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Abstract Background Diabetes, a global epidemic, is the leading cause of mortality globally. The aim of this study is to get better understanding of pathophysiology of diabetes. Methods Palmitic acid (PA)-treated β-cells, db/db mice and high fat diet (HFD)-fed mouse model of type 2 diabetes were established. H&E was used to assess the histological changes of pancreas. IHC, FISH, western blot or qRT-PCR was employed to detect the expression of key molecules in primary islets or lipotoxic β-cells. Cell behaviors were detected by MTT, EdU incorporation assay, TUNEL assay and glucose-induced insulin secretion (GSIS). The associations among circMlxipl, Mbnl1 and Rbbp6 were validated by RIP and RNA pull-down assays, and the direct binding between Hdac3 and Mbnl1 promoter was examined by ChIP and luciferase assays. Co-IP was employed to assess the interaction between ChREBP and Rbbp6, as well as the ubiquitination of ChREBP. Results Hdac3 and ChREBP were upregulated, but Mbnl1 and circMlxipl were downregulated in islets from diabetic mice and lipotoxic β-cells. Mbnl1 overexpression protected against PA-induced impairments in lipotoxic β-cells through modulating back-splicing of circMlxipl and suppressing ChREBP. Hdac3 served as a transcriptional repressor of Mbnl1, and it was implicated in circMlxipl-mediated protection via regulating ChREBP expression in lipotoxic β-cells. Lack of circMlxipl inhibited Rbbp6-mediated ubiquitin-proteasomal degradation of ChREBP in lipotoxic β-cells. In vivo studies revealed that Hdac3 knockdown or Mbnl1 overexpression alleviated diabetes symptoms through circMlxipl-regulated ChREBP in diabetic mice. Conclusion Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage.

Objective To explore the combined effect of pre-pregnancy body mass index (BMI) and assisted reproductive technology (ART) on the risk of pregnancy-induced hypertension (PIH).Methods This retrospective cohort study included 3,220,103 women with singleton pregnancies from the National Vital Statistics System database for 2021. The outcome was the occurrence of PIH. Logistic regression analyses were utilized to assess the association between pre-pregnancy BMI and ART and PIH. To evaluate the interaction of pre-pregnancy BMI and ART on PIH, the relative excess risk of interaction (RERI), the attributable proportion due to interaction (API), and synergy index (SI) were applied.Results Of these 3,220,103 women, 302,789 [9.40% (95%CI: 9.37%-9.43%)] occurred PIH. Women with a pre-pregnancy BMI ≥25 kg/m2 [odds ratio (OR)=2.06, 95% confidence interval (CI): 2.04-2.08] or using ART (OR = 1.43, 95%CI: 1.39-1.47) were related to a higher risk of PIH. There was a positive additive interaction of pre-pregnancy BMI and ART on the risk of PIH, with an interaction RERI, API, and SI of 0.20 (95%CI: 0.08-0.33), 0.07 (95%CI: 0.03-0.11), and 1.13 (95%CI: 1.05-1.21), respectively. Stratified analyses demonstrated that the positive additive interactions of pre-pregnancy BMI and ART on PIH were observed in women aged

Tremella fuciformis (TF) stem accounts for about 10% of the whole mushroom, and most of them are dumped without utilization. To effectively utilize the waste, the effects of fine grinding and superfine grinding technology on the processing characteristics and physicochemical properties of Tremella fuciformis stem powder (TFSP) were investigated, and the effects of TFSP on the quality of steamed bun were analyzed. The findings indicate that the specific surface area of superfine Tremella fuciformis stem powder (STFSP) is 1.6 times larger than that of fine Tremella fuciformis stem powder (FTFSP). Despite this, the infrared spectra of STFSP and FTFSP are similar. The water solubility index and oil holding capacities of STFSP saw an increase of 18.81%, whereas its water holding capacity decreased by 11.34%. Superfine grinding not only enhanced the processing characteristics but also stabilized the powder form. Moreover, steamed buns incorporating 4% STFSP were judged to have the optimal taste. Superfine grinding significantly influences the physicochemical properties of TFSP, resulting in enhanced quality of steamed buns.

The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment. Phagocytosis is one of the most effective defense strategies against microbial challenge mainly performed by classical ‘professional’ phagocytes (including monocytes, macrophages and granulocytes). They contain, kill and process the internalized pathogens for antigen presentation by providing antigenic ligands to initiate activation and clonal expansion of T and B cells, which bridge the innate and adaptive immunity. The discovery of phagocytic B cells in teleost fish has broken the paradigm that primary vertebrate B cells are lack of phagocytosis of particulates, as well as led to the investigation of phagocytic activity of mammalian B-1 B cells. The active phagocytic, microbicidal capabilities and antigen presentation in teleost phagocytic B cell have demonstrated to be similar as professional phagocytes, providing a potential impact on development of new vaccination strategies to prevent and control infectious diseases. In this review, we aim to address current progress on the antimicrobial role of phagocytic B cells in teleost fish by comparing it with other professional phagocytes and mammalian B-1 B cells, and provide the application prospect of phagocytic B cells in developing vaccines as well as the prevention of fish diseases.

The widespread vibration is one of the most promising energy sources for IoT and small sensors, and broad-frequency vibration energy harvesting is important. Triboelectric nanogenerators (TENGs) can convert vibration energy into electrical energy through triboelectricity and electrostatic induction, providing an effective solution to the collection of broad-frequency vibration energy. Also, the power supply in constrained and compact spaces has been a long-standing challenge. Here, a miniaturized power supply (MPS) based on a broad-frequency vibration-driven triboelectric nanogenerator (TENG) is developed. The size of the MPS is 38 mm × 26 mm × 20 mm, which can adapt to most space-limited environments. The TENG device is optimized through theoretical mechanical modeling for the external stimuli, it can efficiently harvest vibrational energy in the frequency range of 1–100 Hz and has a high output power density of 134.11 W/cm3. The developed device demonstrates its practical application potential in powering small electronics like LEDs, watches, and timers.

AbstractPurpose Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire.Methods This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively.Results This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models.Conclusion Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Abstract Background This cross‐sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. Methods 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. Results Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: “High weed pollen and house dust mites (HDMs) sensitization” (8.87%), Class 2: “HDMs dominated sensitization” (38.38%), Class 3: “High HDMs and animal dander sensitization” (6.95%), Class 4: “Low/no aeroallergen sensitization” (45.80%). Western cohort: Class 1: “High weed pollen sensitization” (26.14%), Class 2: “High multi‐pollen sensitization” (15.02%), Class 3: “HDMs‐dominated sensitization” (10.33%), Class 4: “Low/no aeroallergen sensitization” (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. Conclusions Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

BackgroundStroke is the second leading cause of death and the third leading cause of disability worldwide, with ischemic stroke (IS) being the most prevalent. A substantial number of irreversible brain cell death occur in the short term, leading to impairment or death in IS. Limiting the loss of brain cells is the primary therapy target and a significant clinical issue for IS therapy. Our study aims to establish the gender specificity pattern from immune cell infiltration and four kinds of cell-death perspectives to improve IS diagnosis and therapy.MethodsCombining and standardizing two IS datasets (GSE16561 and GSE22255) from the GEO database, we used the CIBERSORT algorithm to investigate and compare the immune cell infiltration in different groups and genders. Then, ferroptosis-related differently expressed genes (FRDEGs), pyroptosis-related DEGs (PRDEGs), anoikis-related DEGs (ARDEGs), and cuproptosis-related DEGs (CRDEGs) between the IS patient group and the healthy control group were identified in men and women, respectively. Machine learning (ML) was finally used to generate the disease prediction model for cell death-related DEGs (CDRDEGs) and to screen biomarkers related to cell death involved in IS.ResultsSignificant changes were observed in 4 types of immune cells in male IS patients and 10 types in female IS patients compared with healthy controls. In total, 10 FRDEGs, 11 PRDEGs, 3 ARDEGs, and 1 CRDEG were present in male IS patients, while 6 FRDEGs, 16 PRDEGs, 4 ARDEGs, and 1 CRDEG existed in female IS patients. ML techniques indicated that the best diagnostic model for both male and female patients was the support vector machine (SVM) for CDRDEG genes. SVM’s feature importance analysis demonstrated that SLC2A3, MMP9, C5AR1, ACSL1, and NLRP3 were the top five feature-important CDRDEGs in male IS patients. Meanwhile, the PDK4, SCL40A1, FAR1, CD163, and CD96 displayed their overwhelming influence on female IS patients.ConclusionThese findings contribute to a better knowledge of immune cell infiltration and their corresponding molecular mechanisms of cell death and offer distinct clinically relevant biological targets for IS patients of different genders.

Background: No comprehensive multicenter study of sensitization patterns among patients with allergic rhinitis (AR) to various common pollen allergens was available nationwide, and risks factors of pollen-induced allergic rhinitis (PiAR) in mainland China was unclear. This study aimed to fill this gap. Methods: A multicenter study was performed on 736 AR patients aged below 18 from four regions of mainland China. Patients completed a standardized questionnaire asking for the environmental risk factors and AR severity, and undertook skin prick tests (SPT) with 14 common pollen allergens. Findings: Among the 736 patients, 341 patients (46.33%) suffered at least one positive pollen allergen sensitization. The positive rate of pollen allergens was significantly higher in the high-age group (Damato et al., 2007; Wang et al., 2018; Luo et al., 2016; Demoly et al., 2011; Sampson and Albergo, 1984; Li et al., 2009; Luo et al., 2021; Ziska and Beggs, 2011; Melén et al., 2020; Jensen-Jarolim, 2017; Rönmark et al., 2017; Ge et al., 2017) [6-17] than the low-age group ( ≤ 5), while no significant difference was found between the sexes. The sensitizations to pollen allergens varied widely among four geographical areas. The positive rate was higher in north China and west China than in east China, and south China had the lowest positive rate. The region of residence, ages, ethnic minorities, history of pollen exposure, the material of living room floor and material of pillow were statistically significant risks of PiAR. Interpretation: This study provides new insights into the pollen allergens sensitization characteristics in AR and the factors affecting PiAR in mainland China.

Abstract Purpose This study aimed to explore the role of long non-coding RNA (lncRNA) BDNF-AS in the progression of multiple myeloma (MM). Methods The expression of BDNF-AS, miR-125a-5p, and miR-125b-5p in MM serum and cell lines were detected by quantitative reverse transcriptase PCR (qRT-PCR). The binding relationships between miR-125a/b-5p and BDNF-AS or Bcl-2 were predicted by Starbase and verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining assay. Cell migration was evaluated by wound healing assay. The expression levels of apoptosis-related proteins were evaluated by Western blot analysis. The role of BDNF-AS was also investigated in a xenograft tumor model in vivo. Results BDNF-AS was significantly upregulated, while miR-125a-5p and miR-125b-5p were downregulated in MM serum and corresponding cancer cell lines. Knockdown of BDNF-AS effectively inhibited the proliferation and migration of MM.1S and U266 cells, and co-transfection of miR-125a-5p or miR-125b-5p inhibitor and sh-BDNF-AS enhanced cell proliferation and migration compared with that in sh-BDNF-AS group. Knockdown of miR-125a-5p or miR-125b-5p significantly enhanced the proliferation and migration of MM.1S and U266 cells, and co-transfection of sh-Bcl-2 and miR-125a/b-5p inhibitor inhibited cell proliferation compared with that in miR-125a/b-5p inhibitor group. Moreover, knockdown of BDNF-AS increased the expression levels of apoptosis-related proteins (cleaved caspase 3 and cleaved PARP), while knockdown of miR-125a-5p or miR-125b-5p reduced the expression levels of these apoptosis-related proteins compared with knockdown of BDNF-AS. Furthermore, knockdown of BDNF-AS effectively suppressed MM tumor growth in vivo. Conclusion Our findings revealed that knockdown of BDNF-AS inhibited the progression of MM by targeting the miR-125a/b-5p-Bcl-2 axis, indicating that BDNF-AS might serve as a novel drug target for MM.

Abstract Background Listeria monocytogenes is one of the deadliest foodborne pathogens. The bacterium can tolerate severe environments through biofilm formation and antimicrobial resistance. This study aimed to investigate the antimicrobial susceptibility, resistance genes, virulence, and molecular epidemiology about Listeria from meat processing environments. Methods This study evaluated the antibiotic resistance and virulence of Listeria isolates from slaughtering and processing plants. All isolates were subjected to antimicrobial susceptibility testing using a standard microbroth dilution method. The harboring of resistant genes was identified by polymerase chain reaction. The multilocus sequence typing was used to determine the subtyping of the isolates and characterize possible routes of contamination from meat processing environments. The virulence of different STs of L. monocytogenes isolates was evaluated using a Caco-2 cell invasion assay. Results A total of 59 Listeria isolates were identified from 320 samples, including 37 L. monocytogenes isolates (62.71%). This study evaluated the virulence of L. monocytogenes and the antibiotic resistance of Listeria isolates from slaughtering and processing plants. The susceptibility of these 59 isolates against 8 antibiotics was analyzed, and the resistance levels to ceftazidime, ciprofloxacin, and lincomycin were as high as 98.31% (L. m 37; L. innocua 7; L. welshimeri 14), 96.61% (L. m 36; L. innocua 7; L. welshimeri 14), and 93.22% (L. m 35; L. innocua 7; L. welshimeri 13), respectively. More than 90% of the isolates were resistant to three to six antibiotics, indicating that Listeria isolated from meat processing environments had high antimicrobial resistance. Up to 60% of the isolates harbored the tetracycline-resistance genes tetA and tetM. The frequency of ermA, ermB, ermC, and aac(6′)-Ib was 16.95, 13.56, 15.25, and 6.78%, respectively. Notably, the resistant phenotype and genotype did not match exactly, suggesting that the mechanisms of antibiotic resistance of these isolates were likely related to the processing environment. Multilocus sequence typing (MLST) revealed that 59 Listeria isolates were grouped into 10 sequence types (STs). The dominant L. monocytogenes STs were ST5, ST9, and ST121 in the slaughtering and processing plant of Jiangsu province. Moreover, ST5 subtypes exhibited high invasion in Caco-2 cells compared with ST9 and ST121 cells. Conclusion The dominant L. monocytogenes ST5 persisted in the slaughtering and processing plant and had high antimicrobial resistance and invasion characteristics, illustrating a potential risk in food safety and human health.

Plasma cells are terminally differentiated antibody-secreting B lymphocytes that contribute to humoral immunity by producing large numbers of antibodies. Increasing evidence suggests that teleost fish B cells share certain characteristics with mammalian B1 B cells, including antibody-secreting, phagocytic, and antigen-presenting capacities. However, the difference between mature B cells and plasma cells remains unclear. In this study, we found that, based on their light-scattering characteristics, tilapia anterior kidney (AK) leukocytes can be categorized into two IgM+ B-cell subsets: the lymphoid (L) gate and granulocyte–monocyte/macrophage (G-M) subsets. G-M gate cells are more numerous than L-gate cells and have higher mean fluorescence, but lower forward scatter and side scatter. We analyzed the morphological and ultrastructural features of sorted IgM+ cells and found that L-gate IgM+ cells have a high nucleus–cytoplasm ratio and lymphocyte-like morphology, whereas G-M gate IgM+ cells have a small nucleus, more abundant endoplasmic reticulum, and a larger number of mitochondria, and have a plasma cell-like or macrophage-like morphology. To further characterize the cell types, we examined the specific patterns of expression of B-cell- and T-cell-related genes. We found that B-cell-specific genes were expressed by both L-gate and G-M gate IgM+ cells, and that G-M gate IgM+ cells secreted extremely high levels of IgM. However, T-cell-related genes were highly expressed only in L-gate IgM– cells. These results suggest that G-M gate IgM+ cells are similar to plasma-like cells, with high antibody-secreting capacity. Given that G-M gate cells include the granulocyte, monocyte, and macrophage cell types, but not B cells, monocyte/macrophage markers were used to investigate the cell types further. A macrophage receptor with a collagenous structure was frequently observed, and macrophage-expressed gene-1 was highly expressed, in the G-M gate IgM+ cells. Phagocytic capacity, as determined by ingestion of beads or bacteria, was significantly higher in G-M gate IgM+ cells than in L-gate IgM+ cells, as was antigen-processing capacity. Our findings show that tilapia AK leukocytes can be divided into two IgM+ B-cell subsets and that G-M gate IgM+ cells resemble plasma-like cells, having high antibody-secreting, phagocytic, and antigen-presenting capacities. Thus, this study increases our understanding of the functions of teleost fish plasma-like cells.

Abstract Aims/Introduction Type 2 diabetes mellitus is correlated with systemic atherosclerosis. Statin therapies have been proved to reduce low‐density lipoprotein cholesterol (LDL‐C) level, protecting type 2 diabetes mellitus patients from cardiovascular events. Recently, more interest has been focused on the regression of lower extremity atherosclerotic disease (LEAD) for the potential prevention of amputation. However, the effects of pitavastatin and atorvastatin on LEAD in type 2 diabetes mellitus patients have not been directly compared. Materials and Methods This study compared the effects of pitavastatin and atorvastatin on femoral total plaque areas (FTPA), and lipids and glucose metabolism in type 2 diabetes mellitus patients with elevated LDL‐C level and LEAD. Type 2 diabetes mellitus patients with LDL‐C level >2.6 mmol/L and LEAD were randomly assigned to receive either pitavastatin 2 mg/day or atorvastatin 10 mg/day for 48 weeks. FTPA were measured at baseline and the end of the study. Levels of glucose and lipids profile were measured periodically. The efficacy was evaluated in 63 patients. Results The percentage change in FTPA measurements was similar between the pitavastatin group and atorvastatin group (−17.79 ± 21.27% vs −14.34 ± 16.33%), as were the changes in LDL‐C (−44.0 ± 18.0% vs −40.3 ± 18.2%) and triglyceride (17.6 ± 20.0% vs 16.2 ± 17.0%). However, the level of high‐density lipoprotein cholesterol was significantly higher in the pitavastatin group compared with the atorvastatin group after 48 weeks of treatment (12.9 ± 10.3% vs 7.2 ± 11.7%, P

The grain size effect is one of the fundamental characteristics of semiconductor gas sensors. However, it has not been fully understood due to the absence of studies on the volume-depleted grains. In this work, the gas-sensitive SnO2 quantum dots (QDs) from partial depletion to volume depletion are prepared to discuss the size effects. A facile aqueous-based method is used to prepare the size-controllable SnO2 QDs of 2.0–12.6 nm. The resistance shows a monotonically negative size effect while the response reaches the optimization when the grain radius is comparable to the depletion layer width. It is suggested that the design of highly sensitive gas sensors should consider the equal importance of the control of grain size and depletion layer width. The computational results illustrate size-dependent energy level of donors and number of quasi-free electrons, which are responsible for the negative size effect of resistivity in the volume-depleted SnO2 crystallites. This work provides a comprehensive understanding of grain size effects from partial depletion to volume depletion in semiconductor gas sensors.

Size-controllable tin oxide (SnO2) quantum dots (QDs) in aqueous solution were prepared by using stannous chloride and thiourea as source materials and the hydrothermal treatment was employed for size control during the self-assembly of SnO2 QDs. The size effects on structural and optical properties of QDs were discussed. The prepared QDs were confirmed to be of rutile structure with (2 0 2), (2 1 1) and (3 3 0) facets observed. The crystal lattice constants changed their dimensions during grain growth and secondary grain boundaries appeared if grain size was over 7 nm. The composition and valence states were found independent with grain size. A negative correlation was observed between size and band gap, which exhibited much greater values than the calculation results from the theory of effective mass approximation and illustrated a strong quantum confinement in the present SnO2 QDs. The size effect of photoluminescence property illustrated a fluorescence inhibition, which could be ascribed to the additional energy levels provided by the lattice distortions at secondary grain boundaries. The depletion region in QDs was extended by these defects, which strengthened the quantum confinement effect.

Summary: Background: Because of the significant regional differences in the distribution of allergens, the relationship between anaphylaxis and allergic sensitization is complex in China. Using this large-scale epidemiologic survey, we explore the potential patterns of sensitization to common allergens in mainland China and investigate their relationship with various clinical symptoms. Method: The participants were recruited from 13 medical centers in mainland China from October 2019 to June 2021. Skin prick test (SPT) results that cover 18 common allergens were utilized to diagnose atopic sensitization. The demographic characteristics and clinical information were collected through questionnaires during routine medical follow-up. Latent class analysis (LCA) was conducted to determine the optimal sensitization patterns. The logistic regression was used to assess the associations of different sensitization patterns with allergy symptoms. Findings: A total of 1089 patients who had a positive SPT to at least one of 18 allergens were included for formal analysis. An optimal LCA model with 4 classes was obtained in this study, and the corresponding labels were as follows: Class1, house dust mite sensitization; Class2, low pollen sensitization; Class3, middle pollen sensitization; Class4, high pollen sensitization. The prevalence of different classes varied widely in geographical distribution, which was characterized by Class1 being very common in south and east as well as Class2 in north and west of China. Compared with patients in Class1, those in middle and high pollen sensitization clusters had the higher odds ratios (ORs) of allergic rhinitis and allergic conjunctivitis when controlling for other confounders. However, there was no significant difference between low pollen sensitization and house dust mite sensitization groups in the risks for various clinical performances except dermatitis. Additionally, the adjusted ORs (95% confidence interval) of allergic conjunctivitis and dermatitis for participants in pollen sensitization clusters (Class2, 3 and 4) were 1.56 (1.18, 2.06) and 1.43 (1.09, 1.88) respectively compared with those in Class1. Interpretation: In this study, we identified four sensitization clusters with specific risks of various clinical symptoms using common allergens by adopting LCA. Our findings may contribute to improved diagnosis and potential immunotherapy approaches to allergy in mainland China. Funding: This study was supported by the National Natural Science Foundation of China (81802076 and 81871736), the Guangzhou Science and Technology Foundation (202102010327), the Foundation of SKLRD (MS-2019-06 and Z-2022-09), and the Foundation of GYYY (ZH201904) and ZNSA-2020012.

Mugwort is a common pollen allergen in western China, and this study aimed to investigate the patterns of molecular sensitization to major grass pollen allergens (mugwort, ragweed, bermuda grass, and timothy grass) and cross-reactive carbohydrate determinants (CCD) in children who were sensitized to mugwort in western China. Serum-specific IgE (sIgE) of major allergen components and CCD were detected among 121 mugwort SPT-positive children via the EUROBlotMaster system if the mugwort-sIgE was positive (MSP). A CCD inhibition test was further performed on the serum of patients with positive CCD-sIgE. Latent class analysis was used to identify the patterns of potential sensitization to major grass pollen allergens. Of a total of 100 patients with mugwort-sIgE positive (MSP), 52.0, 41.0, and 31.0% of them were positive to Art v 1, Art v 3, and Art v 4, respectively. An optimal model with three latent classes was determined using grass pollen allergens, components, and CCD. The sensitization patterns can be summarized as (1) MSP and cosensitized to ragweed, bermuda grass, and timothy grass (23.74%); (2) MSP and cosensitized to Art v 1 (54.08%); (3) MSP and cosensitized to Art v 4, Cyn d 12, Phl p 12 (22.18%). Additionally, CCD sIgE levels had a significant positive correlation with ragweed, bermuda grass, and timothy grass (P < 0.05), and CCD-Inhibitor can highly inhibit the above allergens sIgE. Our findings suggest that Art v 4 was the typical cross-reaction component of mugwort, which is cosensitized to Phl p 12 and Cyn d 12. A wide cross-reaction among ragweed, bermuda grass, and timothy grass caused by CCD was observed.

Atomically thin two-dimensional (2D) CN sheets have attracted extensive attention in the field of photocatalysis because of their shorter diffusion path of photogenerated carriers and abundant surface reaction sites than bulk CN. However, 2D CNs still exhibit poor visible-light photocatalytic activity because of a strong quantum size effect. Here, PCN-222/CNs vdWHs were successfully constructed using the electrostatic self-assembly method. The results showed that PCN-222/CNs vdWHs with 1 wt.% PCN-222 enhanced the absorption range of CNs from 420 to 438 nm, which improved the absorption capacity of visible light. Additionally, the hydrogen production rate of 1 wt.% PCN-222/CNs is four times that of the pristine 2D CNs. This study provides a simple and effective strategy for 2D CN-based photocatalysts to promote visible light absorption.

The sympathoadrenal system has been shown to stimulate the secretory activity of enteroendocrine cells, although the response is transient. Our aim was to investigate the effects of long-term catecholamine excess on circulating glucagon-likepeptide-1 (GLP-1) levels in patients with pheochromocytoma/paraganglioma (PPGL). Thirty patients diagnosed with PPGL were analyzed. A significant negative association was observed between fasting plasma GLP-1 levels and elevated plasma-free metanephrine (r=−0.407,p=0.026). After adjustment for age, sex, body mass index (BMI), serum creatinine, and the presence of hyperglycemia, the negative association between plasma GLP-1 and metanephrine persisted by multiple linear regression analysis (β=−0.493,p=0.013). Positive correlations between fasting glucose and plasma metanephrine (r=0.380,p=0.038) and normetanephrine levels (r=0.450,p=0.013) were also found. Mean fasting levels of total GLP-1 increased significantly from 25.81 to 39.01 pmol/L (p=0.017) after PPGL resection. In conclusion, long-term overproduction of catecholamines appears to induce suppression of GLP-1 production compared to an acute response to a stress stimulus. Further studies are required to elucidate the mechanism of GLP-1 secretion with chronic exposure to catecholamine.

Background. Even though nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling has been associated with the pathogenesis of multiple heart conditions, data on roles of Nrf2 within atrial fibrillation (AF) still remain scant. The present investigation had the aim of analyzing Nrf2-overexpressing role/s upon bone mesenchymal stem cell- (BMSC-) derived exosomes in rats with AF. Methods. Exosomes were collected from control or Nrf2 lentivirus-transduced BMSCs and then injected into rats with AF through the tail vein. AF duration was observed using electrocardiography. Immunohistochemical staining was then employed for assessing Nrf2, HO-1, α-SMA, collagen I, or TGF-β1 expression profiles within atrial myocardium tissues. Conversely, Masson staining was utilized to evaluate atrial fibrosis whereas apoptosis within myocardia was evaluated through TUNEL assays. In addition, TNF-α, IL-1β, IL-4, or IL-10 serum expression was assessed through ELISA. Results. Results of the current study showed significant downregulation of Nrf2/HO-1 within AF rat myocardia. It was found that injection of the control or Lv-Nrf2 exosomes significantly alleviated and lowered AF timespans together with reducing cardiomyocyte apoptosis. Moreover, injection of Lv-Nrf2 exosomes essentially lowered AF-driven atrial fibrosis and also inhibited inflammatory responses in the rats with AF. Conclusion. Delivery of BMSC-derived exosomes using overexpressed Nrf2 inhibited AF-induced arrhythmias, myocardial fibrosis, apoptosis, and inflammation via Nrf2/HO-1 pathway triggering.

Background. Essential hypertension (EH) is a common and multifactorial disorder that is likely to be influenced by multiple genes. The methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 and rs1801131 polymorphisms influence MTHFR enzyme activity and plasma homocysteine concentration. In addition, variations in MTHFR functions likely play roles in the etiology of EH. Thus far, a large number of studies investigating the associations between the MTHFR polymorphisms and EH have provided controversial or inconclusive results. To better assess the purported relationship, we performed a comprehensive analysis of 52 published studies. Objective and Methods. Eligible studies were identified by searching the PubMed, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the potential association between the MTHFR rs1801133 polymorphism and EH. Results. Overall, 10712 patients and 11916 controls were involved; we observed significantly increased association between the MTHFR rs1801133 polymorphism and EH risk (such as T vs. C: OR=1.38, 95% CI=1.25−1.54, P≤0.001), with similar results evident within race subgroups (such as Asian: T vs. C: OR=1.47, 95% CI=1.30−1.67, P≤0.001; compared to Chinese: T vs. C: OR=1.54, 95% CI=1.33−1.79, P≤0.001). Similar associations were also found in subgroups defined by the source of controls and genotype methods. To our regret, based on the limited studies, no association was detected for rs1801131 polymorphism. Conclusions. Our study provides evidence that the MTHFR rs1801133 null genotype may increase EH risk. Future studies with larger sample sizes are warranted to evaluate this association in more detail.

Teleost fish anterior kidney (AK) is an important hematopoietic organ with multifarious immune cells, which have immune functions comparable to mammalian bone marrow. Myeloid and lymphoid cells locate in the AK, but the lack of useful specific gene markers and antibody-based reagents for the cell subsets makes the identification of the different cell types difficult. Single-cell transcriptome sequencing enables single-cell capture and individual library construction, making the study on the immune cell heterogeneity of teleost fish AK possible. In this study, we examined the transcriptional patterns of 11,388 AK leukocytes using 10× Genomics single-cell RNA sequencing (scRNA-seq). A total of 22 clusters corresponding to five distinct immune cell subsets were identified, which included B cells, T cells, granulocytes, macrophages, and dendritic cells (DCs). However, the subsets of myeloid cells (granulocytes, macrophages, and DCs) were not identified in more detail according to the known specific markers, even though significant differences existed among the clusters. Thereafter, we highlighted the B-cell subsets and identified them as pro/pre B cells, immature/mature B cells, activated B/plasmablasts, or plasma cells based on the different expressions of the transcription factors (TFs) and cytokines. Clustering of the differentially modulated genes by pseudo-temporal trajectory analysis of the B-cell subsets showed the distinct kinetics of the responses of TFs to cell conversion. Moreover, we classified the T cells and discovered that CD3+CD4−CD8−, CD3+CD4+CD8+, CD4+CD8−, and CD4−CD8+ T cells existed in AK, but neither CD4+CD8− nor CD4−CD8+ T cells can be further classified into subsets based on the known TFs and cytokines. Pseudotemporal analysis demonstrated that CD4+CD8− and CD4−CD8+ T cells belonged to different states with various TFs that might control their differentiation. The data obtained above provide a valuable and detailed resource for uncovering the leukocyte subsets in Nile tilapia AK, as well as more potential markers for identifying the myeloid and lymphoid cell types.

The class B scavenger receptors (scarb) are members of important pattern recognition receptors which play key roles for host immune response to pathogen infection. In the present study, two scarb member 2 paralogous (Onscarb2a and Onscarb2c) were identified and characterized in Nile tilapia. Onscarb2a was identified with an open reading frame (ORF) of 1593 bp which encoded a polypeptide of 530 amino acids, and Onscarb2c was consisting of an ORF of 1446 bp which encoded a polypeptide of 461 amino acids. Both Onscarb2a and Onscarb2c share high sequence identity/similarity with their counterparts from other teleost species. Multiple sequence alignment and phylogenetic tree analyses show that scarb2c from teleost fish is more closely related to other vertebrate scarb2s. Gene expression studies revealed that both scarb2a and scarb2c were highly expressed in liver, with the lowest expression in muscle in healthy tilapia. After challenges with Streptococcus agalactiae and Aeromonas hydrophila, both Onscarb2a and Onscarb2c were markedly up-regulated in liver and head kidney. In addition, the up-regulation of Onscarb2a and Onscarb2c were also detected in head kidney monocytes/macrophages and hepatocytes. In conclusion, this study revealed that Onscarb2a and Onscarb2c might play important roles in the innate immune responses to bacterial invasion in Nile tilapia.

Clostridium perfringens is a gram-positive, anaerobic, spore-forming bacterium capable of producing four major toxins which cause disease symptoms and pathogenesis in humans and animals. C. perfringens strains carrying enterotoxins can cause food poisoning in humans and are associated with meat consumption. An endolysin, named LysCP28, is encoded by orf28 from C. perfringens bacteriophage BG3P. This protein has an N-terminal glycosyl–hydrolase domain (lysozyme) and a C-terminal SH3 domain. Purified LysCP28 (38.8 kDa) exhibited a broad spectrum of lytic activity against C. perfringens strains (77 of 96 or 80.21%), including A, B, C, and D types, isolated from different sources. Moreover, LysCP28 (10 μg/mL) showed high antimicrobial activity and was able to lyse 2 × 107 CFU/mL C. perfringens ATCC 13124 and C. perfringens J21 (animal origin) within 2 h. Necessary due to this pathogenic bacterium’s ability to form biofilms, LysCP28 (18.7 μg/mL) was successfully evaluated as an antibiofilm agent in both biofilm removal and formation inhibition. Finally, to confirm the efficacy of LysCP28 in a food matrix, duck meat was contaminated with C. perfringens and treated with endolysin (100 µg/mL and 50 µg/mL), which reduced viable bacteria by 3.2 and 3.08 units-log, respectively, in 48 h at 4 °C. Overall, the endolysin LysCP28 could potentially be used as a biopreservative to reduce C. perfringens contamination during food processing.

The oxygen vacancies (VO) play an essential role in the gas-sensing mechanism of semiconductor devices. A diffusion equation is established to describe the VO behaviors during a cooling process based on the model of gradient-distributed oxygen vacancies. Numerical solutions of the diffusion equation are found to illustrate the VO distribution in grains. The gradient of VO distribution is of negative dependence on the cooling rate, which also influences the average VO density in the depletion layer. The migration of oxygen vacancies in cooling process could be interrupted by quenching and it is restarted by the re-annealing process. The VO distributing process is illustrated by three stages from initial uniform distribution to final gradient profile via a transient stage. The influence of VO distribution on gas-sensing characteristics of semiconductor grains is discussed. Potential opportunities are found to control the gas sensor characteristics by a designed annealing process.

Non-coding RNAs (ncRNAs) have gained increasing attention as their diverse roles in virulence and environmental stress in Listeria monocytogenes have become clearer. The ncRNA rliB is an atypical member of the CRISPR family, conserved at the same genomic locus in all analyzed L. monocytogenes genomes and also in other Listeria species. In this study, rliB defective mutants (Lm3-22-ΔrliB) were constructed by homologous recombination. The growth cycle of Lm3-22-ΔrliB mutants was slower than that of wild-type Lm3-22. The sensitivity of Lm3-22-ΔrliB to the Listeria phage vB-LmoM-SH3-3 was significantly increased, and the efficiency of plaque formation was enhanced by 128 fold. Compared with wild type, the adhesion and invasion of Lm3-22-ΔrliB decreased significantly (9.3% and 1.33%, respectively). After 4 hours of infection, the proliferation of Lm3-22-ΔrliB in RAW264.7 cells also decreased significantly. Transcription level of invasion-related surface proteins showed that the internalin genes lmo0610 and lm0514, and the peptidoglycan binding protein gene lmo1799 in Lm3-22-ΔrliB were significantly increased. In addition, after interaction with phage, the transcription levels of inlA, lmo0610, lmo1799, lmo2085, and lmo0514 in Lm3-22-ΔrliB cells were significantly upregulated, while inlB was downregulated, compared with Lm3-22 control group with phage treatment. Therefore, rliB deletion effectively regulated the interaction between Listeria and phage, weaken its invasion ability, and provided a new theoretical basis for biocontrol of phage.

Background. Atrial fibrillation (AF) is a common, sustained cardiac arrhythmia. Recent studies have reported an association between ZFHX3/PRRX1 polymorphisms and AF. In this study, a meta-analysis was conducted to confirm these associations. Objective and Methods. The PubMed, Embase, and Wanfang databases were searched, covering all publications before July 20, 2020. Results. Overall, seven articles including 3,674 cases and 8,990 healthy controls for ZFHX3 rs2106261 and 1045 cases and 1407 controls for PRRX1 rs3903239 were included. The odds ratio (OR) (95% confidence interval (CI)) was used to assess the associations. Publication bias was calculated using Egger’s and Begg’s tests. We found that the ZFHX3 rs2106261 polymorphism increased AF risk in Asians (for example, allelic contrast: OR [95% CI]: 1.39 [1.31–1.47], P

Flavor is an important quality of mature tomato fruits. Compared with heirloom tomatoes, modern commercial tomato cultivars are considerably less flavorful. This study aimed to compare the flavor of 71 tomato accessions (8 pink cherry, PC; 11 red cherry, RC; 15 pink large-fruited, PL; and 37 red large-fruited, RL) using hedonism scores and odor activity values. Taste compounds were detected using high-performance liquid chromatography. Volatiles were detected using gas chromatography–olfactometry–mass spectrometry. The flavor of tomato accessions can be evaluated using the DTOPSIS analysis method. According to the results of DTOPSIS analysis, 71 tomato accessions can be divided into 4 classes. Tomato accessions PL11, PC4, PC2, PC8, RL35, RC6, and RC10 had better flavor; accessions PC4, PC8, RC10, RL2, and RL35 had better tomato taste; and accessions PL11, PC2, and RC6 had better tomato odor. The concentrations of total soluble solids, fructose, glucose, and citric acid were shown to positively contribute to tomato taste. Tomato odor was mainly derived from 15 volatiles, namely, 1-hexanol, (Z)-3-hexen-1-ol, hexanal, (E)-2-hexenal, (E)-2-heptenal, (E)-2-octenal, (E,E)-2,4-decadienal, (Z)-3,7-dimethyl-2,6-octadieal, 2,6,6-timethyl-1-cyclohexene-1-carboxaldehyde, (2E)-3-(3-pentyl-2-oxiranyl)acrylaldehyde, 6-methyl-5-hepten-2-one, (E)-6,10-dimetyl-5,9-undecadien-2-one, methyl salicylate, 4-allyl-2-methoxyphenol, and 2-isobutylthiazole. Significant positive correlations (P < 0.05) were detected between the compound concentrations and flavor scores. The above-mentioned compounds can be used as parameters for the evaluation of flavor characteristics and as potential targets to improve the flavor quality of tomato varieties.

The momentous discovery of phagocytic activity in teleost B cells has caused a dramatic paradigm shift from the belief that phagocytosis is performed mainly by professional phagocytes derived from common myeloid progenitor cells, such as macrophages/monocytes, neutrophils, and dendritic cells. Recent advances on phagocytic B cells and their microbicidal ability in teleost fish position B cells at the crossroads, bridging innate with adaptive immunity. Most importantly, an increasing body of experimental evidence demonstrates that, in both teleosts and mammals, phagocytic B cells can recognize, take up, and destroy particulate antigens and then present those processed antigens to CD4+ T cells to elicit adaptive immune responses and that the phagocytosis is mediated by pattern recognition receptors and involves multiple cytokines. Thus, current findings collectively indicate that teleost phagocytic B cells, as well as their counterpart mammalian B1-B cells, can be considered one kind of professional phagocyte. The aim of this review is to summarize recent advances regarding teleost phagocytic B cells, with a particular focus on the recognizing receptors and modulating mechanisms of phagocytic B cells and the process of antigen presentation for T-cell activation. We also attempt to provide new insights into the adaptive evolution of the teleost fish phagocytic B cell on the basis of its innate and adaptive roles.

Clostridium perfringens is an important pathogen for both humans and animals, causing human foodborne disease and necrotic enteritis in poultry. In the present study, a C. perfringens-specific phage, vB_CpeS_BG3P (designated as BG3P hereafter), was isolated from chicken farm sewage. Both electron microscopy and phylogenetic analysis suggested that phage BG3P is a novel phage belonging to Siphoviridae family. Phage BG3P exhibited a broad host range against different C. perfringens isolates (90.63% of strains were infected). Sequencing of the complete genome revealed a linear double-stranded DNA (43,528 bp) with 28.65% GC content. After sequence analysis, 73 open reading frames (orfs) were predicted, of which only 13 were annotated with known functions. No tRNA and virulence encoding genes were detected. It should be noted that the protein of orf 15 has 97.92% homology to C. perfringens-specific chloramphenicol resistance protein, which has not been reported for any C. perfringens phage. Phylogenetic analysis of the ssDNA binding protein demonstrated that this phage is closely related to C. perfringens phages phiSM101 and phi3626. In considering future use as an antimicrobial agent, some biological characteristics were observed, such as a good pH (3–11) stability and moderate temperature tolerance (C. perfringens liquid cultures. Thus, phage treatment with MOI ≥ 100 completely inhibited bacterial growth compared to untreated cultures. Although phage BG3P shows good lytic efficiency and broad host range in vitro, future development and application may need to consider removal of the chloramphenicol-like resistance gene or exploring its lysin for future antibacterial applications.

The recent discovery of long-lived plasma cells (LLPCs) in mammals, which provide a constant expression of specific high-affinity antibodies that mediate humoral memory, has caused a dramatic paradigm shift in the study of immunity and vaccine development. In teleost fish, there are few studies regarding the association between LLPCs and antibody production, and the affinity of the antibodies secreted by the LLPCs is poorly understood. In the present study, channel catfish (Ictalurus punctatus) were immunized with trinitrophenylated-keyhole limpet hemocyanin (TNP-KLH) to examine TNP-specific antibody titers, affinities, antibody-secreting cell (ASC) dynamic changes, and especially the affinity of secreted antibodies by LLPCs post-immunization. We demonstrated that TNP-specific LLPCs were generated starting at week 4 post-immunization, achieved a maximal number at week 8, and maintained a comparable level throughout the 18-week post-immunization period, which was correlated with the dynamics of serum antibody titers and affinity maturation in the response. The LLPCs appeared to mostly reside within, or migrate to, the anterior kidney (bone marrow-like tissue in mammals), but a small portion was also located in the spleen and peripheral blood. The antibodies produced by the LLPCs possessed high affinities, indicating that the generation and development of LLPCs were driven by affinity selection in teleosts. Collectively, the results of this study provide insights toward the evolutionary understanding of the affinity-dependent mechanism of LLPC generation and development.

Teleost B cells have phagocytic activities for ingesting particulate antigens, such as bacteria, in addition to the functional secretion of immunoglobulins (Igs). In the present study, the phagocytic activities of IgM+ B cells under various differentiational conditions residing in peripheral blood leukocytes were investigated in a teleost fish Nile tilapia (Oreochromis niloticus). The IgM+ B cells were recognized as IgMlo or IgMhi subsets based on their membrane IgM (mIgM) levels. The mIgM, secreted IgM (sIgM), major histocompatibility complex class II and reactive oxygen species were detected. Expressions of transcription factors (Pax5 and Blimp-1) and B cell signaling molecules (CD79a, CD79b, BLNK, and LYN) suggested that IgMlo B cells were resembling as plasma-like cells and IgMhi resembling as naïve/mature B cells, respectively. Analysis of phagocytic activities demonstrated that both IgMlo and IgMhi B cells have a similar phagocytic ability (phagocytosis percentage); however, the phagocytic capacity [phagocytic index and the mean fluorescence intensity (MFI)] of IgMhi B cells was significantly higher than that of IgMlo B cells. Taken together, the results indicated that B cell differentiation may cause the decrease of phagocytic capacity but not phagocytic ability of phagocytic IgM+ B cells in teleost. The finding may provide an evolutionary evidence for understanding the greater specialization of the B cell in more sophisticated adaptive humoral immunity, by decreasing phagocytic activity in order to contribute its function more specifically into antibody-secreting.

Tin oxide quantum dots were synthesized in aqueous solution via a simple hydrolysis and oxidation process. The morphology observation showed that the quantum dots had an average grain size of 2.23 nm. The rutile phase SnO2 was confirmed by the structural and compositional characterization. The fluorescence spectroscopy of quantum dots was used to detect the heavy metal ions of Cd2+, Fe3+, Ni2+ and Pb2+, which caused the quenching effect of photoluminescence. The quantum dots showed the response of 2.48 to 100 ppm Ni2+. The prepared SnO2 quantum dots exhibited prospective in the detection of heavy metal ions in contaminated water, including deionized water, deionized water with Fe3+, reclaimed water and sea water. The limit of detection was as low as 0.01 ppm for Ni2+ detection. The first principle calculation based on the density function theory demonstrated the dependence of fluorescence response on the adsorption energy of heavy metal ions as well as ion radius. The mechanism of fluorescence response was discussed based on the interaction between Sn vacancies and Ni2+ ions. A linear correlation of fluorescence emission intensity against Ni2+ concentration was obtained in the logarithmic coordinates. The density of active Sn vacancies was the crucial factor that determined fluorescence response of SnO2 QDs to heavy metal ions.

BACKGROUND:Liver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antigens (SEA) of Schistosoma japonicum promoted the senescence of HSCs via STAT3/P53/P21 pathway. In this paper, our study was aimed to explore whether there are other signaling pathways in the process of SEA-induced HSCs aging and the underlying effect of SKP2/P27 signal on senescent HSCs. METHODOLOGY/PRINCIPAL FINDINGS:Human hepatic stellate cell line, LX-2 cells, were cultured and stimulated with SEA. Western blot and cellular immunofluorescence analysis were performed to determine the expression of senescence-associated protein, such as P27, SKP2 and FoxO3a. Besides, RNA interfering was applied to knockdown the expression of related protein. The senescence of HSCs was determined by senescence-associated β-gal staining. We found that SEA increased the expression of P27 protein, whereas it inhibited the expression of SKP2 and FoxO3a. Knockdown of P27 as well as overexpression of SKP2 both suppressed the SEA-induced senescence of HSCs. In addition, the nuclear translocation of FoxO3a from the nucleus to the cytoplasm was induced by SEA stimulation. CONCLUSIONS/SIGNIFICANCE:The present study demonstrates that SEA promotes HSCs senescence through the FoxO3a/SKP2/P27 pathway.

The influence of oxygen vacancy behaviors during a cooling process in semiconductor gas sensors is discussed by the numerical analysis method based on the gradient-distributed oxygen vacancy model. A diffusion equation is established to describe the behaviors of oxygen vacancies, which follows the effects of diffusion and exclusion in the cooling process. Numerical analysis is introduced to find the accurate solutions of the diffusion equation. The solutions illustrate the oxygen vacancy distribution profiles, which are dependent on the cooling rate as well as the temperature interval of the cooling process. The gas-sensing characteristics of reduced resistance and response are calculated. Both of them, together with oxygen vacancy distribution, show the grain size effects and the re-annealing effect. It is found that the properties of gas sensors can be controlled or adjusted by the designed cooling process. The proposed model provides a possibility for sensor characteristics simulations, which may be beneficial for the design of gas sensors. A quantitative interpretation on the gas-sensing mechanism of semiconductors has been contributed.

The epithelial-mesenchymal transition (EMT) induced by EGF promotes cervical cancer progression; however, the mechanisms underlying the EGF-induced EMT remain unclear. In this study, we reported that miR155 overexpression suppressed EGF-induced EMT, decreased migration/invasion capacities, inhibited cell proliferation and increased the chemo-sensitivity to DDP in human Caski cervical cancer cells. Further, the overexpression of miR155 increased TP53 expression but reduced SMAD2, and CCND1 expression levels. These data suggest that miR155 negatively regulates EGF-induced EMT. We conclude that miR155 does not act as an oncogene but as a tumour suppressor in Caski cells.