TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. METHODS: The clinical significance of Tripartite Motif Containing 29 (TRIM29) was identified by exploring GEO datasets and TCGA database and its potential biological functions were predicted by GSEA analysis. The regulatory axis was established by bioinformatics analysis and validated by mechanical experiments. Then, in vitro and in vivo assays were performed to validate the roles of TRIM29 in PDAC GEM resistance. RESULTS: High TRIM29 expression was associated with poor prognosis of PDAC and functional experiments demonstrated that TRIM29 promoted GEM resistance in PDAC GEM-resistant (GR) cells. Furthermore, we revealed that circRPS29 promoted TRIM29 expression via competitive interaction with miR-770-5p and then activated MEK/ERK signaling pathway. Additionally, both in vitro and in vivo functional experiments demonstrated that circRPS29/miR-770-5p/TRIM29 axis promoted PDAC GEM resistance via activating MEK/ERK signaling pathway. CONCLUSION: Our results identify the significance of the signaling axis, circRPS29/miR-770-5p/TRIM29-MEK/ERK, in PDAC GEM resistance, which will provide novel therapeutic targets for PDAC treatment.

Case report: A case of epidermolysis bullosa complicated with pyloric atresia and a literature review.

Objective: This article aims to explore the diagnosis, molecular characteristics, treatment, and prognosis of epidermolysis bullosa with pyloric atresia (EB-PA). Methods: The clinical manifestations, diagnosis and treatment, and genetic characteristics of a patient with EB-PA admitted to our hospital were analysed. The disease subtypes, concomitant abnormalities, molecular characteristics, and prognosis of patients with EB-PA were summarized by searching the EB-PA-related literature since 2011. Results: We present a very low birth weight female infant with skin blisters and pyloric obstruction. Exome sequencing revealed heterozygous mutations in the ITGB4 gene: c.794dupC (p. S265fs*5) and c.2962G > A (p.A988T). This infant was diagnosed with EB-PA. Coverage of the wounds and Penicillin were used to prevent infection, but the patient eventually developed severe sepsis. A literature review was carried out including 49 cases of EB-PA; among these cases, 34 were preterm infants, weighing between 930 and 3,640 g. Of these EB-PA patients, 28 had accompanying malformations, including urinary system malformations and aplasia cutis congenita (ACC). Thirty-two patients identified the subtype of EB-PA, of whom 25 were diagnosed with junctional epidermolysis bullosa (JEB), 6 with epidermolysis bullosa simplex (EBS), and 1 with dystrophic epidermolysis bullosa (DEB). Genetic testing was conducted on 23 patients, of whom 15 carried Integrin Beta-4 (ITGB4) gene mutations and one JEB patient carried an Integrin Alpha-6 (ITGA6) gene mutation; 4 of the 5 EBS patients had Plectin (PLEC) gene mutations, and the other had an ITGB4 mutation. ITGB4 mutation cases involved 29 mutation sites, primarily concentrated in the region encoding the integrin beta subunit; PLEC mutation cases involved 7 mutation sites. Among all cases, 43 underwent pyloric atresia surgery, of whom 24 died postoperatively, and 6 without surgery therapy died within a short period. Conclusion: EB-PA is a rare genetic disorder characterized by increased skin fragility and PA involving mutations in the ITGB4, PLEC, or ITGA6 genes. EB-PA has a high incidence of complications and mortality, surgery and supportive therapy are currently the most common treatment options.

The m6A methyltransferase METTL3 affects cell proliferation and migration by regulating YAP expression in Hirschsprung disease.

BACKGROUND: METTL3, an mRNA m6A methyltransferase, has been implicated in various steps of mRNA metabolism, such as stabilization, splicing, nuclear transportation, translation, and degradation. However, whether METTL3 dysregulation is involved in Hirschsprung disease (HSCR) development remains unclear. In this study, we preliminarily elucidated the role of METTL3 in HSCR and sought to identify the associated molecular mechanism. METHODS: The gene expression levels of YAP and several methyltransferases, demethylases, and effectors were evaluated by RT-qPCR. Protein levels were evaluated by western blot and immunohistochemistry. Cell proliferation and migration were detected by CCK-8 and Transwell assays, respectively. The overall levels of m6A modification were determined by colorimetry. RESULTS: We found that m6A levels were reduced in the stenotic intestinal tissue of patients with HSCR. When METTL3 was knocked down in SH-SY5Y and HEK-293T cells, the proliferative and migratory abilities of the cells were inhibited, m6A modification levels were reduced, and YAP expression was increased. Importantly, YAP and METTL3 expression displayed a negative correlation in both cell lines as well as in HSCR tissue. CONCLUSIONS: Our results provide evidence for an interaction between METTL3 and YAP in HSCR, and further suggest that METTL3 is involved in the pathogenesis of HSCR by regulating neural crest cell proliferation and migration upstream of YAP.

Association of rs2435357 and rs2506030 polymorphisms in RET with susceptibility to hirschsprung disease: A systematic review and meta-analysis.

Background: There are numerous published studies on the association between RET polymorphisms and susceptibility to Hirschsprung disease (HSCR). However, some of the results are inconsistent and the studies were conducted with small sample sizes. Therefore, we performed a meta-analysis to clarify the relationship. Methods: Relevant data were retrieved from PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, and Google Scholar according to PRISMA guidelines. Odds ratios (OR) were calculated to assess susceptibility to HSCR. Meanwhile, heterogeneity and publication bias were also calculated by R software package (version 4.2.1). The protocol was published in PROSPERO (CRD42022348940). Results: A total of 12 studies were included in the meta-analysis and comprised 12 studies on the RET polymorphism rs2435357 (1,939 subjects and 3,613 controls) and 7 studies on the RET polymorphism rs2506030 (1,849 patients with HSCR and 3,054 controls). The analysis revealed that rs2435357 [A vs. G: odds ratio (OR) = 3.842, 95% confidence interval (CI) 2.829-5.220; AA vs. GG: OR = 2.597, 95% CI 1.499-4.501; AA + AG vs. GG: OR = 6.789, 95% CI 3.0711-14.9973; AA vs. AG + GG: OR = 8.156, 95%CI 5.429-12.253] and rs2506030 (A vs. G: OR = 0.519, 95% CI 0.469-0.573; AA vs. GG: OR = 0.543, 95% CI 0.474-0.623; AA + AG vs. GG: OR = 0.410, 95% CI 0.360-0.468; AA vs. AG + GG: OR = 0.361, 95%CI 0.292-0.447) were significantly associated with susceptibility to HSCR. Conclusions: The polymorphisms rs2435357 and rs2506030 in the RET may be related to susceptibility to HSCR, of which rs2435357 (T > C) is the causal locus and rs2506030 (A > G) is the protective locus. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier:CRD42022348940.

UV Treatment of Flexible Copper Nanowire Mesh Films for Transparent Conductor Applications.

Copper nanowires have the potential to reach and even exceed the indium tin oxide performances as flexible transparent conductive electrodes. However, for a large-scale production, they need to be fabricated in a high-speed, low-cost way, without degrading the flexible substrate. One of the major bottlenecks resides in the post-treatment used to remove organic residues from the surface of the nanowires after forming the transparent electrode, which is necessary to obtain high optoelectronic performances. Here, we propose an ultra-violet irradiation and a subsequent acetic acid bath as an easy, scalable, fast post-treatment. After only 2 min of ultra-violet treatment, followed by 10 min of acid bath, an Rs of 42 Ω sq-1 and a T 550 nm of 87% were measured. Besides, copper nanowire electrodes maintained their high transparency in the range 750-2500 nm, which makes them good candidates for applications such as infrared solar cells.

Comparative measurements of piezoelectric coefficient of PZT films by Berlincourt, interferometer, and vibrometer methods.

Chemical solution deposition (CSD) techniques were used to prepare lead zirconate (Zr) titanate (Ti) (PZT) thin films with Zr/Ti ratios of 30/70 and 52/48. Usually CSD processing is restricted to making crack-free, single-layer films of 70-nm thick, but modifications to the sol-gel process have permitted the fabrication of dense, crack-free, single layers up to 200 to 300 nm thick, which can be built-up into layers up to 3-microm thick. Thicker PZT films (> 2-microm single layer) can be produced by using a composite sol-gel/ceramic process. Knowledge of the electroactive properties of these materials is essential for modeling and design of novel micro-electromechanical systems (MEMS) devices, but accurate measurement of these properties is by no means straightforward. A novel, double-beam, common-path laser interferometer has been developed to measure the longitudinal (d33) piezoelectric coefficient in films; the results were compared with the values obtained by Berlin-court and laser scanning vibrometer methods. It was found that, for thin-film samples, the d(33,f) values obtained from the Berlincourt method are usually larger: than those obtained from the interferometer and the vibrometer methods; the reasons for this are discussed.

Fabrication and modeling of high-frequency PZT composite thick film membrane resonators.

High-frequency, thickness mode resonators were fabricated using a 7 microm piezoelectric transducer (PZT) thick film that was produced using a modified composite ceramic sol-gel process. Initial studies dealt with the integration of the PZT thick film onto the substrate. Zirconium oxide (ZrO2) was selected as a diffusion barrier layer and gave good results when used in conjunction with silicon oxide (SiO2) as an etch stop layer. Using these conditions, devices were produced and the acoustic properties measured and modeled. The resonators showed a resonant frequency of about 200 MHz, an effective electromechanical coupling coefficient of 0.34, and a Q factor of 22. Modeling was based on a Mason-type model that gave good agreement between the experimental data and the simulations. The latter showed, for the PZT thick film, an electromechanical coupling coefficient of 0.35, a stiffness of 8.65 x 10(10) N x m(-2) and an e33,f piezoelectric coefficient of 9 C x m(-2).