DNA Damage-driven Inflammatory Cytokines: Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy.

DNA damage occurs across tumorigenesis and tumor development. Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment (TIME) and dominate tumor progression. Accumulating evidence documents that multiple signaling pathways, including cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein (ATM/ATR), are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines. These cytokines possess multifaced functions in the anti-tumor immune response. Thus, it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines, critical for the development of effective tumor therapies. This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines. We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

Molecular mechanism of different flower color formation of Cymbidium ensifolium.

Cymbidium ensifolium is one of the national orchids in China, which has high ornamental value with changeable flower colors. To understand the formation mechanism of different flower colors of C. ensifolium, this research conducted transcriptome and metabolome analyses on four different colored sepals of C. ensifolium. Metabolome analysis detected 204 flavonoid metabolites, including 17 polyphenols, 27 anthocyanins, 75 flavones, 34 flavonols, 25 flavonoids, 18 flavanones, and 8 isoflavones. Among them, purple-red and red sepals contain a lot of anthocyanins, including cyanidin, pelargonin, and paeoniflorin, while yellow-green and white sepals have less anthocyanins detected, and their metabolites are mainly flavonols, flavanones and flavonoids. Transcriptome sequencing analysis showed that the expression levels of the anthocyanin biosynthetic enzyme genes in red and purple-red sepals were significantly higher than those in white and yellow-green sepals of C. ensifolium. The experimental results showed that CeF3'H2, CeDFR, CeANS, CeF3H and CeUFGT1 may be the key genes involved in anthocyanin production in C. ensifolium sepals, and CeMYB104 has been proved to play an important role in the flower color formation of C. ensifolium. The results of transformation showed that the CeMYB104 is involved in the synthesis of anthocyanins and can form a purple-red color in the white perianth of Phalaenopsis. These findings provide a theoretical reference to understand the formation mechanism of flower color in C. ensifolium.

Genome-Wide Identification and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Cymbidium ensifolium.

The basic helix-loop-helix (bHLH) transcription factors are widely distributed across eukaryotic kingdoms and participate in various physiological processes. To date, the bHLH family has been identified and functionally analyzed in many plants. However, systematic identification of bHLH transcription factors has yet to be reported in orchids. Here, 94 bHLH transcription factors were identified from the Cymbidium ensifolium genome and divided into 18 subfamilies. Most CebHLHs contain numerous cis-acting elements associated with abiotic stress responses and phytohormone responses. A total of 19 pairs of duplicated genes were found in the CebHLHs, of which 13 pairs were segmentally duplicated genes and six pairs were tandemly duplicated genes. Expression pattern analysis based on transcriptome data revealed that 84 CebHLHs were differentially expressed in four different color sepals, especially CebHLH13 and CebHLH75 of the S7 subfamily. The expression profiles of CebHLH13 and CebHLH75 in sepals, which are considered potential genes regulating anthocyanin biosynthesis, were confirmed through the qRT-PCR technique. Furthermore, subcellular localization results showed that CebHLH13 and CebHLH75 were located in the nucleus. This research lays a foundation for further exploration of the mechanism of CebHLHs in flower color formation.

Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation.

OBJECTIVE: Kidney renal clear cell carcinoma (KIRC) is a common renal malignancy that has a poor prognosis. As a member of the F box family, cyclin F (CCNF) plays an important regulatory role in normal tissues and tumors. However, the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear. METHODS: Bioinformatics methods were used to analyze The Cancer Genome Atlas (TCGA) database to obtain gene expression and clinical prognosis data. The CCK8 assay, EdU assay, and xenograft assay were used to detect cell proliferation. The cell senescence and potential mechanism were assessed by SA-ß-gal staining, Western blotting, as well as ELISA. RESULTS: Our data showed that CCNF was highly expressed in KIRC patients. Meanwhile, downregulation of CCNF inhibited cell proliferation in vivo and in vitro. Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1 (CDK1), increasing the proinflammatory factors interleukin (IL)-6 and IL-8, and then enhancing the expression of p21 and p53. CONCLUSION: We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence. Therefore, CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance.

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.

Two new iridoid glycosides from Odontites vulgaris.

Two new iridoid glycosides, named 3'-O-benzoyl-dolichocymboside D (1) and dolichocymboside E (2), along with ten known glycosides (3-12), were isolated from the ethanol extract of the whole plants of Odontites vulgaris Moench. The structures of the isolated compounds were elucidated by 1D and 2D NMR and HR-ESI-MS spectra and by comparison with those reported in the literature. This is the first report on compounds 11 and 12 isolated from the family Scrophulariaceae, and compounds 8-10 were isolated from the genus Odontites.

[Effect of Biantie pretreatment on serum level of PHD2/HIF-1α and brain tissue damage in rats during acute hypobaric hypoxia exposure].

OBJECTIVE: To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. METHODS: Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. RESULTS: Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). CONCLUSION: Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.

[Spatial distribution and correlation of dominant species of karst secondary forest in central Guizhou, China]. / é»”ä¸­å–€æ–¯ç‰¹æ¬¡ç”Ÿæž—ä¼˜åŠ¿ç‰©ç§ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠå ³è”æ€§.

We analyzed the spatial distribution pattern and correlation of the top four dominant tree species in a 2 hm2 karst secondary forest plot of Tianlong Mountain in central Guizhou, using pairwise correlation function g(r) combined with a completely random model (CSR). The results showed that the diameter structure of trees followed an inverted J-shape, and that more trees belonged to diameter class Ⅴ (≥10 cm) driven by the dominant trees of Lithocarpus confinis and Platycarya longipes. L. confinis presented an inverted J-shaped distribution, and the population could renew very well and was in the primary growth stage. The abundance of P. longipes and Itea yunnanensis increased gradually with increasing diameter class. The density of grown and large trees was far more than the young and small individuals, which indicated poor population regeneration, and the population was in the middle and late growth stages. The top dominant tree species, except L. confinis, showed clustering distribution at large scale, which was decreased gradually with scale and trended to distribute randomly. The pattern was particularly prominent in the diameter class for young trees. Different diameter classes of different tree species presented diffe-rent spatial distribution patterns which influenced by many factors. In terms of interspecific associations, the four dominant tree species showed negative or no associations. The higher importance value of tree species, the lower the degree of association with other dominant species. The two negative correlation tree species had the lowest degree of correlation at small scale. With the increase of spatial scale, the degree of negative correlation decreased gradually, and tended to be no correlation.

One novel naphthalene derivative and other constituents with anti-complementary activities from the aerial parts of Dracocephalum moldavica.

One novel naphthalene derivative, 2-octa-2',4',6'-atriynenaphthalene (1), together with eighteen known compounds (2-19) were isolated from the aerial parts of Dracocephalum moldavica L. Compounds 2, 8, 10, 13, 15-17 and 19 were obtained from the family Lamiaceae for the first time, and compounds 11 and 18 were firstly identified from the genus of Dracocephalum. All the isolates were evaluated for anti-complementary activities through the classical and alternative pathways, and the targets of the most active compounds on the complement activation cascade were also investigated.

NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury.

Acute kidney injury (AKI) with maladaptive tubular repair leads to renal fibrosis and progresses to chronic kidney disease (CKD). At present, there is no curative drug to interrupt AKI-to-CKD progression. The nuclear factor of the activated T cell (NFAT) family was initially identified as a transcription factor expressed in most immune cells and involved in the transcription of cytokine genes and other genes critical for the immune response. NFAT2 is also expressed in renal tubular epithelial cells (RTECs) and podocytes and plays an important regulatory role in the kidney. In this study, we investigated the renoprotective effect of 11R-VIVIT, a peptide inhibitor of NFAT, on renal fibrosis in the AKI-to-CKD transition and the underlying mechanisms. We first examined human renal biopsy tissues and found that the expression of NFAT2 was significantly increased in RTECs in patients with severe renal fibrosis. We then established a mouse model of AKI-to-CKD transition using bilateral ischemia-reperfusion injury (Bi-IRI). The mice were treated with 11R-VIVIT (5 mg/kg, i.p.) on Days 1, 3, 10, 17 and 24 after Bi-IRI. We showed that the expression of NFAT2 was markedly increased in RTECs in the AKI-to-CKD transition. 11R-VIVIT administration significantly inhibited the nuclear translocation of NFAT2 in RTECs, decreased the levels of serum creatinine and blood urea nitrogen, and attenuated renal tubulointerstitial fibrosis but had no toxic side effects on the heart and liver. In addition, we showed that 11R-VIVIT administration alleviated RTEC apoptosis after Bi-IRI. Consistently, preapplication of 11R-VIVIT (100 nM) and transfection with NFAT2-targeted siRNA markedly suppressed TGFß-induced HK-2 cell apoptosis in vitro. In conclusion, 11R-VIVIT administration inhibits IRI-induced NFAT2 activation and prevents AKI-to-CKD progression. Inhibiting NFAT2 may be a promising new therapeutic strategy for preventing renal fibrosis after IR-AKI.

Genome-Wide Identification of the MYB Gene Family in Cymbidiumensifolium and Its Expression Analysis in Different Flower Colors.

MYB transcription factors of plants play important roles in flavonoid synthesis, aroma regulation, floral organ morphogenesis, and responses to biotic and abiotic stresses. Cymbidium ensifolium is a perennial herbaceous plant belonging to Orchidaceae, with special flower colors and high ornamental value. In this study, a total of 136 CeMYB transcription factors were identified from the genome of C. ensifolium, including 27 1R-MYBs, 102 R2R3-MYBs, 2 3R-MYBs, 2 4R-MYBs, and 3 atypical MYBs. Through phylogenetic analysis in combination with MYB in Arabidopsis thaliana, 20 clusters were obtained, indicating that these CeMYBs may have a variety of biological functions. The 136 CeMYBs were distributed on 18 chromosomes, and the conserved domain analysis showed that they harbored typical amino acid sequence repeats. The motif prediction revealed that multiple conserved elements were mostly located in the N-terminal of CeMYBs, suggesting their functions to be relatively conserved. CeMYBs harbored introns ranging from 0 to 13 and contained a large number of stress- and hormone-responsive cis-acting elements in the promoter regions. The subcellular localization prediction demonstrated that most of CeMYBs were positioned in the nucleus. The analysis of the CeMYBs expression based on transcriptome data showed that CeMYB52, and CeMYB104 of the S6 subfamily may be the key genes leading to flower color variation. The results lay a foundation for the study of MYB transcription factors of C. ensifolium and provide valuable information for further investigations of the potential function of MYB genes in the process of anthocyanin biosynthesis.

Development of an UPLC-MS/MS Method for the Quantitative Analysis of Upadacitinib in Beagle Dog Plasma and Pharmacokinetics Study.

BACKGROUND: Upadacitinib, a novel selective Janus kinase 1 (JAK1) inhibitor, has been recently approved by the US FDA for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantitative analysis of upadacitinib in beagle dog plasma was developed and validated. METHODS: Upadacitinib and fedratinib (internal standard, IS) were extracted with ethyl acetate under alkaline condition and then separated and detected. The chromatographic column was Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm), the mobile phase was acetonitrile and 0.1% formic acid in water with gradient elution procedure, and the flow rate was 0.40 mL/min. Under the positive ion mode, upadacitinib and IS were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 447.00 → 361.94 for upadacitinib and m/z 529.82 → 141.01 for IS. RESULTS: In the concentration range of 1-500 ng/mL, upadacitinib had good linearity, and the lower limit of quantification (LLOQ) was 1 ng/mL. The RSD of the intra- and inter-day precision was less than 10.03%, and the RE of accuracy was -3.79% to 2.58%. The extraction recovery of upadacitinib was more than 80%, the matrix effect was around 100%, and upadacitinib was found to be stable. CONCLUSION: The novel optimized UPLC-MS/MS assay was an effective tool for the determination of upadacitinib and had been successfully applied to the pharmacokinetic study of upadacitinib in beagle dogs, and this method would also be used to study DDIs.

Echinacea Purpurea Extract (cichoric Acid) Exerts an Anti-inflammatory Effect on Yak PBMCs and Regulates the TLR4 Signalling Pathway.

INTRODUCTION: Inflammation is one of the main causes of impaired health in livestock and some of its processes weaken animal productivity and impact human health. The present study was conducted to evaluate the effect of echinacea extract (cichoric acid - CA) on yak peripheral blood mononuclear cells (PBMCs), inflammatory-related factors, and the toll-like receptor (TLR)4 signalling pathway induced by lipopolysaccharide (LPS) in these PBMCs. MATERIAL AND METHODS: Yak PBMCs were co-cultured with LPS and CA in vitro. The proliferative activity of cells was detected using the cell-counting kit-8 method, the optimal stimulation concentration of LPS was selected, the effect of CA on the content of inflammation-related factors was evaluated using an ELISA kit, and the mRNA expression of these factors was detected by RT-PCR. RESULTS: CA inhibited the inflammatory response of yak PBMCs induced by LPS. CA inhibited gene and protein expression of key nodes of the TLR4 signalling pathway in yak PBMCs. CONCLUSION: It is suggested that CA has anti-inflammatory and immunomodulatory effects on yak PBMCs via the TLR4 pathway.

6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy.

Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.

Cichoric acid from extracted Echinacea purpurea induces the proliferation and apoptosis of peripheral blood mononuclear cells from yaks

BACKGROUND: Cichoric acid (CA) is extracted from Echinacea purpurea. It is well known and widely used for its immunological function. However, the effect of CA on peripheral blood mononuclear cells (PBMCs) from yaks is still unclear. This study investigated the potential influences of CA on the proliferation, cytokine induction, and apoptosis of PBMCs from Datong yak in vivo, and aimed to provide a basis for exploring the pharmacological activities of CA on yaks. RESULTS: In this study, CA promoted PBMCs proliferation by combining concanavalin A (Con A) and exhibited a dose-dependent effect as demonstrated by a Cell Counting Kit-8. The concentration of 60 µg/ml CA was the best and promoted the transformation from the G0/G1 phase to the S and G2/M phases with Con A. Furthermore, 60 µg/ml CA significantly increased IL-2, IL-6, and IFN-γ levels and PCNA, CDK4 and Bcl-2 expression levels, but it significantly inhibited the TP53, Bax, and Caspase-3 expression levels. Transcriptome analysis revealed a total of 6807 differentially expressed genes (DEGs) between the CA treatment and control groups. Of these genes, 3788 were significantly upregulated and 3019 were downregulated. Gene Ontology and pathway analysis revealed that DEGs were enriched in cell proliferation and immune function signaling pathways. The expression level of some transcription factors (BTB, Ras, RRM_1, and zf-C2H2) and genes (CCNF, CCND1, and CDK4) related to PBMCs proliferation in yaks were significantly promoted after CA treatment. By contrast, anti-proliferation-associated genes (TP53 and CDKN1A) were inhibited. CONCLUSIONS: In summary, CA could regulate the immune function of yaks by promoting proliferation and inhibiting inflammation and apoptosis of PBMCs.

Is Social Media Use Changing Who We Are? Examining the Bidirectional Relationship Between Personality and Social Media Use.

Social media has changed the way we live. It is now so integral to daily life that it is one of the top activities that people spend their time on each day. Given its ubiquity, it is important to understand what kinds of personality traits draw people toward social media and whether social media changes personality. The present study utilizes a longitudinal design with a large nationally representative sample (N = 11,629) to examine the bidirectional relationship between personality and social media use (SMU). First, cross-lagged analyses revealed a bidirectional relationship between SMU and neuroticism such that neuroticism predicted increased SMU, but SMU also predicted increased neuroticism. However, while increased SMU predicted reduced honesty/humility, honesty/humility did not predict SMU. No other relationships emerged between personality and SMU. This study is the first to examine the extent to which personality both predicts SMU, and is in turn reciprocally shaped by social media exposure in a large-scale national probability panel study.

Baicalin Inhibits Coxsackievirus B3 Replication by Reducing Cellular Lipid Synthesis.

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.

How Common Is Cyberbullying Among Adults? Exploring Gender, Ethnic, and Age Differences in the Prevalence of Cyberbullying.

Previous research on cyberbullying has almost entirely focused on examining its prevalence among teens and young adults leaving it unclear how prevalent it is within the wider population. The present study used a New Zealand (NZ) national sample (N = 20,849) to examine gender, age, and ethnic differences in the experiences of cyberbullying victimization. On average, nearly 14.9 percent of respondents stated that they have ever been a target of cyberbullying before, with 2.2 percent respondents reporting such experiences within the past month. While young adults (18-25 years) experienced the highest levels of cyberbullying during both time frames (lifetime and past month), the prevalence of cyberbullying was lower among older age cohorts, with the lowest rate among the 66+ age group. Reports of cyberbullying slightly varied among men and women, with women overall reporting slightly greater levels of having ever experienced cyberbullying than men; however, this significant difference did not carry into reports of cyberbullying over the past month. On average, participants identifying as European reported lower levels of cyberbullying than Maori and Pacific Nations participants during both time frames, with Asian participants falling in the middle. Taken together, these findings provide a nuanced understanding of the prevalence of cyberbullying in a large national sample of NZ adults.

Comparison of Breast Cancer Risk Predictive Models and Screening Strategies for Chinese Women.

BACKGROUND: Previous studies have shown that organized mammographic screening implementation in China may not be cost-effective. Our aim was to develop a valid predictive mathematical model for selecting high-risk groups eligible for mammography examinations (MAMs) and cost-effective strategies for breast cancer screening among Chinese women. METHODS: Between 2009 and 2012, 13,355 eligible women aged 30-65 years were enrolled from the community in Chengdu City. All subjects were administered a valid questionnaire and given MAMs. Using biopsies and 1-year follow up, we compared the accuracy indexes of three predictive models (back-propagation artificial neural network [BP-ANN], logistic regression [LR], and Gail) and four serial screening strategies (BP-ANN→MAM, LR→MAM, Gail→MAM, and MAM alone). We also evaluated the benefits of the four strategies by comparing their incidence-adjusted positive predictive value (PPV). All analyses were conducted with three age-based subgroups: 30-39, 40-49, and 50-65. RESULTS: The BP-ANN1, in conjunction with additional continuous risk factor variables, was the best predictive model, with the highest sensitivity (SEN, 76.99%) and specificity (SPE, 54.20%). The BP-ANN1→MAM strategy was best for the 40-49 age group, with the highest adjusted PPV (9.80%) and reasonable SEN (81.82%). CONCLUSION: We found that the BP-ANN model performed the best and was the most accurate for predicting high risk for breast cancer among Chinese women, and the BP-ANN→MAM screening strategy was most effective among the 40-49 age group. However, mammography alone may be a sufficient screening strategy for women aged 50-65.