How is vaping promoted in an illegal market? A qualitative study of Singaporeans' social media encounters.

BACKGROUND: Although Singapore has completely banned vaping, it is heavily promoted on social media. This study explored vaping-related social media content that Singaporeans are exposed to, and how it shapes vaping-related perceptions and experiences in the context of Singapore's strict regulations. METHODS: We held 10 focus group discussions with 63 Singaporeans aged 21-40 years, with diversity by sociodemographics, smoking history, vaping history and self-reported exposure to vaping-related social media content. Participants provided screenshots of any vaping-related content they encountered on their social media. Subsequently, in focus groups, they were shown a variety of this content and asked to discuss. We coded transcripts using inductive methods. RESULTS: Participants had encountered vape advertisements from neighbouring countries featuring attractive products, flavours, celebrity endorsements and entertainment shows, which they found highly appealing. Participants encountered posts that did not overtly advertise vaping but depicted people vaping in social settings, thereby normalising vaping despite its illegal status. They perceived government campaigns to deter vaping as biased and agenda driven, calling for a more nuanced message and use of local influencers and personal stories to communicate the rationale of the vaping regulations to the public. CONCLUSION: Having a law that bans vaping may not be enough; it needs to be complemented with more comprehensive marketing restrictions on social media platforms and effective enforcement of bans on social media promotions from overseas.

Estrogen Receptor Is Required for Metformin-Induced Apoptosis in Breast Cancer Cells Under Hyperglycemic Conditions.

Backgrounds: About 25% to 30% of estrogen receptor (ER)-positive breast cancer patients develop resistance to endocrine therapy. Human epidermal growth factor receptor 2 (HER2) has been shown to cooperate with several growth factors that regulate cellular energy metabolism, including the insulin-like growth factor 1 receptor (IGF-1R). Objective: As the first-line therapy for type 2 diabetes mellitus (T2DM) patients, metformin is widely known to inhibit the metabolic reprogramming of cancer cells. This study aims to investigate metformin's efficacy in inhibiting endocrine resistance related to genes regulating energy metabolism in both ER-positive and ER-negative breast cancer cell lines under hyperglycemic conditions. Design and methods: MDA-MB-361 (ER-positive, HER2-positive) and SKBR3 (ER-negative, HER2-positive) cancer cell lines were used to represent ER status. Cell viability and cell survival rate were measured using the colorimetric assay of Cell Counting Kit-8. All mRNA levels were quantified using real-time quantitative polymerase chain reaction preceded by reverse transcription. A P value of <.05 was considered statistically significant. Results: Unlike MDA-MB-361, SKBR3 were found to acquire resistance upon metformin treatment in hyperglycemic conditions. Moreover, the mRNA expression of IGF-1R and its downstream signaling, such as the mammalian target of rapamycin (mTOR), was not affected by metformin. Meanwhile, the mRNA expression level of ribosomal S6 kinase 1 (S6K1) was upregulated, whereas forkhead box O1 (FOXO1) was downregulated after metformin treatment in hyperglycemic conditions. Conclusions: This preliminary study suggests that an alternative pathway of metformin resistance may exist in the absence of ERα. Therefore, relying solely on metformin may be inadequate to inhibit the aggressiveness of breast cancer cells.

Navigating metformin's impact on breast cancer: insights into resistance, alternative pathways, and the crucial role of estrogen receptor under high-glucose conditions Around 25% to 30% of breast cancer patients with estrogen receptor (ER)-positive tumors become resistant to hormone therapy. This study explores whether metformin, a drug commonly used for type 2 diabetes, can counteract this resistance by affecting genes linked to energy metabolism. The research focused on both ER-positive (MDA-MB-361) and ER-negative (SKBR3) breast cancer cell lines under high-glucose conditions. Results showed that although metformin inhibited the growth of ER-positive cells, it surprisingly promoted resistance in ER-negative cells. The expression of insulin-like growth factor 1 receptor (IGF-1R) and its downstream signals like mammalian target of rapamycin (mTOR) remained unaffected by metformin. However, metformin did alter the expression of other genes related to energy metabolism, suggesting that a different resistance pathway might exist in ER-negative cases. In conclusion, this early study implies that relying solely on metformin might not be sufficient to combat the aggressiveness of breast cancer cells, particularly in cases lacking ERα. More research is needed to understand alternative pathways and develop more effective strategies against resistance.

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

Decoding tumor stage by peritumoral and intratumoral radiomics in resectable esophageal squamous cell carcinoma.

PURPOSE: To evaluate the potential application of radiomics in predicting Tumor-Node-Metastasis (TNM) stage in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study included 122 consecutive patients (mean age, 57 years; 27 women). Corresponding tumor of interest was identified on axial arterial-phase CT images with manual annotation. Radiomics features were extracted from intra- and peritumoral regions. Features were pruned to train LASSO regression model with 93 patients to construct a radiomics signature, whose performance was validated in a test set of 29 patients. Prognostic value of radiomics-predicted TNM stage was estimated by survival analysis in the entire cohort. RESULTS: The radiomics signature incorporating one intratumoral and four peritumoral features was significantly associated with TNM stage. This signature discriminated tumor stage with an area under curve (AUC) of 0.823 in the training set, with similar performance in the test set (AUC 0.813). Recurrence-free survival (RFS) was significantly different between different radiomics-predicted TNM stage groups (Low-risk vs high-risk, log-rank P = 0.004). Univariate and multivariate Cox regression analyses revealed that radiomics-predicted TNM stage was an independent preoperative factor for RFS. CONCLUSIONS: The proposed radiomics signature combing intratumoral and peritumoral features was predictive of TNM stage and associated with prognostication in ESCC.

Nutrition and Physical Activity Counseling by General Practitioners in China.

Introduction: To reduce unhealthy lifestyles in China, it is critical to implement effective strategies. Counseling provided by physicians is important for assisting patients in improving their lifestyles, and general practitioners (GPs) are the main providers of lifestyle counseling to patients. However, few studies have focused on the lifestyle counseling practices by GPs in China, particularly in regard to nutrition and physical activity. Objective: The aims of this study are: (i) to examine the current practice of Chinese GPs in counseling patients regarding nutrition and physical activity; (ii) to understand the common barriers to such counseling by Chinese GPs; and (iii) to study the association between GPs' personal lifestyle choices and their practices in lifestyle counseling. Methods: A cross-sectional, self-reported online questionnaire was conducted among GPs in Hunan province, China. A total of 198 GPs completed the questionnaire. Results: The majority of GPs provide nutrition and physical activity counseling to less than 40% of their patients, spending less than three minutes per counseling session. The main reported barriers to counseling on nutrition and physical activity are inadequate time and a lack of knowledge or experience. GPs primarily acquire knowledge through medical books and journals, followed by science popularization. Furthermore, GPs who maintain healthier lifestyle habits, possess a better understanding of lifestyle guidelines, conduct longer office visits, and exhibit higher self-efficacy are more likely to provide counseling to patients. Conclusion: This study highlights the need for improvement in nutrition and physical activity counseling among Chinese GPs. GPs' personal nutrition and physical activity habits may measurably influence their counseling practice. We recommend that GPs themselves adopt healthier lifestyle habits to potentially improve their counseling practice. Moreover, proactive measures should be taken to assist GPs in overcoming barriers encountered with lifestyle counseling.

Effects of varying dietary folic acid during weaning stress of piglets.

The present study was conducted to evaluate the effect of dietary folic acid on the growth performance, intestinal morphology, and intestinal epithelial cells renewal in post-weaning piglets. Twenty-eight piglets (weaned at day 21, initial body weight of 6.73 ± 0.62 kg) were randomly allotted to 4 treatments with 7 pens per diet and 1 piglet per pen. The piglets were fed the same antibiotic-free and zinc oxide-free basal diets supplemented with folic acid at 0, 3, 9, and 18 mg/kg for 14 days. The results showed that dietary supplementation with folic acid increased villus height (VH) (P = 0.003; linear, P = 0.001), VH-to-crypt depth (VH:CD) ratio (P = 0.002; linear, P = 0.001), villus surface area (VSA) (P = 0.026; linear, P = 0.010). The analyzed parameters ADG, serum urea nitrogen (BUN) content, VH, VSA, and serum folate (SF) concentration responded linearly to the dietary folic acid concentration when the dietary folic acid concentration was below 4.42, 5.26, 4.79, 3.47, and 3.53 mg/kg respectively (R 2  = 0.995, 0.995, 0.999, 0.999, 0.872, P = 0.09, 0.07, 0.09, 0.09, 0.36, respectively), as assessed by a two-linear broken-line regression. Above these breakpoints, the response of ADG, VH, VSA, and SF plateaued in response to changes in dietary folic acid concentration. Moreover, dietary supplementation with folic acid significantly increased the lactase (P = 0.001; linear, P = 0.001) and sucrase activities (P = 0.021; linear, P = 0.010) in the jejunal mucosa of weaned piglets. The mRNA expression of solute carrier family 6 member 19 (SLC6a19), solute carrier family 1 member 1 (SLC7a1), tumor necrosis factor-α (TNF-α), the number of Ki67 positive cells, and cell shedding rate had a significant linear contrast (P = 0.023, 0.021, 0.038, 0.049, and 0.008, respectively) in dietary folic acid groups. In conclusion, our results indicate that folic acid supplementation can improve the growth performance and intestinal morphology of weaned piglets by maintaining the balance of epithelial cell renewal.

Prediction of microvascular invasion in solitary hepatocellular carcinoma ≤ 5 cm based on computed tomography radiomics.

BACKGROUND: Liver cancer is one of the most common malignant tumors, and ranks as the fourth leading cause of cancer death worldwide. Microvascular invasion (MVI) is considered one of the most important factors for recurrence and poor prognosis of liver cancer. Thus, accurately identifying MVI before surgery is of great importance in making treatment strategies and predicting the prognosis of patients with hepatocellular carcinoma (HCC). Radiomics as an emerging field, aims to utilize artificial intelligence software to develop methods that may contribute to cancer diagnosis, treatment improvement and evaluation, and better prediction. AIM: To investigate the predictive value of computed tomography radiomics for MVI in solitary HCC ≤ 5 cm. METHODS: A total of 185 HCC patients, including 122 MVI negative and 63 MVI positive patients, were retrospectively analyzed. All patients were randomly assigned to the training group (n = 124) and validation group (n = 61). A total of 1351 radiomic features were extracted based on three-dimensional images. The diagnostic performance of the radiomics model was verified in the validation group, and the Delong test was applied to compare the radiomics and MVI-related imaging features (two-trait predictor of venous invasion and radiogenomic invasion). RESULTS: A total of ten radiomics features were finally obtained after screening 1531 features. According to the weighting coefficient that corresponded to the features, the radiomics score (RS) calculation formula was obtained, and the RS score of each patient was calculated. The radiomics model exhibited a better correction and identification ability in the training and validation groups [area under the curve: 0.72 (95% confidence interval: 0.58-0.86) and 0.74 (95% confidence interval: 0.66-0.83), respectively]. Its prediction performance was significantly higher than that of the image features (P < 0.05). CONCLUSION: Computed tomography radiomics has certain predictive value for MVI in solitary HCC ≤ 5 cm, and the predictive ability is higher than that of image features.

Integrative Multi-Omics Analysis Reveals Candidate Biomarkers for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Due to the lack of early detection and treatment, the survival rate of OSCC remains poor and the incidence of OSCC has not decreased during the past decades. To explore potential biomarkers and therapeutic targets for OSCC, we analyzed differentially expressed genes (DEGs) associated with OSCC using RNA sequencing technology. Methylation-regulated and differentially expressed genes (MeDEGs) of OSCC were further identified via an integrative approach by examining publicly available methylomic datasets together with our transcriptomic data. Protein-protein interaction (PPI) networks of MeDEGs were constructed and highly connected hub MeDEGs were identified from these PPI networks. Subsequently, expression and survival analyses of hub genes were performed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) online tool. A total of 56 upregulated MeDEGs and 170 downregulated MeDEGs were identified in OSCC. Eleven hub genes with high degree of connectivity were picked out from the PPI networks constructed by those MeDEGs. Among them, the expression level of four hub genes (CTLA4, CDSN, ACTN2, and MYH11) were found to be significantly changed in the head and neck squamous carcinoma (HNSC) patients. Three hypomethylated hub genes (CTLA4, GPR29, and TNFSF11) and one hypermethylated hub gene (ISL1) were found to be significantly associated with overall survival (OS) of HNSC patients. Therefore, these hub genes may serve as potential DNA methylation biomarkers and therapeutic targets of OSCC.

Use of Vaginal Reconstructive Surgery in Cervical Cancer Patients to Prevent Vaginal Stump Contracture.

PURPOSE: The life quality of cervical cancer patients is severely compromised due to the vaginal stump contracture after surgery combined with radiotherapy. Therefore, our study focuses on ameliorating or preventing postoperative vaginal contracture. The objectives of this study were (1) to evaluate the method of ileal graft with vascular pedicle to extend the length of vagina and (2) to investigate the effect of the operation to prevent vaginal stump contracture after cervical cancer surgery combined with radiotherapy. METHODS: Twenty-five patients with vaginal stump contracture after cervical cancer radical resection with sequential radiotherapy were recruited for the study between 2011 and 2014. The therapy includes releasing the adhesion between vaginal stump and rectum as well as bladder, resecting the vaginal stump but reserving the exterior orifice of vagina, and extending the vaginal length using vascularized ileal graft. RESULTS: No postoperative complications such as infection and bleeding were observed in all 25 patients. The patients were satisfied with the length and width of vagina after extension; the discharge of reconstructed vagina was acceptable. All patients had sexual intercourse on the follow-up examination, and five patients complained of vaginal bleeding during or after sexual intercourse, although no abnormality was found on colposcopy. CONCLUSIONS: The patients demonstrated a high level of safety, efficacy, and satisfaction with the ileal-vaginal extension for treating vaginal stump contracture after cervical cancer surgery combined with radiotherapy, suggesting that this method is valid for broad clinical application to improve the life quality of cervical cancer patients after surgery.

Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factors.

Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1ß, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/ß2-glycoprotein I (oxLDL/ß2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr -/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1ß) and hepatic (TNF-α, IL-1α, IL-1ß) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis.

Cytotoxic Effects of Alcohol Extracts from a Plastic Wrap (Polyvinylidene Chloride) on Human Cultured Liver Cells and Mouse Primary Cultured Liver Cells.

An increasing accumulation of microplastics and further degraded nanoplastics in our environment is suspected to have harmful effects on humans and animals. To clarify this problem, we tested the cytotoxicity of two types of plastic wrap on human cultured liver cells and mouse primary cultured liver cells. Alcohol extracts from plastic wrap, i.e., polyvinylidene chloride (PVDC), showed cytotoxic effects on the cells. Alcohol extracts of polyethylene (PE) wrap were not toxic. The commercially available PVDC wrap consists of vinylidene chloride, epoxidized soybean oil, epoxidized linseed oil as a stiffener and stabilizer; we sought to identify which component(s) are toxic. The epoxidized soybean oil and epoxidized linseed oil exerted strong cytotoxicity, but the plastic raw material itself, vinylidene chloride, did not. Our findings indicate that plastic wraps should be used with caution in order to prevent health risks.

Current Advances and Limitations of Deep Learning in Anticancer Drug Sensitivity Prediction.

Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a branch of machine learning, is an important aspect of in silico research. Its outstanding computational performance means that it has been used for many biomedical purposes, such as medical image interpretation, biological sequence analysis, and drug discovery. Several studies have predicted anticancer drug sensitivity based on deep learning algorithms. The field of deep learning has made progress regarding model performance and multi-omics data integration. However, deep learning is limited by the number of studies performed and data sources available, so it is not perfect as a pre-clinical approach for use in the anticancer drug screening process. Improving the performance of deep learning models is a pressing issue for researchers. In this review, we introduce the research of anticancer drug sensitivity prediction and the use of deep learning in this research area. To provide a reference for future research, we also review some common data sources and machine learning methods. Lastly, we discuss the advantages and disadvantages of deep learning, as well as the limitations and future perspectives regarding this approach.

[Analysis of differential genes related to dormancy release of Paris polyphylla var. chinensis seeds by transcriptome sequencing].

The study aims at exploring the expression of differential genes and related metabolic pathways in the process of seed dormancy release. The dormant embryo and the dormant released embryo of Paris polyphylla var. chinensis were used as the test materials, a new generation high-throughput sequencing methods to sequence the transcriptome of the samples was used to carry out systematic bioinformatics analysis. We obtained 62 882 650 and 62 263 366 clean reads from the DNA libraries of the samples before and after dormancy breaking. A total of 69 248 differentially expressed genes(DEGs) were obtained, 56 426 up-regulated genes and 12 822 down-regulated genes. There are 138 267 differentially expressed genes in the process of embryo dormancy release, which were annotated by GO function to 58 subclasses of biological processes, molecular functions and cell components. The annotated differentially expressed genes were closely related to metabolic processes, biological regulation, cell component synthesis and enzyme catalytic activity. We found 139 metabolic pathways through pathway analysis of 58 722 differentially expressed genes. Before and after dormancy, DEGs were mainly enriched in carbon metabolism, secondary metabolite biosynthesis and polysaccharide metabolism. Based on the annotation results in KEGG database, we found 16 metabolic pathways related to the dormancy release of P. polyhoylla var. chinensis. A large number of differentially expressed genes were involved in embryo morphogenesis, polysaccharide decomposition and protein synthesis during seed development and dormancy release. It involves the interaction of multiple metabolic pathways and constitutes a complex regulation network for dormancy relief.

Changes in cecal morphology, cell proliferation, antioxidant enzyme, volatile fatty acids, lipopolysaccharide, and cytokines in piglets during the postweaning period.

Weaning stresses often induce markedly structural and functional changes in the small intestine. However, little data are available on the changes of the morphology, function, and health in the cecum of piglets post-weaning. This study was conducted to measure the effects of weaning on the cecum in piglets. Forty piglets were weaned at 21 d and samples were collected at different time points (days 0, 1, 3, 7, and 14) post-weaning. The crypt depth, crypt width, and total epithelial cell numbers increased on days 7 and 14, compared with days 0, 1, and 3 (P < 0.001). The value of Ki67/total epithelial cells was highest on day 0 compared with all other days (P < 0.05). Besides, a higher concentration of malondialdehyde was observed on day 3 (P < 0.001). The activity of CuZn-superoxide dismutase (P < 0.05) enhanced from day 0 to 1 and the activity of catalase increased from day 1 to 3 (P < 0.001). In addition, days 3, 7, and 14 had greater acetic, propanoic, and butyric acid contents than on day 1 (P < 0.001). The pH and monocarboxylate transporter 1 (MCT1) expression increased from day 0 to 1 and from day 3 to 7 and decreased between days 1 and 3 (P < 0.001). The mRNA expression of solute carrier family 9 member A3 (SLC9A3) decreased on day 1 compared to all other postweaning days (P < 0.05). The abundance of toll-like receptor 4 (TLR4) and interferon-γ (IFN-γ) mRNA expression increased (P < 0.05) during the first 24 h after weaning. The concentration of lipopolysaccharide increased from day 3 to 7, then decreased on day 14 (P < 0.05). The mRNA expression of tumor necrosis factor-α (TNF-α) enhanced from day 7 to 14 (P < 0.05). The abundance of phosphorylated mammalian target of rapamycin protein was lower on day 14 than day 0 (P < 0.05). Taken together, these results show that weaning in piglets influences intestinal morphology, function, and health in the cecum.