Recent antitumor therapy does not increase Omicron COVID-19 severity in cancer patients: a two-center retrospective study in China.

Background: The impact of anticancer therapy and related clinical factors on the severity of COVID-19 in cancer patients during the Omicron pandemic has not been established. The recent outbreak in China caused predominantly by the BA.5.2 and BF.7 strains of Omicron provided us with the opportunity to observe objectively the impact of this strain in oncology patients. We initiated this two-center retrospective study in China to determine the impact of anti-cancer treatment, other clinical factors, and cancer characteristics on COVID-19 severity in cancer patients infected with coronavirus during the SARS-CoV-2 Omicron variant pandemic in China. Methods: We retrospectively included 554 cancer patients infected with COVID-19 from two medical centers. Data on their anticancer treatment prior to COVID-19 infection and general clinical characteristics (sex, age, past medical history, etc.) were collected. Univariate statistical analysis was performed to identify the factors associated with the severity of COVID-19. Results: Among 554 cancer patients infected with COVID-19, there were 15 (2.7%) severe/critical cases, 86 (15.5%) cases with medium severity, and 453 (81.8%) cases with mild severity. Univariate analysis revealed that advanced age, male sex, worse ECOG score, unvaccinated status, and previous liver, kidney, and brain diseases were associated with more severe COVID-19. However, recent antitumor therapy, including cytotoxic chemotherapy within two weeks did not have a significant correlation with the severity of COVID-19 caused by the Omicron variant. Conclusion: The severity of COVID-19 caused by the Omicron variant is not exacerbated by recent anticancer therapy in cancer patients. Therefore, anticancer therapy should not be discontinued in such cases, especially those with mild severity.

Detection of L-cysteine in urine samples based on CdS/TiO2-modified extended-gate field-effect transistor photoelectrochemical sensor.

A novel extended-gate field-effect transistor (FET) photoelectrochemical (EGFET PEC) sensor was designed for highly sensitive detection of L-cysteine (L-Cys). TiO2 was initially modified on the ITO electrode by the sol-gel dip-coating method and calcined to produce TiO2/ITO. Then, CdS was synthesized on the TiO2 surface by hydrothermal method to obtain the CdS-TiO2 heterojunction material. CdS/TiO2/ITO was connected to the gate of the FET to obtain an EGFET PEC sensor. Under the irradiation of a xenon lamp simulating visible light, the CdS/TiO2 heterojunction composite absorbs light energy to produce photogenerated electron-hole pairs, which have strong photocatalytic oxidation activity and oxidize L-Cys covalently identified by Cd(II) through CdS covalent. These pairs generate a photovoltage that controls the current between the source and the drain to detect L-Cys. Under the optimized experimental conditions, the optical drain current (ID) of the sensor exhibited a good linear relationship with the logarithm of L-Cys in the range of 5.0 × 10-9-1.0 × 10-6 mol/L, and the detection limit was 1.3 × 10-9 mol/L (S/N = 3), which is lower than the values reported by other detection methods. Results showed that the CdS/TiO2/ITO EGFET PEC sensor revealed high sensitivity and good selectivity. The sensor has been used to determine L-Cys in urine samples.

Light-activated cellulose nanocrystals/fluorinated polyacrylate-based waterborne coating: Facile preparation, mechanical and self-healing behavior.

The development of environmental-friendly self-healing nanocomposites has attracted much attention. In this paper, the light-activated cellulose nanocrystals/ fluorinated polyacrylate-based waterborne coating based on the reversible cycloaddition reaction of the coumarin groups was prepared via Pickering emulsion polymerization. The cellulose nanocrystals (CNCs) modified by the PDMAEMA-b-PGMA-b-P(HFBA-co-VBMC) copolymer were studied via FT-IR and TGA. In addition, the dispersity and interface behavior of CNCs before and after modification were investigated by DLS and interfacial tension measurements. Afterwards, we focused on the influence of modified CNCs, PDMAEMA-g-CNC-g- P(HFBA-co-VBMC) (MCNC) dosage on the Pickering emulsion, emulsion polymerization and properties of latex film. The droplet diameter of Pickering emulsion gradually reduced with the increase of MCNC dosage. The MCNC dosage for the minimum average size and optimum stability of latex particles was 1.0 wt%. Moreover, the latex film comprising 1.0 wt% MCNC presented not only high tensile stress (6.0 MPa), large elongation at break (567.70 %) and superior oil/water repellency but also excellent self-healing properties. The outstanding self-healing capability of latex film was attributed to the reversible light-activated dimerization of coumarin groups. The preparation method for the advanced performance waterborne cellulose nanocrystals/fluorinated polyacrylate will provide valuable guidance for the development of versatile materials.

Asthma triggered by extreme temperatures: From epidemiological evidence to biological plausibility.

BACKGROUND: There is rapidly growing evidence indicating that extreme temperature is a crucial trigger and potential activator of asthma; however, the effects of extreme temperature on asthma are inconsistently reported and the its potential mechanisms remain undefined. OBJECTIVES: This review aims to estimate the impacts of extreme heat, extreme cold, and temperature variations on asthma by systematically summarizing the existing studies from epidemiological evidence to biological plausibility. METHODS: We conducted a systematic search in PubMed, Embase, and Web of Science from inception to June 30, 2022, and we retrieved articles of epidemiology and biological studies which assessed associations between extreme temperatures and asthma. This protocol was registered with PROSPERO (CRD42021273613). RESULTS: From 12,435 identified records, 111 eligible studies were included in the qualitative synthesis, and 37 articles were included in the meta-analysis (20 for extreme heat, 16 for extreme cold, and 15 for temperature variations). For epidemiological evidence, we found that the synergistic effects of extreme temperatures, indoor/outdoor environments, and individual vulnerabilities are important triggers for asthma attacks, especially when there is extreme heat or cold. Meta-analysis further confirmed the associations, and the pooled relative risks for asthma attacks in extreme heat and extreme cold were 1.07 (95%CI: 1.03-1.12) and 1.20 (95%CI: 1.12-1.29), respectively. Additionally, this review discussed the potential inflammatory mechanisms behind the associations between extreme temperatures and asthma exacerbation, and highlighted the regulatory role of immunological pathways and transient receptor potential ion channels in asthma triggered by extreme temperatures. CONCLUSIONS: We concluded that both extreme heat and cold could significantly increase the risk of asthma. Additionally, we proposed a potential mechanistic framework, which is important for understanding the disease pathogenesis that uncovers the complex mechanisms of asthma triggered by extreme temperatures and protects the sensitive individuals from impacts of extreme weather events and climate change.

Entropy Information of Pulse Dynamics in Three Stages of Pregnancy.

The aim of the present study is to use entropy to explore the change of pulse generated by normal pregnant women with gestational. Firstly, the subjects were divided into early (E), middle (M), and late (L) three stages according to gestational age. Then, pulse signals of the Chi position of 90 pregnant women at different gestational ages were collected. Secondly, the four entropies, namely fuzzy entropy (FuEn), approximate entropy (ApEn), sample entropy (SamEn), and permutation entropy (PerEn), were applied to the analysis of the long-term pulse changes of the pregnancy. Finally, the related information about pulse in different stages of pregnancy is given by the analysis of four kinds of entropy. Furthermore, the statistical tests are conducted for further comparison, and the descriptive statistics and the results are presented. In addition, boxplots are employed to show the distribution of four entropies of pregnancy. This work has studied the changes in pulse during pregnancy from quantitative and qualitative aspects. Our results show that entropy improves the diagnostic value of pulse analysis during pregnancy and could be applied to facilitate noninvasive diagnosis of pregnant women's physiological signals in the future.

An Intelligent Tongue Diagnosis System via Deep Learning on the Android Platform.

To quickly and accurately identify the pathological features of the tongue, we developed an intelligent tongue diagnosis system that uses deep learning on a mobile terminal. We also propose an efficient and accurate tongue image processing algorithm framework to infer the category of the tongue. First, a software system integrating registration, login, account management, tongue image recognition, and doctor-patient dialogue was developed based on the Android platform. Then, the deep learning models, based on the official benchmark models, were trained by using the tongue image datasets. The tongue diagnosis algorithm framework includes the YOLOv5s6, U-Net, and MobileNetV3 networks, which are employed for tongue recognition, tongue region segmentation, and tongue feature classification (tooth marks, spots, and fissures), respectively. The experimental results demonstrate that the performance of the tongue diagnosis model was satisfying, and the accuracy of the final classification of tooth marks, spots, and fissures was 93.33%, 89.60%, and 97.67%, respectively. The construction of this system has a certain reference value for the objectification and intelligence of tongue diagnosis.

The Research and Development Thinking on the Status of Artificial Intelligence in Traditional Chinese Medicine.

With the rapid development and application of artificial intelligence (AI) in medical field, the diagnostic ways of human health and the social medical structures have changed. Based on the concept of holism and the theory of syndrome differentiation and treatment, TCM realizes comprehensive informatization and intelligence with the help of AI technology in data mining, intelligent diagnosis and treatment, intelligent learning, and decision-making. Furthermore, the intelligent research of TCM technology will further promote the improvement in TCM diagnosis and treatment rules and the leaping development of TCM intelligent instruments. In this article, we performed a systematic review of scientific literature about TCM and AI. Moreover, the practical problems of TCM intellectualization, the current situation and demand of TCM, and the influence of AI in the TCM field are discussed by searching for literature using TCM scientific databases, reference lists, expert consultation, and targeted websites. Finally, we look forward to the application prospects of AI and propose a possible future direction of intelligent TCM in the current health-care system in China.

Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer.

P53 mutation is an important cause of chemoresistance in colorectal cancer (CRC). The investigation and identification of the downstream targets and underlying molecular mechanism of chemoresistance induced by P53 abnormalities are therefore of great clinical significance. In this study, we demonstrated and reported for the first time that leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is a key functional downstream factor and therapeutic target for P53 mutation-induced chemoresistance. Due to its RNA binding function, LRPPRC specifically bound to the mRNA of multidrug resistance 1 (MDR1), increasing MDR1 mRNA stability and protein expression. In normal cells, P53 induced by chemotherapy inhibited the expression of LRPPRC via miR-34a and in turn reduced the expression of MDR1. However, chemotherapy-induced P53/miR-34a/LRPPRC/MDR1 signalling pathway activation was lost when P53 was mutated. Additionally, the accumulated LRPPRC and MDR1 promoted drug resistance. Most importantly, gossypol-acetic acid (GAA) was recently reported by our team as the first specific inhibitor of LRPPRC. In CRC cells with P53 mutation, GAA effectively induced degradation of the LRPPRC protein and reduced chemoresistance. Both in vivo and in vitro experiments revealed that combination chemotherapy with GAA and 5-fluorouracil (5FU) yielded improved treatment outcomes. In this study, we reported a novel mechanism and target related to P53-induced drug resistance and provided corresponding interventional strategies for the precision treatment of CRC.

A systematic and comprehensive analysis of colorectal squamous cell carcinoma: Implication for diagnosis and treatment.

BACKGROUND: This study was aimed at establishing a nomogram for survival prediction of Colorectal squamous cell carcinoma (CSCC), understanding the molecular pathogenesis, exploring a better treatment, and predicting the potential therapeutic agents. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to obtained CSCC patients and the nomogram was performed. Propensity score matching (PSM), Kaplan-Meier analysis, subgroup analysis, and interaction test were used to explore the better treatment strategy for CSCC. Bioinformatics were used to explore the molecular mechanism and potential therapeutic drugs of CSCC. RESULTS: A total of 3949 CSCC patients were studied. The nomogram was constructed and evaluated to have a good performance. We found that the radiotherapy had a better effect than surgery, and the difference between radiotherapy and combined therapy was not significant. 821 differentially expressed genes in CSCC were obtained from GSE6988 dataset. DNA damage repair, mismatch repair, and cell cycle pathways might contribute to CSCC occurrence as indicated by KEGGpathway and GSEA analysis. Transcription factors analysis revealed that TP63 and STAT1 may have an important role in occurrence and development of CSCC. 1607 potential drugs against CSCC were found using the CMAP database, and molecular docking was carried out to show the binding energy between TP63 and drugs. CONCLUSIONS: A good prognosis nomogram was constructed for CSCC. We also have a better understanding of the underlying molecular mechanisms of occurrence and development of CSCC and predicted potential therapeutic drugs, providing a theoretical basis for the treatment of CSCC.

Enduring effect of abuse: Childhood maltreatment links to altered theory of mind network among adults.

Childhood maltreatment (CM) confers a great risk of maladaptive development outcomes later in life, however, the neurobiological mechanism underlying this vulnerability is still unclear. The present study aimed to investigate the long-term consequences of CM on neural connectivity while controlling for psychiatric conditions, medication, and, substance abuse. A sample including adults with (n = 40) and without CM (n = 50) completed Childhood Trauma Questionnaire (CTQ), personality questionnaires, and resting-state functional magnetic resonance imaging scan were recruited for the current study. The whole-brain functional connectivity (FC) was evaluated using an unbiased, data-driven, multivariate pattern analysis method. Relative to controls, adults with CM suffered a higher level of temperament and impulsivity and showed decreased FC between the insula and superior temporal gyrus (STG) and between inferior parietal lobule (IPL) and middle frontal gyrus, STG, and dorsal anterior cingulate cortex (dACC), while increased FC between IPL and cuneus and superior frontal gyrus (SFG) regions. The FCs of IPL with dACC and SFG were correlated with the anxious and cyclothymic temperament and attentional impulsivity. Moreover, these FCs partially mediated the relationship between CM and attentional impulsivity. Our results suggest that CM has a significant effect on the modulation of FC within theory of mind (ToM) network even decades later in adulthood, and inform a new framework to account for how CM results in the development of impulsivity. The novel findings reveal the neurobiological consequences of CM and provide new clues to the prevention and intervention strategy to reduce the risk of the development of psychopathology.

Multi-Gene Phylogeny and Taxonomy of Hydnellum (Bankeraceae, Basidiomycota) from China.

The genus Hydnellum is an important group of stipitate hydnaceous fungi which can form ectomycorrhiza with many species of woody plants. In recent decades, the frequency and number of basidiocarps observed in China have been declining significantly. So far, however, we know little about the species diversity of Hydnellum in China. In this study, we conducted molecular phylogenetic analyses based on sections of multiple loci, including the large subunit of nuclear ribosomal RNA gene (nLSU), the internal transcribed spacer regions (ITS), the small subunit of nuclear ribosomal RNA gene (SSU) and the second-largest subunit of RNA polymerase II gene (RPB2), as well as morphological studies, of collected samples of Hydnellum from China. We also inferred Maximum Likelihood and Bayesian phylogenies for the order Thelephorales from the dataset of the combined nLSU and ITS. This study has revealed the phylogenetic position of Hydnellum in the order Thelephorales, and phylogenetically confirmed ten major clades in Thelephorales; Twenty-nine taxa are proposed, described or reported, including 10 new subgenera (Hydnellum subgenus Hydnellum, subg. Caesispinosum, subg. Croceum, subg. Inflatum, subg. Rhizomorphum, subg. Scabrosum, subg. Spongiosum, subg. Subindufibulatum, subg. Violaceum and subg. Zonatum), 11 new species (Hydnellum atrorubrum, H. atrospinosum, H. bomiense, H. brunneorubrum, H. fibulatum, H. granulosum, H. inflatum, H. rubidofuscum, H. squamulosum, H. sulcatum and H. yunnanense), 3 newly recorded species (H. caeruleum, H. peckii and H. spongiosipes) and 5 notable specimens (Hydnellum sp 1, H. sp 2, H. sp 3, H. sp 4 and H. sp 5). A classification system based on the morphological characteristics (especially the hyphal structure types) and molecular analyses is proposed to accommodate most species in Hydnellum. The distinguishing characters of the subgenera and the new species with their closely related taxa are discussed. A key to the species of Hydnellum from China is provided.

A photoelectrochemical sensor based on an acetylcholinesterase-CdS/ZnO-modified extended-gate field-effect transistor for glyphosate detection.

A new photoelectrochemical enzyme biosensor based on an extended-gate field-effect transistor (EGFET) was constructed for the highly sensitive detection of glyphosate based on the inhibition of acetylcholinesterase (AChE) activity by glyphosate. First, a two-step hydrothermal method was used to introduce ZnO and CdS onto an activated indium tin oxide (ITO) electrode to prepare a CdS/ZnO/ITO electrode. Then, AChE was immobilized on CdS/ZnO/ITO with chitosan to obtain an AChE/CdS/ZnO EGFET sensor. Under optimal experimental conditions, the logarithmic value of glyphosate in the range of 1.0 × 10-15-1.0 × 10-11 mol L-1 exhibited a good linear relationship with the photo-drain current response. The detection limit was 3.8 × 10-16 mol L-1 (signal-to-noise ratio = 3). The results show that the AChE/CdS/ZnO EGFET sensor has extremely high sensitivity and good selectivity. Moreover, the sensor was used for the determination of glyphosate in vegetables, demonstrating its application for the real-time detection of samples.

Demethylzelasteral inhibits proliferation and EMT via repressing Wnt/ß-catenin signaling in esophageal squamous cell carcinoma.

As a kind of tumor commonly seen, no effective treatment is available for esophageal squamous cell carcinoma (ESCC). Therefore, seeking a new treatment is urgent. Demethylzeylasteral (T-96) isolated from Tripterygium wilfordii root bark embraces outstanding good antitumor activity. However, as for the mechanism of T-96 work on ESCC cells, it is rarely reported. In this study, we found that T-96 has inhibition when ESCC cells are proliferating, migrating and cloning. Moreover, relevant effects are influenced by dose and time. And T-96 can result in the stop of G2/M phase and induce apoptosis of ESCC cells. In addition, the expressions of Cyclin B1, Cyclin D1, Bcl-2, PARP1 and Survivin were decreased after starch demethylation. Despite of this, Bax and PARP1's expressions went up. To add up, there was an obvious increase in the expression of E-cadherin, while that of N-cadherin, Vimentin and MMP9 decreased after T-96 treatment. Moreover, the expression of Wnt/ß-Catenin pathway, which concerns proteins ß-Catenin, c-Myc and Wnt3a decreased. Our study shows that T-96 inhibits the proliferation and migration of esophageal cancer cells through Wnt/ß-catenin pathway. Moreover, it gives rise to cell cycle arrest and apoptosis. According to the research results, T-96 tends to be put into use when treating ESCC patients, thus laying the experimental foundation for clinical research.

Multiple-marker phylogeny and morphological evidence reveal two new species in Steccherinaceae (Polyporales, Basidiomycota) from Asia.

Two new wood-inhabiting fungi, Mycorrhaphium subadustum sp. nov. and Trullella conifericola sp. nov., are proposed and described from Asia based on ITS, nrLSU and tef1 molecular phylogeny and morphological characteristics. Mycorrhaphium subadustum is characterized by a stipitate basidiocarp, velutinate pileal surface concentrically zoned, hydnoid hymenophore, a dimitic hyphal system in spine trama and monomitic in context, absence of gloeocystidia, presence of cystidioles and the non-amyloid, cylindrical to ellipsoid basidiospores. Trullella conifericola is characterized by a laterally stipitate basidiocarp with flabelliform to semicircular pileus, hirtellous pileal surface with appressed coarse hair and concentrically zoned and sulcate, tiny pores (10-12 per mm), a dimitic hyphal system, absence of any type of cystidia, short clavate basidia and thin-walled, smooth, cylindrical to allantoid basidiospores. Phylogenetic analyses based on a three-marker dataset were performed using maximum likelihood and Bayesian inference methods. The two new species formed isolated lineages with full support in Steccherinaceae. The distinguishing characters of the two new species as well as allied species are discussed, and a key to species of Mycorrhaphium is provided.

Extracellular vesicles isolated by size-exclusion chromatography present suitability for RNomics analysis in plasma.

BACKGROUND: Extracellular vesicles (EVs), known as cell-derived membranous structures harboring a variety of biomolecules, have been widely used in liquid biopsy. Due to the complex biological composition of plasma, plasma RNA omics analysis (RNomics) is easily affected, thus it is necessary to select an optimal strategy from exiting methods according to the performance for intended application. METHODS: In this study, four different strategies for EVs isolation were performed and compared (i.e. ultracentrifugation (UC), size exclusion chromatography (SEC), and two most frequently-used commercially available isolation kit (ExoQuick and exoEasy). We compared the yield, purity, PCR quantification of RNAs, miRNA-seq analyses and mRNA-seq analyses of RNAs from EVs isolated using four methods. RESULTS: The results showed that the lowest miRNA binding protein AGO2 (Argonaute-2) and the highest EVs-specific miRNA and lncRNA were observed in EVs obtained through SEC, meanwhile the content of the non-specific miRNA was the lowest. Further RNA-Seq data revealed that RNAs obtained via SEC presented more useful reads for both miRNA and mRNA. Furthermore, the mRNA delivered via SEC tended to have a concentration comparable to the ideal FPKM (Fragments Per Kilobase Million) value. CONCLUSIONS: SEC shall be used as an optimal strategy for the isolation of EVs in plasma RNomics analysis.

A phylogenetic overview of the Hydnaceae (Cantharellales, Basidiomycota) with new taxa from China.

The family Hydnaceae (Cantharellales, Basidiomycota) is a group of fungi found worldwide which exhibit stichic nuclear division. The group is highly diverse in morphology, ecology, and phylogeny, and includes some edible species which are popular all over the world. Traditionally, Hydnaceae together with Cantharellaceae, Clavulinaceae and Sistotremataceae are four families in the Cantharellales. The four families were combined and redefined as "Hydnaceae", however, a comprehensive phylogeny based on multiple-marker dataset for the entire Hydnaceae sensu stricto is still lacking and the delimitation is also unclear. We inferred Maximum Likelihood and Bayesian phylogenies for the family Hydnaceae from the data of five DNA regions: the large subunit of nuclear ribosomal RNA gene (nLSU), the internal transcribed spacer regions (ITS), the mitochondrial small subunit rDNA gene (mtSSU), the second largest subunit of RNA polymerase II (RPB2) and the translation elongation factor 1-alpha gene (TEF1). We also produced three more phylogenetic trees for Cantharellus based on 5.8S, nLSU, mtSSU, RPB2 and TEF1, Craterellus and Hydnum both based on the combined nLSU and ITS. This study has reproduced the status of Hydnaceae in the order Cantharellales, and phylogenetically confirmed seventeen genera in Hydnaceae. Twenty nine new taxa or synonyms are described, revealed, proposed, or reported, including eight new subgenera (Cantharellus subgenus Magnus, Craterellus subgenus Cariosi, subg. Craterellus, subg. Imperforati, subg. Lamelles, subg. Longibasidiosi, subg. Ovoidei, and Hydnum subgenus Brevispina); seventeen new species (Ca. laevihymeninus, Ca. magnus, Ca. subminor, Cr. badiogriseus, Cr. croceialbus, Cr. macrosporus, Cr. squamatus, H. brevispinum, H. flabellatum, H. flavidocanum, H. longibasidium, H. pallidocroceum, H. pallidomarginatum, H. sphaericum, H. tangerinum, H. tenuistipitum and H. ventricosum); two synonyms (Ca. anzutake and Ca. tuberculosporus as Ca. yunnanensis), and two newly recorded species (H. albomagnum and H. minum). The distinguishing characters of the new species and subgenera as well as their allied taxa are discussed in the notes which follow them. The delimitation and diversity in morphology, ecology, and phylogeny of Hydnaceae is discussed. Notes of seventeen genera which are phylogenetically accepted in Hydnaceae by this study and a key to the genera in Hydnaceae are provided.

Gambogic acid affects ESCC progression through regulation of PI3K/AKT/mTOR signal pathway.

Esophageal squamous cell carcinoma (ESCC) is an invasive gastrointestinal malignancy and in urgent need of new effective therapies. Gambogic acid (GA) exhibits anti-cancer effects in many cancer cells, but it remains to be determined whether GA has the same effect on ESCC. Here, we reported that GA treatment caused an inhibition in ESCC cell proliferation, migration and invasion. Meanwhile, GA induced dose-dependent apoptosis of ESCC cells, repressed the expression of Bcl2 and up-regulated the levels of Bax protein, cleaved-PARP1 and cleaved-caspase 3/9. Further investigation showed that GA down-regulated the levels of PI3K, p-AKT and p-mTOR, while promoted PTEN expression in ESCC cells. Taken together, we provided the first demonstration that GA exerts anti-tumor effects on ESCC cells presumably through regulating PTEN-PI3K-AKT-mTORpathway, suggestive of a therapeutic potential for ESCC.

Functional Significance and Therapeutic Potential of miRNA-20b-5p in Esophageal Squamous Cell Carcinoma.

Novel therapies tailored to the molecular composition mechanism of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. miR-20b-5p expression was significantly upregulated in cancerous tissues and associated with lymph node metastasis, clinical stage, and overall survival (OS). An analysis of the methylation status of the miR-20b-5p gene indicated that the hypomethylation of the CpG sites located upstream of the miR-20b-5p gene in the ESCC tissues was more frequent than in the adjacent normal tissues, and the methylation status of miR-20b-5p correlated inversely with its expression levels. Notably, a series of gain- and loss-of-function assays elucidated that miR-20b-5p promoted ESCC cell proliferation, migration, and invasion both in vitro and in vivo. Luciferase reporter assays, western blot, and qRT-PCR revealed that RB1 and TP53INP1 were the direct targets of miR-20b-5p. Moreover, the effects of ectopic miR-20b-5p expression were abrogated by RB1 and TP53INP1 overexpression. In contrast, the effects of miR-20b-5p depletion were impaired by RB1 and TP53INP1 knockdown. Treatment with a miR-20b-5p antagomir dramatically increased tumor growth and inhibited RB1 and TP53INP1 protein expression in nude mice. This work provided novel insights on the molecular mechanism of ESCC and further provided suggestions for therapy development.

Hypermethylation of the RSK4 promoter associated with BRAF V600E promotes papillary thyroid carcinoma.

Ribosomal S6 kinase 4 (RSK4) is a putative tumor suppressor gene which is inactivated by epigenetic events in a number human malignancies; however, its role in papillary thyroid carcinoma (PTC) remains largely unknown. The aim of this study was to explore the methylation status of the RSK4 promoter in PTC, and to determine its potential role in thyroid carcinogenesis. Reverse transcription­quantitative PCR (RT­qPCR) and western blot analyses were performed to examine the RSK4 mRNA and protein levels, respectively. Methylation­specific PCR (MSP) and bisulfite genomic sequencing (BGS) were used to analyze methylation status of the RSK4 gene. Sanger sequencing was further carried out to detect the BRAF V600E mutation. Cell proliferation assay was finally performed to evaluate the role of hypermethylation in the growth of PTC cells. The association between RSK4 methylation and the clinicopathological characteristics of patients with PTC was assessed. The methylation frequency of the RSK4 promoter in PTC tissues was higher than that in paired paracancerous tissues. Coincidentally, the RSK4 mRNA levels were also downregulated in PTC tissues when compared with the paracancerous counterparts. The hypermethylation of RSK4 was associated with tumor size and lymph node metastasis. Furthermore, the BRAF V600E mutation may influence RSK4 expression and methylation. Moreover, RSK4 hypermethylation was observed in thyroid cancer cell lines, which was consistent with a lack of RSK4 expression. Upon the 5­Aza­deoxycytidine treatment of thyroid cancer cells, RSK4 expression was significantly upregulated, while cell proliferation was inhibited. On the whole, the findings of the present study demonstrate that the hypermethylation of the RSK4 promoter may be one of the mechanisms responsible for the poor RSK4 expression in PTC. Thus, these data suggest that RSK4 may serve as a molecular target for the early diagnosis and treatment of PTC.

Correction to: Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC).

In the original publication of this manuscript [1], Fig. 6 contains a repeated image in error (the left image of 'Migration' and the left image of 'Invasion').