Node-sparing modified short-course Radiotherapy Combined with CAPOX and Tislelizumab for locally Advanced MSS of Middle and low rectal Cancer (mRCAT): an open-label, single-arm, prospective, multicentre clinical trial.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. METHODS: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. DISCUSSION: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. TRIAL REGISTRATION: This study was registered at www. CLINICALTRIALS: gov . TRIAL REGISTRATION NUMBER: NCT05972655. Date of registration: 31 July 2023.

Development and validation of a prediction model for suboptimal ovarian response in polycystic ovary syndrome (PCOS) patients undergoing GnRH-antagonist protocol in IVF/ICSI cycles.

BACKGROUND: PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients. METHODS: This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model. RESULTS: The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157-0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability. CONCLUSION: The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment.

Identification and prognostic analysis of candidate biomarkers for lung metastasis in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent types of malignant tumors. It's vital to explore new biomarkers and potential therapeutic targets in CRC lung metastasis through adopting integrated bioinformatics tools. Multiple cohort datasets and databases were integrated to clarify and verify potential key candidate biomarkers and signal transduction pathways in CRC lung metastasis. DAVID, STRING, UALCAN, GEPIA, TIMER, cBioPortal, THE HUMAN PROTEIN ATLAS, GSEA 4.3.2, FUNRICH 3.1.3, and R 4.2.3 were utilized in this study. The enriched biological processes and pathways modulated by the differentially expressed genes (DEGs) were determined with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. The search tool Retrieval of Interacting Genes and Cytoscape were used to construct a protein-protein interaction network among DEGs. Four hundred fifty-nine colorectal primary cancer and lung metastatic gene expression profiles were screened from 3 gene expression profiles (GSE41258, GSE68468, and GSE41568). Forty-one upregulated genes and 8 downregulated genes were identified from these 3 gene expression profiles and verified by the transcriptional levels of hub genes in other GEO datasets and The Cancer Genome Atlas database. Two pathways (immune responses and chemokine receptors bind chemokines), 13 key DEGs, 6 hub genes (MMP3, SFTPD, ABCA3, CLU, APOE, and SPP1), and 2 biomarkers (APOE, SPP1) with significantly prognostic values were screened. Forty-nine DEGs were identified as potential candidate diagnostic biomarkers for patients with CRC lung metastasis in present study. Enrichment analysis indicated that immune responses and chemokine receptors bind chemokines may play a leading role in lung metastasis of CRC, and further studies are needed to validate these findings.

A multicenter clinical AI system study for detection and diagnosis of focal liver lesions.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer.

Although the role of T cells in tumor immunity and modulation of the tumor microenvironment (TME) has been extensively studied, their precise involvement in gastric adenocarcinoma remains inadequately explored. In this work, we analyzed the single-cell RNA sequencing data set in GSE183904 and identified 322 T cell marker genes using the "FindAllMarkers" method of the R package "Seurat". STAD patients in the TCGA database were divided into high-risk and low-risk categories based on risk scores. The five-gene prediction signature based on T cell marker genes can predict the prognosis of gastric cancer patients with high accuracy. In the training cohort, the areas under the receiver operating characteristic (ROC) curve were 0.667, 0.73, and 0.818 at 1, 3, and 5 years. External validation of the predictive signature was also performed using multiple clinical subgroups and GEO cohorts. To help with practical application, a diagnostic model was created that shows values of 0.732, 0.752, and 0.816 for the relevant areas under the ROC curve at 1, 3, and 5 years. The T cell marker genes identified in this study may serve as potential therapeutic targets, and the developed predictive signatures and nomograms may aid in the clinical management of gastric cancer.

Influence of hypoxia on retinal progenitor and ganglion cells in human induced pluripotent stem cell-derived retinal organoids.

AIM: To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs). METHODS: The hiPSC and a three-dimensional culture method were used for the experiments. Generated embryoid bodies (EBs) were randomly and equally divided into hypoxic and normoxic groups. Photographs of the EBs were taken on days 38, 45, and 52, and the corresponding volume of EBs was calculated. Simultaneously, samples were collected at these three timepoints, followed by fixation, sectioning, and immunofluorescence. RESULTS: The proportion of Ki67-positive proliferating cells increased steadily on day 38; this proliferation-promoting effect tended to increase tissue density rather than tissue volume. On days 45 and 52, the two groups had relatively similar ratios of Ki67-positive cells. Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52 (P<0.05). In contrast, the percentage of PAX6- and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints (P<0.01), except for CHX10 at day 45 (P>0.05). Moreover, the proportion of PAX6-/TUJ1+ cells within the neural retinas increased considerably (P<0.01, <0.05, <0.05 respectively). CONCLUSION: Low oxygen promotes stemness and proliferation of neural retinas, suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.

Association between hypertension and Epstein-Barr virus reactivation among the population in a high-risk area for nasopharyngeal carcinoma.

BACKGROUND: Hypertension may increase the infection risk of multiple viruses. The evidence for the association between hypertension and Epstein-Barr virus (EBV) reactivation is still largely lacking. METHODS: The study was based on the baseline information of a population-based prospective cohort from high-risk areas of nasopharyngeal carcinoma (NPC). Using two EBV reactivation classification criteria, we explored the relationship between hypertension and EBV reactivation through logistic regression models. RESULTS: We included a total of 12,159 subjects. Among them, 3,945 (32.45%) were EBV arbitrary seropositive, and 1,547 (12.72%) were EBV comprehensive seropositive. Hypertension was associated with an increased risk of EBV reactivation, with odds ratios (ORs) of 1.17 (95% CI = 1.08-1.27) for EBV arbitrary seropositive subjects and 1.16 (95% CI = 1.03-1.30) for EBV comprehensive seropositive subjects. Two types of antihypertensive drugs were associated with decreased risk of EBV reactivation: ß-adrenergic receptor-blocking agents (ß-blockers) (OR = 0.51, 95% CI = 0.42-0.61 for EBV arbitrary seropositive subjects; OR = 0.62, 95% CI = 0.47-0.81 for EBV comprehensive seropositive subjects) and angiotensin converting enzyme inhibitors (ACEIs) (OR = 0.61, 95% CI = 0.41-0.88 for EBV arbitrary seropositive subjects; OR = 0.58, 95% CI = 0.32-0.98 for EBV comprehensive seropositive subjects). CONCLUSIONS: Hypertension was associated with an increased risk of EBV reactivation in high-incidence areas of NPC. ß-blockers and ACEIs reduce this risk, and thus might be used for NPC prevention in endemic areas.

Protective effects of resveratrol on the ethanol-induced disruption of retinogenesis in pluripotent stem cell-derived organoids.

Prenatal alcohol exposure-induced fetal alcohol syndrome (FAS) can lead to serious maldevelopment in many organ systems, including the eyes. In the present study, the effects of alcohol exposure on early development of the human retina and the therapeutic effects of resveratrol on alcohol-induced neural retinal damage were observed for the first time in an in vitro retinal organoid model. We report that the number of proliferating and apoptotic cells decreased and increased, respectively, following ethanol treatment. In addition, the number of PAX6+ cells and migrating TUJ1+ cells decreased after ethanol exposure. However, pretreatment with resveratrol prevented all of these negative effects. Using RNA sequencing and immunofluorescence, we identified activation of the PI3K-AKT signalling pathway as the possible mechanism through which resveratrol protects the retina from alcohol-induced damage. These results suggest that while ethanol exposure can restrict the growth of the human retina and impede the development of specific retinal cells, pretreatment with resveratrol may be a feasible method for preventing these effects.

Analysis of spatial-temporal dynamic distribution and related factors of tuberculosis in China from 2008 to 2018.

Through spatial-temporal scanning statistics, the spatial-temporal dynamic distribution of pulmonary tuberculosis incidence in 31 provinces and autonomous regions of China from 2008 to 2018 is obtained, and the related factors of spatial-temporal aggregation of tuberculosis in China are analyzed to provide strong scientific basis and data support for the prevention and control of pulmonary tuberculosis. This is a retrospective study, using spatial epidemiological methods to reveal the spatial-temporal clustering distribution characteristics of China's tuberculosis epidemic from 2008 to 2018, in which cases data comes from the China Center for Disease Control and prevention. Office Excel is used for general statistical description, and the single factor correlation analysis adopts χ2 Test (or trend χ2 Inspection). Retrospective discrete Poisson distribution space time scanning statistics of SaTScan 9.6 software are used to analyze the space time dynamic distribution of tuberculosis incidence in 31 provinces, cities and autonomous regions in China from 2008 to 2018. ArcGIS 10.2 software is used to visualize the results. The global spatial autocorrelation analysis adopts Moran's I of ArcGIS Map(Monte Carlo randomization simulation times of 999) is used to analyze high-risk areas, low-risk areas and high-low risk areas. From 2008 to 2018, 10,295,212 cases of pulmonary tuberculosis were reported in China, with an average annual incidence rate of 69.29/100,000 (95% CI: (69.29 ± 9.16)/100,000). The annual GDP (gross domestic product) of each province and city showed an upward trend year by year, and the number of annual medical institutions in each province and city showed a sharp increase in 2009, and then tended to be stable; From 2008 to 2018, the national spatiotemporal scanning statistics scanned a total of 6 clusters, including 23 provinces and cities. The national high-low spatiotemporal scanning statistics of the number of pulmonary tuberculosis cases scanned a total of 2 high-risk and low-risk clusters. The high-risk cluster included 8 provinces and cities, and the low-risk cluster included 12 provinces and cities. The global autocorrelation Moran's I index of the incidence rate of pulmonary tuberculosis in all provinces and cities was greater than the expected value (E (I) = -0.0333); The correlation analysis between the average annual GDP and the number of pulmonary tuberculosis cases in each province and city from 2008 to 2018 was statistically significant. From 2008 to 2018, the spatial and temporal scanning and statistical scanning areas of tuberculosis incidence in China were mainly concentrated in the northwest and southern regions of China. There is an obvious positive spatial correlation between the annual GDP distribution of each province and city, and the aggregation degree of the development level of each province and city is increasing year by year. There is a correlation between the average annual GDP of each province and the number of tuberculosis cases in the cluster area. There is no correlation between the number of medical institutions set up in each province and city and the number of pulmonary tuberculosis cases.

Impacts of autophagy on the formation of organelle-free zone during the lens development.

The thorough degeneration of organelles in the core of the lens is certainly a hallmark event during the lens development. Organelles degradation in the terminal differentiation process of lens fiber cells to form an organelle-free zone is critical for lens maturation and transparency. Several mechanisms have been proposed to expand our understanding of lens organelles degradation, including apoptotic pathways, the participation of ribozyme, proteolytic enzyme and phospholipase A and acyltransferase, and the newly discovered roles for autophagy. Autophagy is a lysosome-dependent degradation reaction during which the "useless" cellular components are degraded and recycled. These cellular components, such as incorrectly folded proteins, damaged organelles and other macromolecules, are first engulfed by the autophagosome before being further delivered to lysosomes for degradation. Although autophagy has been recognized involving in organelle degradation of the lens, the detailed functions remain to be discovered. Recent advances have revealed that autophagy not only plays a vital role in the intracellular quality control of the lens but is also involved in the degradation of nonnuclear organelles in the process of lens fiber cell differentiation. Herein, we first review the potential mechanisms of organelle-free zone formation, then discuss the roles of autophagy in intracellular quality control and cataract formation, and finally substantially summarize the potential involvement of autophagy in the development of organelle-free zone formation.

The impact of age on outcomes of breast cancer in different hormone receptor and HER2 groups.

OBJECTIVE: The aim of the current study was to explore the association between age and outcomes in breast cancer. METHODS: Patients during 2010-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and breast cancer-specific death (BCSD) were taken as endpoints. The restrict cubic spline graph (RCS) was used to explore the relationship between age and outcomes in patients, and the cumulative incidence of BCSD and non-BCSD was calculated using the Gray method. Age-specific gene expression profiles were studied using RNA sequence data from the Cancer Genome Atlas (TCGA) database to explore whether there were young age-related gene or gene sets. RESULTS: A total of 142,755 patients with breast cancer were included. The hazard ratio (HR) of OS for Patients with stage I-III breast cancer was roughly stable before 53 years old and increased significantly after that, and the HR of BCSD for these patients showed a U-shaped distribution when plotted against age, with patients younger than 50 years and patients older than 70 years experiencing the worst survival. Further stratified analysis according to molecular subtype revealed that the U-shaped distribution of the HR of BCSD with was only found in the Hormone receptor-positive/HER2-negative (HoR+/HER2-) subgroup. The cumulative incidence plots showed that young age was associated with worse BCSD in the breast cancer patients with stage I-III and HoR+/HER2- subgroup. In stage IV breast cancer, there was a linearity of the relationship between poor OS and increasing age. We failed to find any differentially expressed age-specific genes between 20-40 years and 41-60 years groups in 258 patients with stage I-III and HoR+/HER2- subtype. CONCLUSION: Young age could predict worse BCSD of patient with stage I-III and HoR+/HER2- breast cancer. The escalating therapy was recommended to young age breast cancer with stage I-III and HoR+/HER2- subtype.

Multi-omics Analysis of the Role of PHGDH in Colon Cancer.

Objectives: Serine metabolism is essential for tumor cells. Endogenous serine arises from de novo synthesis pathways. As the rate-limiting enzyme of this pathway, PHGDH is highly expressed in a variety of tumors including colon cancer. Therefore, targeted inhibition of PHGDH is an important strategy for anti-tumor therapy research. However, the specific gene expression and metabolic pathways regulated by PHGDH in colon cancer are still unclear. Our study was aimed to clarified the role of PHGDH in serine metabolism in colon cancer to provide new knowledge for in-depth understanding of serine metabolism and PHGDH function in colon cancer. Methods: In this study, we analyzed the gene expression and metabolic remodeling process of colon cancer cells (SW620) after targeted inhibition of PHGDH by gene transcriptomics and metabolomics. LC-MS analysis was performed in 293T cells to PHGDH gene transcription and protein post-translational modification under depriving exogenous serine. Results: We found that amino acid transporters, amino acid metabolism, lipid synthesis related pathways compensation and other processes are involved in the response process after PHGDH inhibition. And ATF4 mediated the transcriptional expression of PHGDH under exogenous serine deficiency conditions. While LC-MS analysis of post-translational modification revealed that PHGDH produced changes in acetylation sites after serine deprivation that the K289 site was lost, and a new acetylation site K21was produced. Conclusion: Our study performed transcriptomic and metabolomic analysis by inhibiting PHGDH, thus clarifying the role of PHGDH in gene transcription and metabolism in colon cancer cells. The mechanism of high PHGDH expression in colon cancer cells and the acetylation modification that occurs in PHGDH protein were also clarified by serine deprivation. In our study, the role of PHGDH in serine metabolism in colon cancer was clarified by multi-omics analysis to provide new knowledge for in-depth understanding of serine metabolism and PHGDH function in colon cancer.

Differentially expressed gene profiles and associated ceRNA network in ATG7-Deficient lens epithelial cells under oxidative stress.

Oxidation is an essential factor during cataract development. Autophagy, usually a cytoprotective process, is always found elevated in lens epithelial cells under oxidation, yet its roles and associated molecular mechanisms under such circumstances are rarely elucidated. Herein, we extracted and re-analyzed the RNA sequencing data of the GSE161701 dataset from the Gene Expression Omnibus database to identify the differentially expressed mRNAs and lncRNAs by using the R package "DESeq2". Further analyses of gene ontology and KEGG enrichment were implemented via the packages "clusterProfiler" and "enrichplot". We found that after the knockout of ATG7, differentially expressed genes were more associated with hemopoiesis, vasculature development, axonogenesis, and hypoxia regulation. When stimulated with H2O2, LECs displayed a gene expression profile correlating with apoptotic and proliferative pathways, such as the MAPK signaling pathway and FoxO signaling pathway. The differentially expressed gene profiles of the two types of LECs (wild type and ATG7 deficient) under oxidation were distinct to a large extent. Furthermore, 1,341 up-regulated and 1912 down-regulated differential mRNAs and 263 up-regulated and 336 down-regulated differential lncRNAs between these two types of LECs subjected to H2O2 were detected, among which 292 mRNAs and 24 lncRNAs possibly interacted with ten cataract-related miRNAs. A competing endogenous lncRNA-miRNA-mRNA network based on such interactions was finally constructed.

Resistin Promotes Nasopharyngeal Carcinoma Metastasis through TLR4-Mediated Activation of p38 MAPK/NF-κB Signaling Pathway.

NPC is a type of malignant tumor with a high risk of local invasion and early distant metastasis. Resistin is an inflammatory cytokine that is predominantly produced from the immunocytes in humans. Accumulating evidence has suggested a clinical association of circulating resistin with the risk of tumorigenesis and a relationship between blood resistin levels and the risk of cancer metastasis. In this study, we explored the blood levels and the role of resistin in NPC. High resistin levels in NPC patients were positively associated with lymph node metastasis, and resistin promoted the migration and invasion of NPC cells in vitro. These findings were also replicated in a mouse model of NPC tumor metastasis. We identified TLR4 as a functional receptor in mediating the pro-migratory effects of resistin in NPC cells. Furthermore, p38 MAPK and NF-κB were intracellular effectors that mediated resistin-induced EMT. Taken together, our results suggest that resistin promotes NPC metastasis by activating the TLR4/p38 MAPK/NF-κB signaling pathways.

Monitoring European data with prospective space-time scan statistics: predicting and evaluating emerging clusters of COVID-19 in European countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic infectious disease and become a serious public health crisis. As the COVID-19 pandemic continues to spread, it is of vital importance to detect COVID-19 clusters to better distribute resources and optimizing measures. This study helps the surveillance of the COVID-19 pandemic and discovers major space-time clusters of reported cases in European countries. Prospective space-time scan statistics are particularly valuable because it has detected active and emerging COVID-19 clusters. It can prompt public health decision makers when and where to improve targeted interventions, testing locations, and necessary isolation measures, and the allocation of medical resources to reduce further spread. METHODS: Using the daily case data of various countries provided by the European Centers for Disease Control and Prevention, we used SaTScan™ 9.6 to conduct a prospective space-time scan statistics analysis. We detected statistically significant space-time clusters of COVID-19 at the European country level between March 1st to October 2nd, 2020 and March 1st to October 2nd, 2021. Using ArcGIS to draw the spatial distribution map of COVID-19 in Europe, showing the emerging clusters that appeared at the end of our study period detected by Poisson prospective space-time scan statistics. RESULTS: The results show that among the 49 countries studied, the regions with the largest number of reported cases of COVID-19 are Western Europe, Central Europe, and Eastern Europe. Among the 49 countries studied, the country with the largest cumulative number of reported cases is the United Kingdom, followed by Russia, Turkey, France, and Spain. The country (or region) with the lowest cumulative number of reported cases is the Faroe Islands. We discovered 9 emerging clusters, including 21 risky countries. CONCLUSION: This result can provide timely information to national public health decision makers. For example, a country needs to improve the allocation of medical resources and epidemic detection points, or a country needs to strengthen entry and exit testing, or a country needs to strengthen the implementation of protective isolation measures. As the data is updated daily, new data can be re-analyzed to achieve real-time monitoring of COVID-19 in Europe. This study uses Poisson prospective space-time scan statistics to monitor COVID-19 in Europe.

Adiponectin Suppresses Metastasis of Nasopharyngeal Carcinoma through Blocking the Activation of NF-κB and STAT3 Signaling.

Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial-mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients' survival.

A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.

The lens is a relatively special and simple organ. It has become an ideal model to study the common developmental characteristics among different organic systems. Lens development is a complex process influenced by numerous factors, including signals from the intracellular and extracellular environment. Reactive oxygen species (ROS) are a group of highly reactive and oxygen-containing molecules that can cause endoplasmic reticulum stress in lens cells. As an adaptive response to ER stress, lens cells initiate the unfolded protein response (UPR) to maintain normal protein synthesis by selectively increasing/decreasing protein synthesis and increasing the degradation of misfolded proteins. Generally, the UPR signaling pathways have been well characterized in the context of many pathological conditions. However, recent studies have also confirmed that all three UPR signaling pathways participate in a variety of developmental processes, including those of the lens. In this review, we first briefly summarize the three stages of lens development and present the basic profiles of ROS and the UPR. We then discuss the interconnections between lens development and these two mechanisms. Additionally, the potential adoption of human pluripotent stem-cell-based lentoids in lens development research is proposed to provide a novel perspective on future developmental studies.

Exosomal miRNA Expression Profiling and the Roles of Exosomal miR-4741, miR-32, miR-3149, and miR-6727 on Gastric Cancer Progression.

Objective: Accumulated evidence highlights the biological implications of exosomes in gastric cancer. Herein, we conducted the exosomal miRNA expression profiling and identified potential diagnostic markers for gastric cancer. Methods: Plasma exosomes were isolated and identified from three gastric cancer patients and three healthy participants. Microarrays of exosomal miRNAs were then analyzed. Differentially expressed exosomal miRNAs were screened with fold - change|≥2.0 and p ≤ 0.05. Among them, miR-4741, miR-32, miR-3149, and miR-6727 expressions were verified in tissues and plasma of patients and healthy subjects. ROC curves were conducted for evaluating the diagnostic performance. The roles of miR-32, miR-3149, miR-6727, and miR-4741 on gastric cancer progression were observed by cellular experiments. Results: Isolated exosomes were well characterized by Western blot and transmission electron microscopy as well as nanoparticle-tracking analyses. According to the microarrays, 142 exosomal miRNAs were upregulated, and 34 were downregulated in gastric cancer than healthy subjects. miR-4741 upregulation and miR-32, miR-3149, and miR-6727 downregulations were found in tissues and plasma of gastric cancer patients. The AUCs of miR-4741, miR-32, miR-3149, and miR-6727 were separately 0.8554, 0.9456, 0.7683, and 0.8923. Upregulated miR-32, miR-3149, and miR-6727 as well as downregulated miR-4741 lowered proliferative, migratory, and invasive capacities as well as elevated apoptotic levels of gastric cancer cells. Conclusion: Our study successfully isolated and verified exosomes from plasma of gastric cancer as well as proposed four exosomal miRNAs that could act as promising diagnostic markers and suppress gastric cancer progression.

Analysis of the trend of volatile compounds by HS-SPME-GC-MS and the main factors affecting the formation of rancid odor during the oxidation process of infant nutrition package.

In this study, headspace solid-phase micro-extraction (HS-SPME) coupled with GC-MS was used to analyze the trend of volatile compounds in fresh and oxidative infant nutrition package. Among the volatile compounds, aldehydes and ketones, alcohols, lipids, cycloalkenes, alkanes, alkenes, aromatic hydrocarbons, oxygenated compound were identified. A total of 65 volatile compounds were detected in the fresh nutrition package, whereas 9 new volatile compounds were detected during the accelerated oxidation process, which was oxidized at 45 °C for 4 weeks. The main components of the rancid flavor formed and the relative content of volatile substances gradually changed during the accelerated oxidation process. The volatile substances hexanal, nonanal, and 2-pentylfuran substantially increased. Linalool, α-terpineol, d-limonene, and 1-methoxy-nonane presented an evidently downward trend. The relative content of the newly formed compound 3-hydroxy-2-methylpyran-4-one during the oxidation process was always large, its relative content initially increased, then decreased, and finally increased again. The formation of rancid flavor of the nutrient package was speculated to have been formed by the interaction of hexanal, nonanal, 2-pentylfuran, and 3-hydroxy-2-methylpyran-4-one.