MiR-26b-3p Promotes Intestinal Motility Disorder by Targeting FZD10 to Inhibit GSK3ß/ß-Catenin Signaling and Induce Enteric Glial Cell Apoptosis.

Enteric glial cells (EGCs) are the major component of the enteric nervous system and affect the pathophysiological process of intestinal motility dysfunction. MicroRNAs (miRNAs) play an important role in regulating gastrointestinal homeostasis. However, the mechanism of miRNA-mediated regulation of EGCs in intestinal dysmotility remains unclear. In this study, we investigated the effect of EGC apoptosis on intestinal dysmotility, and the effect of miR-26b-3p on EGC proliferation and apoptosis in vivo and in vitro. A loperamide hydrochloride (Lop)-induced constipated mouse model and an in vitro culture system of rat EGCs were established. The transcriptome was used to predict the differentially expressed gene miR-26b-3p and the target gene Frizzled 10 (FZD10), and their targeting binding relationship was verified by luciferase. EGCs were transfected with miR-26b-3p mimic or antagomir, and the FZD10 expression was down-regulated by siRNA. Immunofluorescence and flow cytometry were used to detect EGC apoptosis. MiR-26b-3p and FZD10 expressions were examined using quantitative real-time PCR (qRT-PCR). The CCK-8 assay was used to detect EGC proliferation. The protein levels were detected by Western blotting and enzyme-linked immunosorbent assay (ELISA). The results showed that miR-26b-3p was up-regulated in the Lop group, whereas FZD10 was down-regulated, and EGC apoptosis was increased in the colon of intestinal dysmotility mice. FZD10 down-regulation and miR-26b-3p mimic significantly increased glycogen synthase kinase-3ß phosphorylation (p-GSK3ß) levels, decreased ß-catenin expression, and promoted EGC apoptosis. MiR-26b-3p antagomir alleviated intestinal dysmotility, promoted EGC increased activity of EGCs, and reduced EGC apoptosis in vivo. In conclusion, this study indicated that miR-26b-3p promotes intestinal motility disorders by targeting FZD10 to block GSK3ß/ß-catenin signaling and induces apoptosis in EGCs. Our results provide a new research target for the treatment and intervention of intestinal dysmotility.

Developing Transparent and Conductive PolyHEMA Gels Using Deep Eutectic Solvents.

Poly(2-hydroxyethyl methacrylate) (polyHEMA) hydrogels are commonly used in biomaterials such as contact lenses. However, water evaporation from these hydrogels can cause discomfort to wearers, and the bulk polymerization method used to synthesize them often results in heterogeneous microstructures, reducing their optical properties and elasticity. In this study, we synthesized polyHEMA gels using a deep eutectic solvent (DES) instead of water and compared their properties to traditional hydrogels. Fourier-transform infrared spectroscopy (FTIR) showed that HEMA conversion in DES was faster than in water. DES gels also demonstrated higher transparency, toughness, and conductivity, along with lower dehydration, than hydrogels. The compressive and tensile modulus values of DES gels increased with HEMA concentration. A DES gel with 45% HEMA showed excellent compression-relaxation cycles and had the highest strain at break value in the tensile test. Our findings suggest that DES is a promising alternative to water for synthesizing contact lenses with improved optical and mechanical properties. Furthermore, DES gels' conduction properties may enable their application in biosensors. This study presents an innovative approach to synthesizing polyHEMA gels and provides insights into their potential applications in the biomaterials field.

The Association of Influencer Marketing and Consumption of Non-Alcoholic Beer with the Purchase and Consumption of Alcohol by Adolescents.

In this study, we examined influencer marketing and consumption of non-alcoholic beer by adolescents to determine how these factors could affect the intentions of adolescents to purchase and drink alcohol. A total of 3121 high-school students recruited from 36 schools in Taiwan completed a self-administered questionnaire during the COVID-19 pandemic in 2022. The results indicate that 19% of these adolescents consumed non-alcoholic beer and 28% consumed alcohol in the past year. Multivariate analysis positively associated adolescents' exposure to influencer marketing with their purchase and consumption of non-alcoholic beer. Adolescents' exposure to influencer marketing of non-alcoholic beer combined with lower levels of parental restrictive mediation was associated with increased odds of the purchase and consumption of alcohol. For individuals who did not purchase alcohol in the past year, both the exposure to influencer marketing and the consumption of non-alcoholic beer were associated with intending to purchase alcohol in the future. Similarly, individuals who previously abstained from the consumption of alcohol, both the exposure to influencer marketing and the consumption of non-alcoholic beer were associated with intending to consume alcohol. In conclusion, when adolescents were exposed to influencer marketing of non-alcoholic beer they were more likely to consume it, which resulted in an increased likelihood that they would then purchase and consume alcohol.

Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

APE1 shRNA-loaded cancer stem cell-derived extracellular vesicles reverse Erlotinib resistance in non-small cell lung cancer via the IL-6/STAT3 signalling.

OBJECTIVE: Apurinic endonuclease 1 (APE1) has been suggested as an oncogene of lung tumours and our bioinformatics analysis identified the association between Erlotinib resistance and interleukin-6 (IL-6). Thus, we performed this work to delineate the mechanistic actions of APE1/IL-6 signalling in Erlotinib resistance of non-small cell lung cancer (NSCLC). METHODS: We selected human NSCLC cell lines HCC827 and PC9 to establish Erlotinib-resistant HCC827R and PC9R cells. Cancer stem cells (CSCs) were isolated from Erlotinib-sensitive HCC827P and PC9P cells (PCSCs) and from HCC827R and PC9R cells (RCSCs). Further, extracellular vesicles (EVs) were separated from PCSCs (PCSC-EVs) and RCSCs (RCSC-EVs) and co-cultured with RCSCs with or without short hairpin RNA (shRNA)-targeting APE1 (APE1 shRNA) transduction. In addition, functional assays were conducted to determine the effect of APE1 shRNA on malignant phenotypes of cancer cells in vitro and in vivo and the activation of IL-6/STAT3 signalling. RESULTS: It was found that NSCLC cells could internalize both RCSC-EVs and PCSC-EVs. RCSC-EVs augmented the resistance of NSCLC cells to Erlotinib. The overexpression of APE1 occurred in NSCLC tissues, and IL-6 was enriched in serum samples of patients with NSCLC. APE1 shRNA was demonstrated to restrict the Erlotinib resistance of NSCLC cells by inactivating the IL-6/STAT3 signalling. Additionally, shAPE1-loaded RCSC-EVs suppressed the Erlotinib resistance of NSCLC via the IL-6/STAT3 axis both in vitro and in vivo, as reflected by impeded malignant phenotypes and xenograft tumour formation. CONCLUSIONS: Collectively, these data indicate that APE1 confers Erlotinib resistance by activating the IL-6/STAT3 signalling, suggesting targeting APE1 as a possible therapeutic target in Erlotinib-resistant NSCLC.

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling.

SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR, immunohistochemistry, and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan-Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP-induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with low expression of SOX2, and even including its regulating APE1, survived longer than those with high expression of SOX2, and APE1. siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.

ERCC1 polymorphism and its expression associated with ischemic stroke in Chinese population.

Background: Excision repair cross-complementing group 1 (ERCC1) was considered a potential candidate gene for ischemic stroke, and its polymorphisms might be associated with the susceptibility to ischemic stroke. Methods: A total of 513 patients with ischemic stroke and 550 control subjects were recruited. The expression levels of ERCC1 messenger RNA (mRNA) in peripheral blood mononuclear cells and its protein in plasma were detected by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Rs3212986 polymorphism of ERCC1 was detected by PCR-restriction fragment length polymorphism (RFLP-PCR) and was confirmed by sequencing. The association between the ERCC1 rs3212986 polymorphism or its expression and ischemic stroke was further analyzed. Results: The ERCC1 mRNA level in patients with ischemic stroke was lower than that in the control group (P < 0.05). However, the ERCC1 protein level in patients with ischemic stroke was higher than that in the control group (P < 0.05). The A allele of rs3212986 was associated with increased ischemic stroke risk (OR = 1.287, 95% CI = 1.076-1.540, P = 0.006). The association between rs3212986 polymorphism and ischemic stroke susceptibility was found in both recessive (OR = 2.638, 95% CI = 1.744-3.989, P < 0.001) and additive models (OR = 1.309, 95% CI = 1.028-1.667, P = 0.031), respectively. Similar results were obtained in the recessive model (OR = 2.015, 95% CI = 1.087-3.704, P = 0.026) after adjusting for demographic information and other variables. Additionally, the level of ERCC1 mRNA in the CC/CA genotype was higher than that in the AA genotype (P < 0.05). Conclusion: It was suggested that the ERCC1 rs3212986 polymorphism was associated with ischemic stroke susceptibility in a Chinese Han population and that an A allele of rs3212986 was related to increased ischemic stroke risk. The altered ERCC1 expression level caused by the rs3212986 polymorphism might participate in the pathophysiological process of ischemic stroke.

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway.

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

Targeting DNAJC19 overcomes tumor growth and lung metastasis in NSCLC by regulating PI3K/AKT signaling.

BACKGROUND: Some driver oncogenes are still unknown in non-small-cell lung cancer (NSCLC). DNAJC19, a major component of the translocation machinery of mitochondrial membranes, is a disease-associated protein. Herein, we report the role of DNAJC19 in NSCLC cell growth and metastasis. METHODS: Immunohistochemistry (IHC) was performed to investigate DNAJC19 expression in NSCLC clinical samples. For knockdown or overexpression assays in A549 or NCI-H1299 lung cancer cells, lentiviral vectors were used. After assessment of cell functions, DNAJC19-knockdown A549 cells were further applied to establish mouse xenograft and metastasis tumor models. Assessments based on the RNA-seq data, western blotting, PCR and IHC were performed for the mechanistic study. RESULTS: Expression of DNAJC19 was higher in tumors than in noncancerous adjacent tissues. Survival analysis indicated that low DNAJC19 levels were correlated with an increased progression-free survival rate. ShRNA-mediated knockdown of DNAJC19 markedly inhibited cell growth, viability, migration and invasion. Moreover, RNA-seq analysis revealed that the PI3K/AKT signaling pathway was involved in molecular events when A549 cells were treated with shDNAJC19. In addition, DNAJC19 knockdown decreased PI3Kp85a, AKT and p-AKT expression in A549 cells, and cellular functions were greatly rescued in DNAJC19-knockdown A549 cells by ectopic overexpression of AKT. Furthermore, tumor xenograft growth and lung metastasis were markedly repressed in the shDNAJC19 group compared to the control group. As expected, the expression levels of DNAJC19, PI3K and AKT in xenograft mouse samples were also lower in the shDNAJC19 group than in the shCtrl group. CONCLUSIONS: DNAJC19 greatly promotes NSCLC cell growth and lung metastasis by regulating PI3K/AKT signaling, providing a novel therapeutic target for treating NSCLC patients.

Biomimetic Mineralization of Tannic Acid-Supplemented HEMA/SBMA Nanocomposite Hydrogels.

This study developed a tannic acid (TA)-supplemented 2-hydroxyethyl methacrylate-co-sulfobetaine methacrylate (HEMA-co-SBMA) nanocomposite hydrogel with mineralization and antibacterial functions. Initially, hybrid hydrogels were synthesized by incorporating SBMA into the HEMA network and the influence of SBMA on the chemical structure, water content, mechanical properties, and antibacterial characteristics of the hybrid HEMA/SBMA hydrogels was examined. Then, nanoclay (Laponite XLG) was introduced into the hybrid HEMA/SBMA hydrogels and the effects evaluated of the nanoclay on the chemical structure, water content, and mechanical properties of these supplemented hydrogels. The 50/50 hybrid HEMA/SBMA hydrogel with 30 mg/mL nanoclay showed outstanding mechanical properties (3 MPa) and water content (60%) compared to pure polyHEMA hydrogels. TA then went on to be incorporated into these hybrid nanocomposite hydrogels and its effects investigated on biomimetic mineralization. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) showed that bone-like spheroidal precipitates with a Ca/P ratio of 1.67% were observed after 28 days within these mineralized hydrogels. These mineralized hydrogels demonstrated an almost 1.5-fold increase in compressive moduli compared to the hydrogels without mineralization. These multifunctional hydrogels display good mechanical and biomimetic properties and may have applications in bone regeneration therapies.

Landscape forest impacts the potential activity time of an invasive lizard and its possibilities for range expansion in Taiwan under climate warming.

Climate warming may have an impact on invasive species and their ecological consequences. Invasive reptiles, which have temperature-dependent physiology, are expected to be greatly impacted by climate warming, though data supporting this is limited. We investigated the potential impact of a warmer climate on an invasive lizard, Eutropis multifasciata, in Taiwan. A mechanistic model, NicheMapR, was used to simulate the maximum activity time available at three elevations, with varying forest densities, under the current climate and a warmer scenario. The results show that climate warming will provide this species more time for activity in the currently occupied lowland region but not in the mountain areas, which are covered with dense forests. However, if the landscape becomes more open in mountain areas, it will become more suitable for this species and may enable an expansion upslope. Our results show that climate warming has a positive impact on this species, and that landscape's characteristics profoundly modulate its impact and the possibilities for elevational expansion in the future.

LigaSure small jaw versus conventional neck dissection: a systematic review and meta-analysis.

BACKGROUND: Neck dissection has a central role in the management of head and neck cancers. This systematic review aimed to compare the intraoperative and postoperative parameters between conventional and LigaSure Small Jaw (LSJ)-assisted neck dissection. METHODS: PubMed (MEDLINE), Embase, and the Cochrane Library were searched. independently by two authors for relevant articles comparing the outcomes of conventional and LSJ-assisted neck dissection. Data from each study were extracted, and a random-effects model was used in the pooled analysis. RESULTS: Compared with conventional techniques, LSJ-assisted neck dissection was associated with a significantly reduced operative time. The rates of postoperative hematoma, infection, amount of intraoperative blood loss, the length of hospital stay and the drainage amount showed no significant intergroup differences. CONCLUSIONS: The meta-analysis provides evidence that properly using LSJ may reduce the operative time compared with that of conventional techniques. Surgeons may consider using LSJ in neck dissection according to personal experiences.

Complete mitochondrial genome of the Ruff, Calidris pugnax (Aves, Scolopacidae).

This paper reports the mitochondrial genome of Calidris pugnax, which is a closed circular molecule of 16,902 bp. The overall base composition of this species is 25.2% T, 30.6% C, 32.0% A, and 12.2% G, with an A + T content of 55.2%. The structure of the mitogenome is a typical vertebrate mitochondrial gene arrangement. Phylogenetic analysis of complete mitochondrial genome concatenated sequences from 13 species from 6 genera was conducted using the maximum-likelihood (ML) model. The topology demonstrated that the mitogenome of this species was genetically closest to that of Calidris tenuirostris. Calidris pugnax mitogenome can contribute to our understanding of the phylogeny and evolution of this species.

NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-Associated gastric cancer.

Helicobacter pylori infection is an important pathogenic risk factor for gastric cancer, but it is still unclear what tumor markers for gastric cancer induced by H. pylori can be consistently detected. Using an miRNA microarray, we found that miR-18a-3p (6.02-fold) and miR-4286 (5.73-fold) were significantly increased in H. pylori- associated gastric cancer. In a cohort of gastric cancer patients (N = 104), serum expression of miR-18a-3p and miR-4286 was positively and significantly correlated with H. pylori; furthermore, miR-18a-3p was positively correlated with invasion (P = 0.029), and miR-4286 was positively correlated with tumor stage (P = 0.033), tumor size (P = 0.041), and lymph node metastasis (P = 0.009). Overexpression of miR-18a-3p and miR-4286 also increased cancer cell proliferation and motility and both inhibited expression of BZRAP1, resulting in tumor progression in vitro. In addition, lipopolysaccharide co-mediated the expression of miR-18a-3p and miR-4286 by activating the NF-κB transcription factor, but TAK-242 (TLR4 inhibitor) blocked this effect. These results demonstrate that serum miR-18a-3p and miR-4286 levels in H. pylori-associated gastric cancer may be useful prognostic biomarkers and suggest a novel signaling pathway of targeting BZRAP1 in gastric cancer.

Superhydrophilic Coating with Antibacterial and Oil-Repellent Properties via NaIO4-Triggered Polydopamine/Sulfobetaine Methacrylate Polymerization.

Superhydrophilic coatings have been widely used for the surface modification of membranes or biomedical devices owing to their excellent antifouling properties. However, simplifying the modification processes of such materials remains challenging. In this study, we developed a simple and rapid one-step co-deposition process using an oxidant trigger to fabricate superhydrophilic surfaces based on dopamine chemistry with sulfobetaine methacrylate (SBMA). We studied the effect of different oxidants and SBMA concentrations on surface modification in detail using UV-VIS spectrophotometry, dynamic light scattering, atomic force microscopy, X-ray photoelectron spectroscopy, and surface plasmon resonance. We found that NaIO4 could trigger the rate of polymerization and the optimum ratio of dopamine to SBMA is 1:25 by weight. This makes the surface superhydrophilic (water contact angle < 10°) and antifouling. The superhydrophilic coating, when introduced to polyester membranes, showed great potential for oil/water separation. Our study provides a complete description of the simple and fast preparation of superhydrophilic coatings for surface modification based on mussel-inspired chemistry.

Low cold tolerance of the invasive lizard Eutropis multifasciata constrains its potential elevation distribution in Taiwan.

1. The invasive many-lined sun skink, Eutropis multifasciata, is established in much of southern Taiwan and is spreading northward. We investigated whether winter temperatures constrain further dispersion of this skink by comparing its cold tolerance to the spatial distribution of winter temperatures in Taiwan. 2. We measured the 28-day survival rate of this species at 4 constant temperatures (10-16 °C in 2 °C increments) and its critical thermal minimum (CTmin), i.e., the body temperature at which the righting reflex is lost during the cooling process. For comparison with the spatial distribution of temperatures over Taiwan, we used the biophysical model Niche Mapper™ in order to simulate the soil temperatures, where lizards are inactive in the winter, during the coldest month of the year, January, under three climatic scenarios (average temperature, average-3 °C, average+3 °C). 3. Our results indicate that this species has low tolerance to cold. Combining cold tolerance data with soil temperature data suggests that its upper elevation limit could range from 1000 m to 1500 m, above which the weather is lethal and precludes overwintering. The locations of sightings of E. multifasciata are consistent with this prediction, with no known locations above 500 m elevation. 4. This study highlights that the winter climate is a major factor in determining population establishment and hence in limiting this species' range. Future studies would benefit from accounting for low winter temperatures and their potential influence on range limits of invasive species.

The complete mitochondrial genome of Asian brown flycatcher Muscicapa latirostris (Passeriformes: Muscicapidae).

We report the mitochondrial genome of Muscicapa latirostris. The overall base composition of the Asian brown flycatcher mitogenome is 24.31% T, 31.62% C, 29.62% A, and 14.44% G, with an A + T content of 53.93%. The total length of the sequence is 18,026 bp (13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 control regions). Phylogenetic analysis was performed based on the concatenated nucleotide sequences of cytochrome c oxidase subunit I and cytochrome b using the neighbor-joining method and the Kimura 2-parameter model in MEGA 7.0 with 1000 bootstrap replicates.

Painless skin electroporation as a novel way for insulin delivery.

BACKGROUND: Rigorous research efforts have been undertaken worldwide to develop a needle-free insulin delivery for many decades with limited success. This translational study aims to deliver insulin through skin with painless electroporation. METHODS: A recently designed microelectrode array was used to deliver insulin in mice with diabetes under electroporation conditions that are painless and harmless on human skin. RESULTS: Under such condition, a therapeutic amount of insulin was delivered successfully through mouse skin. Electroporation alone increased insulin transport around 100-fold compared with passive diffusion. Increased skin temperature to 40°C for 20 min augmented insulin transport to 237-fold more than the control value. Repeated electroporation showed no harm on human skin. CONCLUSION: The results indicate the potential of painless delivery of insulin through human skin in future clinical practice.