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A film with elaborate microstructures that offers biomimetic properties and multi functionalities is highly desired in wound healing. Here, we develop an aligned hydrogel fiber film integrated with multi-active constituents to promote wound healing. Such fiber films are designed and constructed by photo-crosslinking the methacrylate gelatin (GelMA) doped with silver nanoparticles (Ag NPs) and iridium nanoparticles coated with polyvinylpyrrolidone (PVP-Ir NPs) in the precursor solution using electrospinning. The nature of GelMA hydrogel and the aligned arrangement of nanofibers endow the film with high-water content, self-degradability, improved bionic characteristics, oriented cell growth, and improved cell proliferation and migration. Moreover, the encapsulated nanozymes and Ag NPs offer the fiber film with superior reactive oxygen species (ROS) scavenging and antibacterial capability. The infected wound model shows that the multi-active hydrogel fiber film can reduce inflammation by killing bacteria and decomposing ROS, which accelerates the growth of new blood vessels and granulation tissue. Benefitting from these features, the versatile aligned GelMA fiber film demonstrates the clinically translational potential for wound healing.

Background Emerging evidence suggests that competing endogenous RNAs plays a crucial role in the development and progress of pancreatic adenocarcinoma (PAAD). The objective was to identify a new lncRNA-miRNA-mRNA network as prognostic markers, and develop and validate a multi-mRNAs-based classifier for predicting overall survival (OS) in PAAD. Methods Data on pancreatic RNA expression and clinical information of 445 PAAD patients and 328 normal subjects were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Genotype-Tissue Expression (GTEx). The weighted correlation network analysis (WGCNA) was used to analyze long non-coding RNA (lncRNA) and mRNA, clustering genes with similar expression patterns. MiRcode was used to predict the sponge microRNAs (miRNAs) corresponding to lncRNAs. The downstream targeted mRNAs of miRNAs were identified by starBase, miRDB, miRTarBase and Targetscan. A multi-mRNAs-based classifier was develop using least absolute shrinkage and selection operator method (LASSO) COX regression model, which was tested in an independent validation cohort. Results A lncRNA-miRNA-mRNA co-expression network which consisted of 60 lncRNAs, 3 miRNAs and 3 mRNAs associated with the prognosis of patients with PAAD was established. In addition, we constructed a 14-mRNAs-based classifier based on a training cohort composed of 178 PAAD patients, of which the area under receiver operating characteristic (AUC) in predicting 1-year, 3-year, and 5-year OS was 0.719, 0.806 and 0.794, respectively. The classifier also shown good prediction function in independent verification cohorts, with the AUC of 0.604, 0.639 and 0.607, respectively. Conclusions A novel competitive endogenous RNA (ceRNA) network associated with progression of PAAD could be used as a reference for future molecular biology research.

Background Long noncoding ribonucleic acid (lncRNA) promoter methylation is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Thus, we aim to screen and verify the lncRNA promoter methylation sites associated with overall survival (OS), vascular invasion, pathological grade, and clinical stage in HCC. Methods Methylation-related data including clinical characteristic, transcriptome, methylation, and messenger RNA (mRNA) expression were taken from the Cancer Genome Atlas (TCGA) database. The OS, vascular invasion, pathological grade, and clinical stage-related lncRNA promoter methylation models were developed by the least absolute shrinkage and selection operator (LASSO) algorithm based on the lncRNA promoter methylation sites screened via R software. The Kaplan–Meier analysis, the area under the receiver operating characteristic (ROC) curve (AUC), the calibration curve (C-index) were performed to evaluate the performance of these models. Finally, the methylation-specific polymerase chain reaction (MS-PCR) was performed to verify the accuracy of these models based on 146 HCC tissues from our hospital. Results A total of 10 methylation sites were included in the OS-related lncRNA promoter methylation model that could effectively divide HCC patients into high-risk and low-risk groups (P < 0.0001) via survival analysis. COX univariable and multivariable regression analysis found that the OS-related model (P < 0.001, 95% CI 1.378–2.942) and T stage (P < 0.001, 95% CI 1.490–3.418) were independent risk factors affecting OS in HCC patients. The vascular invasion-related model contained 8 methylation sites with its AUC value of 0.657; the pathological grade-related model contained 22 methylation sites with its AUC value of 0.797; the clinical stage-related model contained 13 methylation sites with its AUC of 0.724. Target genes corresponded to vascular invasion-related lncRNA promoter methylation sites were involved in many kinds of biological processes in HCC such as PI3K-Akt signaling pathway. The accuracy of the vascular invasion-related model was consistent with our bioinformatics conclusion after being verified via MS-PCR. Conclusion The lncRNA promoter methylation sites are closely correlated with the process of HCC and can be utilized to improve the therapy and prognosis of HCC.

An amendment to this paper has been published and can be accessed via the original article.

Pachydermoperiostosis (PDP) is a rare inherited multisystem disease characterized with digital clubbing, pachydermia and periostosis. Variants in either HPGD or SLCO2A1 that interrupt the prostaglandin E2 (PGE 2 ) pathway have been shown to be involved in PDP. Here, in addition to six confirmed variants in HPGD or SLCO2A1 , we identified four novel SLCO2A1 variants in eight PDP patients from seven Chinese Han families. In addition, gastric mucosa hyperplasia was observed in all affected individuals and interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα) and receptor activator of nuclear factor kappa ligand (RANKL) expression were elevated in hypertrophic gastric mucosa. Two of eight patients who had severe arthralgia were treated with celecoxib. After three months, their arthralgia was partly relieved and IL-6, TNFα and RANKL expression were decreased in accordance with their relieved hypertrophic gastric mucosa. Our study broadens the variation spectrum of SLCO2A1 and suggests that the gastric mucosa hyperplasia might be a common characteristic of PDP. Moreover, celecoxib would be a considerable choice for PDP patients. We also revealed that IL-6, TNFα and RANKL may play important roles in the molecular mechanisms of gastric mucosa hyperplasia in PDP for the first time.

Because of a lack of available miniaturized multiaxial load sensors to measure the normal load and the lateral load simultaneously, quantitative in situ scratch devices inside scanning electron microscopes and the transmission electron microscopes have barely been developed up to now. A novel two-axis load sensor was designed in this paper. With an I-shaped structure, the sensor has the function of measuring the lateral load and the normal load simultaneously, and at the same time it has compact dimensions. Finite element simulations were carried out to evaluate stiffness and modal characteristics. A decoupling algorithm was proposed to resolve the cross-coupling between the two-axis loads. Natural frequency of the sensor was tested. Linearity and decoupling parameters were obtained from the calibration experiments, which indicate that the sensor has good linearity and the cross-coupling between the two axes is not strong. Via the decoupling algorithm and the corresponding decoupling parameters, simultaneous measurement of the lateral load and the normal load can be realized via the developed two-axis load sensor. Preliminary applications of the load sensor for scratch testing indicate that the load sensor can work well during the scratch testing. Taking advantage of the compact structure, it has the potential ability for applications in quantitative in situ scratch testing inside SEMs.

BackgroundChronic enteropathy associated with the SLCO2A1 gene (CEAS) is an enteropathy characterized by multiple small intestinal ulcers of nonspecific histology, also known as chronic nonspecific multiple ulcers of the small intestine. The SLCO2A1 gene encodes a prostaglandin transporter (PGT).AimsThe aim of this study was to investigate the clinical characteristics of ten Chinese patients with intestinal ulcers of unknown origin, screen them for variants of SLCO2A1, and to investigate the expression of PGT in the small intestinal mucosa of patients with CEAS.MethodsTen Chinese patients with intestinal ulcers of unknown origin were included in this study. Blood samples were collected for whole-exome sequencing and Sanger sequencing of candidate gene variants. Immunohistochemical staining was used to investigate the expression of PGT.ResultsThese ten patients were clinically diagnosed with intestinal ulcers of unknown origin based on criteria established according to earlier publications. Three of them were genetically diagnosed as having CEAS and four candidate variants of the SLCO2A1 gene were identified, among which c.941-1G>A, c.178G>A and c.1681C>T were detected in patients with CEAS for the first time. The terminal ileum was involved in all three patients with CEAS in our study, which was different from the results of Japanese patients. The expression of PGT in the vascular endothelial cells of the intestinal mucosa tissues of patients with CEAS was negative or intermediate.ConclusionWe summarized the clinical data of ten Chinese patients with intestinal ulcers of unknown origin and identified three novel SLCO2A1 variants from three patients with CEAS. This study improves our understanding of CEAS and broadens the spectrum of SLCO2A1 variants known to cause CEAS.

Background Peutz‐Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development. Objective This study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps. Methods Polyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes. Results Our findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid‐derived suppressor cells (MDSCs). Conclusion The findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.

Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast cancer by inhibiting CHEK2’s activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast cancer, which protects cells from apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast cancer.

Repacking enhances crystal mush permeability, accelerating melt extraction. However, identifying microstructural records of repacking is challenging, creating a gap in quantifying its effect on magmatic reservoirs. We identified extracted melt (rhyolite) and silicic residue (quartz monzonite) through textures and geochemical characteristics in the Pangduo Basin (Southern Tibet; ∼50 Ma old). By calculating interstitial mineral proportions and modeling incompatible element concentrations in quartz monzonite, we estimate a moderate trapped melt fraction (∼50 vol. %), providing microtextural evidence of repacking at intermediate crystallinities. We interpret that the horizontal preferred orientation of frame‐forming feldspars produces micro‐scale melt channels that accelerate melt extraction. Modeling the intensity of this orientation, we estimated compressive strain to be 20%–30%, likely accelerating melt extraction by at least 15 times. This millennium timescale allows for the growth of a large magma chamber, preventing the melt from freezing or causing multiple small eruptions due to excessive flow‐induced stress. Plain Language Summary Explosive rhyolite eruptions significantly affect climate, the environment, and human life. These devastating events, involving crystal‐melt separation in large upper crustal magma reservoirs, may be accelerated by grain reorganization. Yet, quantifying this acceleration is complex. Our study utilizes samples from the Pangduo Basin in southern Tibet to examine the pertinent microstructure and calculate the acceleration rate of crystal‐melt separation. We found that grain reorganization can reduce the separation duration by a factor of 15, highlighting its critical role in crystal‐melt separation. Key Points The rhyolite and quartz monzonite of the Pangduo Basin represent extracted melt and corresponding residual cumulates, respectively Interstitial minerals fraction and mass‐balance calculations yield a moderate trapped melt fraction of ∼50 vol. % The horizontal preferred orientation of large‐grained feldspars accelerates melt extraction by at least 15 times