papilloma virus (HPV) infection status, age, and tumor stage. RESULTS: Overall, the proportions of patients with younger age, advanced tumors and HPV-negative status, and receiving SIT in WCH population were higher than those in the SEER all ethnic population, while the proportions in the SEER Asian population were between those of the other two populations. We observed consistent beneficial effects of SIT on the overall survival (OS) in OPSCC patients in all three populations (SEER Asian: MVA, hazard ratio (HR): 0.2, p < .001; SEER all ethnic: MVA, HR: 0.46, p < .001; WCH: UVA, HR: 0.62, p = .071), and HPV-negative Asian patients showed greater benefits from the SIT than HPV-positive Asian patients (HPV Negative: HR: 0.16, p = .005; HPV positive: HR = 0.28, p = .059). Male was a risk factor for reduced OS in OPSCC patients in the WCH population (HR: 3.17, p = .043), but was a protective factor in the SEER population (HR: 0.8, p = .002), which might be related to the differences of HPV infection status. CONCLUSIONS: Even though differences in patient characteristics existed between the Chinese, American, and Asian American populations, our ten-year real-world data and SEER data suggested that patients with OPSCC who received SIT had a better prognosis than those who received NST.

Applying the Spatial Transmission Network to the Forecast of Infectious Diseases Across Multiple Regions.

Objective: Timely and accurate forecast of infectious diseases is essential for achieving precise prevention and control. A good forecasting method of infectious diseases should have the advantages of interpretability, feasibility, and forecasting performance. Since previous research had illustrated that the spatial transmission network (STN) showed good interpretability and feasibility, this study further explored its forecasting performance for infectious diseases across multiple regions. Meanwhile, this study also showed whether the STN could overcome the challenges of model rationality and practical needs. Methods: The construction of the STN framework involved three major steps: the spatial kluster analysis by tree edge removal (SKATER) algorithm, structure learning by dynamic Bayesian network (DBN), and parameter learning by the vector autoregressive moving average (VARMA) model. Then, we evaluated the forecasting performance of STN by comparing its accuracy with that of the mechanism models like susceptible-exposed-infectious-recovered-susceptible (SEIRS) and machine-learning algorithm like long-short-term memory (LSTM). At the same time, we assessed the robustness of forecasting performance of STN in high and low incidence seasons. The influenza-like illness (ILI) data in the Sichuan Province of China from 2010 to 2017 were used as an example for illustration. Results: The STN model revealed that ILI was likely to spread among multiple cities in Sichuan during the study period. During the whole study period, the forecasting accuracy of the STN (mean absolute percentage error [MAPE] = 31.134) was significantly better than that of the LSTM (MAPE = 41.657) and the SEIRS (MAPE = 62.039). In addition, the forecasting performance of STN was also superior to those of the other two methods in either the high incidence season (MAPE = 24.742) or the low incidence season (MAPE = 26.209), and the superiority was more obvious in the high incidence season. Conclusion: This study applied the STN to the forecast of infectious diseases across multiple regions. The results illustrated that the STN not only had good accuracy in forecasting performance but also indicated the spreading directions of infectious diseases among multiple regions to a certain extent. Therefore, the STN is a promising candidate to improve the surveillance work.

Curcumin-Mediated Sono-Photodynamic Treatment Inactivates Listeria monocytogenes via ROS-Induced Physical Disruption and Oxidative Damage.

Sono-photodynamic sterilization technology (SPDT) has become a promising non-thermal food sterilization technique because of its high penetrating power and outstanding microbicidal effects. In this study, Listeria monocytogenes (LMO) was effectively inactivated using curcumin as the sono-photosensitizer activated by ultrasound and blue LED light. The SPDT treatment at optimized conditions yielded a 4-log reduction in LMO CFU. The reactive oxygen species (ROS) production in LMO upon SPDT treatment was subsequently investigated. The results demonstrated SPDT treatment-induced excessive ROS generation led to bacterial cell deformation and membrane rupture, as revealed by the scanning electron microscope (SEM) and cytoplasmic material leakage. Moreover, agarose gel electrophoresis and SDS-PAGE further revealed that SPDT also triggered bacterial genomic DNA cleavage and protein degradation in LMO, thus inducing bacterial apoptosis-like events, such as membrane depolarization.

Public awareness, emotional reactions and human mobility in response to the COVID-19 outbreak in China - a population-based ecological study.

BACKGROUND: The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak. METHODS: We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents. RESULTS: There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th-26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5-371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%-2.3%). The epidemic phase (27th January-15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI -40.4 to -14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February-31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility. CONCLUSIONS: During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.

Evaluating the prognostic contributions of TNM classifications and building novel staging schemes for middle ear squamous cell carcinoma.

BACKGROUND: A universally acknowledged cancer staging system considering all aspects of the T-, N-, and M-classifications for middle ear squamous cell carcinoma (MESCC) remains absent, limiting the clinical management of MESCC patients. MATERIALS AND METHODS: A total of 214 MESCC patients were extracted from the SEER (the Surveillance, Epidemiology, and End Results) database between 1973 and 2016. The relationships between patient's characteristics and prognoses were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Novel staging schemes for MESCC were designed by adjusted hazard ratio (AHR) modeling method according to the combinations of Stell's T-classification and the eighth AJCC N- and M-classifications, of which performances were evaluated based on five criteria: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance. RESULTS: T-classification was the most significant prognostic factor for MESCC patients in multivariable analysis (p = 0.021). The N- and M-classifications also had obvious prognostic effect but were not statistically significant by multivariate analysis due to the limited metastasis events. Three novel staging schemes (AHR-Ⅰ-Ⅲ models, different combination of T- and N-classifications) and ST (solely derived from Stell's T-classification) were developed, among which the AHR-Ⅰ staging scheme performed best. CONCLUSIONS: Tumor extension, quantified by Stell's T-classification, is the most significant prognostic factor for MESCC patients. However, our AHR-Ⅰ staging scheme, a comprehensive staging scheme that integrating T-, N-, and M-classifications, might be an optimal option for clinical practitioners to predict MESCC patients' prognosis and make proper clinical decisions.

Spatial transmission network construction of influenza-like illness using dynamic Bayesian network and vector-autoregressive moving average model.

BACKGROUND: Although vaccination is one of the main countermeasures against influenza epidemic, it is highly essential to make informed prevention decisions to guarantee that limited vaccination resources are allocated to the places where they are most needed. Hence, one of the fundamental steps for decision making in influenza prevention is to characterize its spatio-temporal trend, especially on the key problem about how influenza transmits among adjacent places and how much impact the influenza of one place could have on its neighbors. To solve this problem while avoiding too much additional time-consuming work on data collection, this study proposed a new concept of spatio-temporal route as well as its estimation methods to construct the influenza transmission network. METHODS: The influenza-like illness (ILI) data of Sichuan province in 21 cities was collected from 2010 to 2016. A joint pattern based on the dynamic Bayesian network (DBN) model and the vector autoregressive moving average (VARMA) model was utilized to estimate the spatio-temporal routes, which were applied to the two stages of learning process respectively, namely structure learning and parameter learning. In structure learning, the first-order conditional dependencies approximation algorithm was used to generate the DBN, which could visualize the spatio-temporal routes of influenza among adjacent cities and infer which cities have impacts on others in influenza transmission. In parameter learning, the VARMA model was adopted to estimate the strength of these impacts. Finally, all the estimated spatio-temporal routes were put together to form the final influenza transmission network. RESULTS: The results showed that the period of influenza transmission cycle was longer in Western Sichuan and Chengdu Plain than that in Northeastern Sichuan, and there would be potential spatio-temporal routes of influenza from bordering provinces or municipalities into Sichuan province. Furthermore, this study also pointed out several estimated spatio-temporal routes with relatively high strength of associations, which could serve as clues of hot spot areas detection for influenza surveillance. CONCLUSIONS: This study proposed a new framework for exploring the potentially stable spatio-temporal routes between different places and measuring specific the sizes of transmission effects. It could help making timely and reliable prediction of the spatio-temporal trend of infectious diseases, and further determining the possible key areas of the next epidemic by considering their neighbors' incidence and the transmission relationships.

Clinical outcomes of different treatments and risk factors in patients with otogenic brain abscess, a real-world evidence-based retrospective study.

BACKGROUND: Otogenic Brain Abscess (OBA) is a life-threatening complication secondary to otitis media, but its appropriate management remains controversial. OBJECTIVES: To understand the demographic characteristics, management, and variables that affect the outcomes of patients with OBA based on our experiences over 11 years. MATERIAL AND METHODS: Clinical data were collected for 41 patients. Prognostic factors associated with mortality were assessed, and clinical outcomes compared among groups receiving different treatments. RESULTS: Among the 41 patients, 19.6% did not undergo surgery, 39.0% were treated with two-stage surgery (otological surgery and neurosurgery) and 41.4% were treated with single-stage surgery (otological surgery or neurosurgery). Overall mortality rate was 32.5%, and mortality was significantly higher in patients with invasion of the petrous apex (odds ratio [OR]: 7.81, 95% confidence interval [95% CI]: 1.26-48.36), and lower in those with appropriate surgical management (single otological surgery, OR: 0.07, 95% CI: 0-0.97; single neurosurgery, OR: 0.13, 95% CI: 0.02-1.0; two-stage surgery, OR: 0.08, 95% CI: 0.01-0.64) or a higher Glasgow Coma Scale (GCS) score at admission (OR: 0.64, 95% CI: 0.44-0.93). CONCLUSIONS AND SIGNIFICANCE: Data on invasiveness and pre-surgery GCS greatly aid in predicting the prognosis of OBA patients. Early evaluation will facilitate decision-making by physicians treating OBA patients.

The effect of dealuminated jellyfish in mitigating toxicity on mice exposed to aluminum.

In the present study, the removal effect of dealuminated jellyfish on Aluminum (Al) in mice was evaluated. The results showed that the consumption of dealuminated jellyfish significantly decreased Al accumulation in the liver of mice, indicating an Al-removing effect of dealuminated jellyfish on Al-enriched mice. In addition, the effect of dealuminated jellyfish consumption on an Al-overload model was further evaluated. The result showed that the Al content in different tissues and organs of mice was significantly reduced, but it had no significant effect on the other metallic element content. These results indicated that the samples from oral administration have a certain Al-removing effect in Al-overloaded mice. Moreover, the cluster analysis of differentially expressed proteins in blood and liver showed that a high dose of dealuminated jellyfish improve the expression of amine oxidase B and enhance the effect of Al discharge.