Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunotherapy resistance in esophageal cancer: Possible mechanisms and clinical implications

Esophageal cancer (EC) is a common malignant gastrointestinal (GI) cancer in adults. Although surgical technology combined with neoadjuvant chemoradiotherapy has advanced rapidly, patients with EC are often diagnosed at an advanced stage and the five-year survival rate remains unsatisfactory. The poor prognosis and high mortality in patients with EC indicate that effective and validated therapy is of great necessity. Recently, immunotherapy has been successfully used in the clinic as a novel therapy for treating solid tumors, bringing new hope to cancer patients. Several immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell therapy, and tumor vaccines, have achieved significant breakthroughs in EC treatment. However, the overall response rate (ORR) of immunotherapy in patients with EC is lower than 30%, and most patients initially treated with immunotherapy are likely to develop acquired resistance (AR) over time. Immunosuppression greatly weakens the durability and efficiency of immunotherapy. Because of the heterogeneity within the immune microenvironment and the highly disparate oncological characteristics in different EC individuals, the exact mechanism of immunotherapy resistance in EC remains elusive. In this review, we provide an overview of immunotherapy resistance in EC, mainly focusing on current immunotherapies and potential molecular mechanisms underlying immunosuppression and drug resistance in immunotherapy. Additionally, we discuss prospective biomarkers and novel methods for enhancing the effect of immunotherapy to provide a clear insight into EC immunotherapy.
Functions of regulators of G protein signaling 16 in immunity, inflammation, and other diseases

Regulators of G protein signaling (RGS) act as guanosine triphosphatase activating proteins to accelerate guanosine triphosphate hydrolysis of the G protein α subunit, leading to the termination of the G protein-coupled receptor (GPCR) downstream signaling pathway. RGS16, which is expressed in a number of cells and tissues, belongs to one of the small B/R4 subfamilies of RGS proteins and consists of a conserved RGS structural domain with short, disordered amino- and carboxy-terminal extensions and an α-helix that classically binds and de-activates heterotrimeric G proteins. However, with the deepening of research, it has been revealed that RGS16 protein not only regulates the classical GPCR pathway, but also affects immune, inflammatory, tumor and metabolic processes through other signaling pathways including the mitogen-activated protein kinase, phosphoinositide 3-kinase/protein kinase B, Ras homolog family member A and stromal cell-derived factor 1/C-X-C motif chemokine receptor 4 pathways. Additionally, the RGS16 protein may be involved in the Hepatitis B Virus -induced inflammatory response. Therefore, given the continuous expansion of knowledge regarding its role and mechanism, the structure, characteristics, regulatory mechanisms and known functions of the small RGS proteinRGS16 are reviewed in this paper to prepare for diagnosis, treatment, and prognostic evaluation of different diseases such as inflammation, tumor, and metabolic disorders and to better study its function in other diseases.
Reporting the accuracy of small-scale fishing data by simply applying Benford’s law

Small-scale fisheries (SSFs) play essential economic, social, and cultural roles for many fleets in the Atlantic region. The basis of fisheries assessment and management is the landings reported by observers or fishers. Even though the information from the landings is essential, it can be subject to a fisher’s bias, such as the tendency to inflate catches and the refusal to fill the logs. The feasibility for managers using field surveys to validate these datasets is held up by the high costs, shortage in monitoring, and the lack of prior information. Alternatively, Benford analysis overcomes those limitations since it can be applied directly on the logbook data. This method is growing in popularity, underlining its suitability to many economic and biological fields. Hence, in this study, we inspected small-scale fisheries data by the Benford’s distribution, aiming to validate fish landing data from 27 points in Brazil’s northeastern region over 3 years. Our results suggest that 20% of landings data are considered highly imprecise (misinformation), especially from non-motorized canoes. Also, harbors in remote locations provide poorer quality data, specifically monthly catch values reported by several boats. The way we mine our data affects the sensitivity of the analysis, with monthly data being less prone to be accessed by this method than daily information. As the results match our prior knowledge on the location, we endorse the suitability of the method and reliability for assessing accuracy in fishing data. Hence, we recommend that it ought to be used as an audit tool for SSF landing data aiming to enlighten data reliance and support managers for planning management actions.
Rhodotorula benthica culture as an alternative to antibiotics improves growth performance by improving nutrients digestibility and intestinal morphology, and modulating gut microbiota of weaned piglets

The effects of Rhodotorula benthica culture (RBC) and antibiotics (AB) on the growth performance, nutrients digestibility, morphological indicators, and colonic microbiota of weaning piglets were explored. Ninety-six (Duroc × Landrace × Large) weaned piglets (21-day-old) weighing 7.7 ± 0.83 kg, were randomly allocated to 4 dietary treatments. They were fed with basal diet (CON), basal diet + 25 mg/kg bacitracin zinc + 5 mg/kg colistin sulfate (AB), 5 g/kg reduction in soybean meal of basal diet + 5 g/kg RBC (RBC1), or 10 g/kg reduction in soybean meal of basal diet + 10 g/kg RBC (RBC2). The results showed that dietary RBC1 improved the body gain/feed intake (G/F) of weaned piglets than the CON diet, and the RBC2 diet improved the average daily gain and G/F than CON and AB diets from days 15 to 28 (P < 0.05). Supplementation of RBC2 improved the apparent total tract digestibility of dry matter, nitrogen, and gross energy in weaned piglets compared to controls from days 15 to 28 (P < 0.05). Dietary AB, RBC1, and RBC2 enhanced the ileal villus height (VH) and VH/crypt depth (CD), and these two indicators were greater in the RBC2-treated piglets than in the AB- and RBC1-treated piglets (P < 0.05). The activity of serum superoxide dismutase (SOD) was enhanced by dietary AB, RBC1, and RBC2 (P < 0.05). Serum glutathione (GSH) concentration was elevated by dietary RBC1 and RBC2 (P < 0.05). According to 16S rRNA sequence analysis, AB- and RBC2-treated piglets had a higher relative abundance of Firmicutes and Lachnospiraceae in the colon digesta, and more abundant Lactobacillus was found in RBC1-treated piglets, as compared to the CON group. Additionally, RBC2 supplementation increased the α diversity [Chao1, PD-whole-tree, and observed operational taxonomic units (OTUs)] compared to the CON group. Taken together, the dietary RBC improved the growth performance of weaned piglets. In addition, 10 g/kg of RBC2 in the diet achieved better effects on higher ADG, ileal villi morphology, and stronger antioxidant capacity than dietary AB and RBC1 in weaning piglets.
Evaluating the stock status of 10 croaker species landed along the north-eastern Arabian Sea using the length-based Bayesian biomass approach

India accounts for nearly 60% of the croakers caught in the Indian Ocean. The north-west (NW) coast of India is the most productive fishing ground for croakers and contributes almost half of the nation’s croaker catch. Lesser sciaenids (small- and medium-sized croakers) are the multi-species complex landed by commercial trawlers along the NW coast of India. Despite several notable changes in the fishing pattern in the region, such as the emergence of multi-day fishing and increasing dominance of pelagic trawling, there is no recent assessment of this major demersal fishery group. The present study evaluates the stock status of 10 species of lesser sciaenids forming the commercial fishery in the region using length frequency data collected during 2020–2021. The assessment was made using the length-based Bayesian biomass (LBB) estimation method. The indicators of relative biomass (B/B0 and B/BMSY) showed that most of the species (seven) are fully exploited, whereas two and one species were found under- and over-exploited, respectively. Excessive juveniles (Lmean/Lopt and Lc/Lc_opt< 0.90) in catches were observed in the case of Paranibea semiluctuosa. A sufficient number of larger individuals (L95th/Linf< 0.90) in the population were lacking in the case of Johnius belangerii and Otoithes ruber. However, the study indicated a gradual improvement in stock status for most of the species over previous estimates, which can be attributed to the diversion of trawl fishing efforts towards the pelagic realm.
A moderated mediation mechanism underlying the impact of website telepresence on purchase intention — Evidence from Chinese female college student customers

Telepresence in e-commerce, the feeling of resembling shopping in a physical store, plays a critical role in determining online purchase intention. However, the cognitive mechanism and boundary conditions about its effect still need further investigation. The current study construed flow experience and socioeconomic status as important variables and developed a moderated mediation model for their roles in the effect of telepresence. The model was supported by our study where a group of Chinese female college students participated in simulated online apparel shopping and completes relevant questionnaire surveys. The results show that: (1) website telepresence predicts positively the purchase intention of females, (2) flow experience mediates the impact of website telepresence on purchase intention, and (3) the relationship between website telepresence and flow experience could be moderated by socioeconomic status, namely, females with higher socioeconomic status demonstrate stronger mediation of flow experience. These findings can help researchers and online retailers understand the flow concept in e-commerce and formulate marketing strategies to retain consumers with different socioeconomic statuses.
Gibberellic acid promotes selenium accumulation in Cyphomandra betacea under selenium stress

The selenium (Se) deficiency is threatening the human health, and the increase of Se content in food can prevent the Se deficiency of human body. To increase the Se content in fruit trees and alleviate the Se stress to fruit trees, the effects of gibberellic acid (GA) on the growth and Se accumulation in Cyphomandra betacea under Se stress were studied. Although GA increased the biomass of C. betacea, it did not significantly affect the root/shoot ratio. The root and shoot biomass had a quadratic polynomial regression relationship with the GA concentration. Furthermore, GA increased the photosynthetic pigment content, photosynthetic parameters, and antioxidant enzyme activity of C. betacea. GA also increased the Se content in C. betacea, peaking at 300 mg/L GA. For instance, GA (300 mg/L) increased the Se contents in roots and shoots of C. betacea by 70.31 and 22.02%, respectively, compared with the control. Moreover, the root Se and shoot Se contents had a quadratic polynomial regression relationship with the GA concentration. Correlation and gray relational analyses showed that the carotenoid, chlorophyll a, and chlorophyll b contents were closely related to the Se uptake in C. betacea under the GA application. These results show that GA (300 mg/L) can promote the growth and Se uptake of C. betacea under Se stress.
Proton-induced DNA damage promotes integration of foreign plasmid DNA into human genome

High-risk human papillomaviruses (HPVs) cause virtually all cervical cancer cases and are also associated with other types of anogenital and oropharyngeal cancers. Normally, HPV exists as a circular episomal DNA in the infected cell. However, in some instances, it integrates into the human genome in such a way as to enable increased expression of viral oncogenes, thereby leading to carcinogenesis. Since viral integration requires breaks in both viral and human genomes, DNA damage likely plays a key role in this critical process. One potentially significant source of DNA damage is exposure to elevated doses of ionizing radiation. Natural background radiation is ubiquitous; however, some populations, including radiological workers, radiotherapy patients, and astronauts, are exposed to significantly higher radiation doses, as well as to different types of radiation such as particle radiation. We hypothesize that ionizing radiation-induced DNA damage facilitates the integration of HPV into the human genome, increasing the risk of developing HPV-related cancers in the exposed population. To test this, we first determined the kinetics of DNA damage in keratinocytes exposed to ionizing radiation (protons) by assessing γ-H2AX foci formation using immunofluorescence (direct damage), and also measured ROS and 8-oxoG levels via DCFDA and Avidin-FITC (indirect damage). As anticipated, direct DNA damage was observed promptly, within 30 min, whereas indirect DNA damage was delayed due to the time required for ROS to accumulate and cause oxidative damage. Although radiation was lethal at high doses, we were able to establish an experimental system where radiation exposure (protons and X-rays) induced DNA damage dose-dependently without causing major cytotoxic effects as assessed by several cytotoxicity assays. Most importantly, we explored the impact of radiation exposure on integration frequency using a clonogenic assay and demonstrated that as predicted, proton-induced DNA damage promotes the integration of HPV-like foreign DNA in oral keratinocytes. Overall, the insights gained from this work enable us to better understand the contribution of radiation exposure and DNA damage to HPV-mediated carcinogenesis and direct us toward strategies aimed at preventing malignancies in HPV-infected individuals.
Real-world clinical treatment outcomes in Chinese non-small cell lung cancer with EGFR exon 20 insertion mutations

Background EGFR exon 20 insertions (EGFR ex20ins) constitute a heterogeneous subset of EGFR-activating alterations. However, the effectiveness of standard therapy in patients with EGFR ex20ins remains poor. Methods In our study, we retrospectively collected next-generation sequencing (NGS) data from 7,831 Chinese NSCLC patients and analyzed the relationship between EGFR ex20ins variations and medical records. Results Our data showed that EGFR ex20ins account for up to 3.5% of all EGFR mutation non-small-cell lung cancer (NSCLC) patients and 1.6% of all NSCLC patients in China. Thirty-eight different variants of EGFR ex20ins were identified in 129 NSCLC patients. We observed that the patients with EGFR ex20ins may benefit from the anti-angiogenesis agents significantly (P = 0.027). In the EGFR ex20ins near-loop group, patients who received second-/third-generation EGFR-TKI therapy treatment as first-line treatment had a longer median progression-free survival (PFS) than those who initiated treatment with first-generation EGFR-TKI or chemotherapy. Patients with co-mutations of EGFR ex20ins near-loop and TP53 tended to have a shorter OS in second-/third-generation EGFR-TKI therapy (P = 0.039). Additionally, median PFS was significantly longer in patients harboring EGFR ex20ins far-loop variants who received chemotherapy as a first-line setting (P = 0.037). Conclusions Overall survival was significantly longer in EGFR ex20ins patients with anti-angiogenesis agents. For the choice of first-line strategy, NSCLC with EGFR ex20ins near-loop variants may benefit from second-/third-generation EGFR-TKI, while patients harboring EGFR ex20ins far-loop variants might have better outcomes from chemotherapy. TP53 could serve as a potential predictive marker in poor prognosis for EGFR ex20ins near-loop patients.
The research progress of targeted therapy in acute myeloid leukemia based on bibliometric analysis

COPYRIGHT © 2022 Huang, Sun, Wang and Long. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author (s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Review PUBLISHED 02 September 2022 DOI 10.3389/fonc.2022. 957370
SARS-CoV-2 vaccination in androgen sensitive phenotypes – A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients

Background Androgen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection. Purpose We aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH. Method We collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of anti-androgen therapy. Result A total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p < 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p < 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019). Conclusion Co-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes.
β1-Integrin plays a major role in resveratrol-mediated anti-invasion effects in the CRC microenvironment

Graphical Abstract Background: Tumor microenvironment (TME) is one of the most important factors in tumor aggressiveness, with an active exchange between tumor and other TME-associated cells that promotes metastasis. The tumor-inhibitory effect of resveratrol on colorectal cancer (CRC) cells has been frequently reported. However, whether resveratrol can specifically suppress TME-induced CRC invasion via β1-integrin receptors has not been fully elucidated yet. Methods: Two CRC cell lines (HCT116, RKO) were cultured in multicellular, pro-inflammatory 3D-alginate TME cultures (containing fibroblasts, T-lymphocytes) to investigate the role of β1-integrin receptors in the anti-invasive and anti-metastatic effect of resveratrol by antisense oligonucleotides (ASO). Results: Our results show that resveratrol dose-dependently suppressed the migration-promoting adhesion adapter protein paxillin and simultaneously enhanced the expression of E-cadherin associated with the phenotype change of CRC cells, and their invasion. Moreover, resveratrol blocked TME-induced phosphorylation and nuclear translocation of p65-NF-κB, which was associated with changes in the expression pattern of epithelial-mesenchymal-transition-related biomarkers (slug, vimentin, E-cadherin), metastasis-related factors (CXCR4, MMP-9, FAK), and apoptosis (caspase-3). Finally, transient transfection of β1-integrin, in contrast to knockdown of NF-κB, abrogated most anti-invasive, anti-metastatic effects as well as downstream signaling of resveratrol, resulting in a concomitant increase in CRC cell invasion, indicating a central role of β1-integrin receptors in the anti-invasive function of resveratrol. Conclusion: These results demonstrate for the first time that silencing β1-integrins may suppress, at least in part the inhibitory effects of resveratrol on invasion and migration of CRC cells, underscoring the crucial homeostatic role of β1-integrin receptors.
Investigating the physiological response and antibody concentration of gilthead sea bream (Sparus aurata) following Vibrio anguillarum vaccination depending on the stress coping style

Stress coping styles (SCSs) are defined as coherent sets of individual physiological and behavioral differences in stress response consistent across time and context and are described in a wide range of taxa, including fishes. These differences in behavior and physiology are of great interest because they may have direct implications on animal health, welfare, and performance in farming systems, including aquaculture. In this study, the physiological responses of sea bream (Sparus aurata) from different SCSs following Vibrio anguillarum vaccination were monitored. Fish were first screened either bold or shy (proxy of proactive and reactive SCSs, respectively) using group risk-taking tests and were then injected with a vaccine against V. anguillarum. Following vaccination, the fish were implanted with an accelerometer tag to monitor their swimming activity (proxy of energy expenditure), and blood sampling was carried out to measure health and welfare parameters (e.g., cortisol, glucose, hemoglobin) and aspecific immunity (e.g., protease, total proteins). In addition, blood was also collected at three different sampling times to screen antibody levels and, thus, to evaluate the efficiency of the vaccine. Following vaccination, bold fish displayed lower swimming activity values, indicative of lower energy expenditure, and also displayed higher levels of hematocrit, total proteins, and lysozyme in the plasma than the shy ones, which could be indicative of better health/welfare status and greater aspecific immunity. Finally, the V. anguillarum vaccination appeared to be more efficient in bold fish since the number of total antibodies was found higher than in shy fish 1 month after vaccination. Such results could help improve both health/welfare and productivity of farmed sea breams by selecting more robust fish, better adapted to farming conditions.