PRNP is a pan-cancer prognostic and immunity-related to EMT in colorectal cancer.

Background: Prion protein gene (PRNP) is widely expressed in a variety of tissues. Although the roles of PRNP in several cancers have been investigated, no pan-cancer analysis has revealed its relationship with tumorigenesis and immunity. Methods: Comprehensive analyses were conducted on The Cancer Genome Atlas (TCGA) Pan-Cancer dataset from the University of California Santa Cruz (UCSC) database to determine the expression of PRNP and its potential prognostic implications. Immune infiltration and enrichment analysis methods were used to ascertain correlations between PRNP expression levels, tumor immunity, and immunotherapy. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods were employed to examine possible signaling pathways involving PRNP. In vitro experiments using CCK-8 assay, Wound healing assay, and Transwell assay to detect the effect of Cellular prion protein (PrPC) on proliferation, migration, and invasion in colorectal cancer (CRC) cells. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin, E-cadherin, Vimentin and Snail) were detected by western blot. Results: Among most cancer types, PRNP is expressed at high levels, which is linked to the prognosis of patients. PRNP expression is strongly associated with immune infiltrating cells, immunosuppressive cell infiltration and immune checkpoint molecules. In addition to tumor mutation burden (TMB), substantial correlations are detected between PRNP expression and microsatellite instability (MSI) in several cancers. In vitro cell studies inferred that PrPC enhanced the proliferation, migration, invasion, and EMT of CRC cells. Conclusion: PRNP serves as an immune-related prognostic marker that holds promise for predicting outcomes related to CRC immunotherapy while simultaneously promoting cell proliferation, migration, and invasion activities. Furthermore, it potentially plays a role in governing EMT regulation within CRC.

Formation of Stable Vascular Networks by 3D Coaxial Printing and Schiff-Based Reaction.

Vascularized organs hold potential for various applications, such as organ transplantation, drug screening, and pathological model establishment. Nevertheless, the in vitro construction of such organs encounters many challenges, including the incorporation of intricate vascular networks, the regulation of blood vessel connectivity, and the degree of endothelialization within the inner cavities. Natural polymeric hydrogels, such as gelatin and alginate, have been widely used in three-dimensional (3D) bioprinting since 2005. However, a significant disparity exists between the mechanical properties of the hydrogel materials and those of human soft tissues, necessitating the enhancement of their mechanical properties through modifications or crosslinking. In this study, we aim to enhance the structural stability of gelatin-alginate hydrogels by crosslinking gelatin molecules with oxidized pullulan (i.e., a polysaccharide) and alginate molecules with calcium chloride (CaCl2). A continuous small-diameter vascular network with an average outer diameter of 1 mm and an endothelialized inner surface is constructed by printing the cell-laden hydrogels as bioinks using a coaxial 3D bioprinter. The findings demonstrate that the single oxidized pullulan crosslinked gelatin and oxidized pullulan/CaCl2 double-crosslinked gelatin-alginate hydrogels both exhibit a superior structural stability compared to their origins and CaCl2 solely crosslinked gelatin-alginate hydrogels. Moreover, the innovative gelatin and gelatin-alginate hydrogels, which have excellent biocompatibilities and very low prices compared with other hydrogels, can be used directly for tissue/organ construction, tissue/organ repairment, and cell/drug transportation.

Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair.

Spinal cord injury (SCI) often leads to a severe permanent disability. A poor inflammatory microenvironment and nerve electric signal conduction block are the main reasons for difficulty in spinal cord nerve regeneration. In this study, black phosphorus (BP) and glycyrrhizic acid (GA) are integrated into methacrylate-modified silk fibroin (SF) to construct a bifunctional injectable hydrogel (SF/BP/GA) with appropriate conductivity and the ability to inhibit inflammation to promote neuronal regeneration after SCI. This work discovers that the SF/BP/GA hydrogel can reduce the oxidative damage mediated by oxygen free radicals, promote the polarization of macrophages toward the anti-inflammatory M2 phenotype, reduce the expression of inflammatory factors, and improve the inflammatory microenvironment. Moreover, it induces neural stem cell (NSC) differentiation and neurosphere formation, restores signal conduction at the SCI site in vivo, and ameliorates motor function in mice with spinal cord hemisection, revealing a significant neural repair effect. An injectable, electroconductive, free-radical-scavenging hydrogel is a promising therapeutic strategy for SCI repair.

CC chemokine receptors are prognostic indicators of gastric cancer and are associated with immune infiltration.

BACKGROUND: CC chemokine receptors are responsible for regulating the tumor microenvironment (TME) and participating in carcinogenesis and tumor advancement. However, no functional study has investigated CC chemokine receptors in gastric cancer (GC) prognosis, risk, immunotherapy, or other treatments. METHODS: We conducted a bioinformatics analysis on GC data using online databases, including the Human Protein Atlas (HPA), Kaplan-Meier (KM) plotter, GeneMANIA, MethSurv, the University of ALabama at Birmingham CANcer (UALCAN) Data Analysis Portal, Gene Set Cancer Analysis (GSCA), cBioportal, and Tumor IMmune Estimation Resource (TIMER). RESULTS: We noted that CC chemokine receptor expression correlated with survival in GC. CC chemokine receptor expression was also strongly linked to different tumor-infiltrating immune cells. Additionally, CC chemokine receptors were found to be broadly drug-resistant in GC. CONCLUSION: Our study identifed CC chemokine receptor expression helped in predicting the prognosis of patients diagnosed with GC. The expression level of the CC chemokine receptors was also positively related to multiple tumor-infiltrating lymphocytes (TILs). These findings provide evidence to monitor patients with GC using CC chemokine receptors, which can be used as an effective biomarker for predicting the disease prognosis and be regarded as a therapeutic target for modulating the tumor immune microenvironment.

Bioprinting Technologies and Bioinks for Vascular Model Establishment.

Clinically, large diameter artery defects (diameter larger than 6 mm) can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene. There are many problems in the construction of small diameter blood vessels (diameter between 1 and 3 mm) and microvessels (diameter less than 1 mm), especially in the establishment of complex vascular models with multi-scale branched networks. Throughout history, the vascularization strategies have been divided into three major groups, including self-generated capillaries from implantation, pre-constructed vascular channels, and three-dimensional (3D) printed cell-laden hydrogels. The first group is based on the spontaneous angiogenesis behaviour of cells in the host tissues, which also lays the foundation of capillary angiogenesis in tissue engineering scaffolds. The second group is to vascularize the polymeric vessels (or scaffolds) with endothelial cells. It is hoped that the pre-constructed vessels can be connected with the vascular networks of host tissues with rapid blood perfusion. With the development of bioprinting technologies, various fabrication methods have been achieved to build hierarchical vascular networks with high-precision 3D control. In this review, the latest advances in 3D bioprinting of vascularized tissues/organs are discussed, including new printing techniques and researches on bioinks for promoting angiogenesis, especially coaxial printing, freeform reversible embedded in suspended hydrogel printing, and acoustic assisted printing technologies, and freeform reversible embedded in suspended hydrogel (flash) technology.

Construction and Evaluation of Small-Diameter Bioartificial Arteries Based on a Combined-Mold Technology.

Arterial stenosis or blockage is the leading cause of cardiovascular disease, and the common solution is to substitute the arteries by autologous veins or bypass the blood vessels physically. With the development of science and technology, arteries with diameter larger than 6 mm can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene, clinically. Nevertheless, the construction of a small-diameter (less than 6 mm) artery with living cells has always been a thorny problem. In this study, a suit of combined mold was designed and forged for constructing small-diameter arterial vessels. Based on this combined mold, bioactive arterial vessels containing adipose-derived stem cells (ASCs) and different growth factors (GFs) were assembled together to mimic the inner and middle layers of the natural arteries. Before assembling, ASCs and GFs were loaded into a gelatin/alginate hydrogel. To enhance the mechanical property of the bilayer arterial vessels, polylactic-glycolic acid (PLGA) was applied on the surface of the bilayer vessels to form the outer third layer. The biocompatibility, morphology and mechanical property of the constructed triple-layer arterial vessels were characterized. The morphological results manifested that cells grow well in the gelatin/alginate hydrogels, and ASCs were differentiated into endothelial cells (ECs) and smooth muscle cells (SMCs), respectively. In addition, under the action of shear stress produced by the flow of the culture medium, cells in the hydrogels with high density were connected to each other, similar to the natural vascular endothelial tissues (i.e., endothelia). Especially, the mechanical property of the triple-layer arterial vessels can well meet the anti-stress requirements as human blood vessels. In a word, a small-diameter arterial vessel was successfully constructed through the combined mold and has a promising application prospect as a clinical small-diameter vessel graft.

Gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor in adults: a case report and literature review.

Intussusception mostly occurs in childhood and is rare in adults. Although intussusception can occur in any part of the gastrointestinal tract, gastroduodenal intussusception caused by a gastric tumor is relatively uncommon in clinical practice. A PubMed search identified 24 published cases of gastroduodenal intussusception caused by gastric gastrointestinal stromal tumor (GIST); however, it is possible that we missed other cases not included in PubMed. Here we report a case of gastroduodenal intussusception caused by gastric GIST in an 85-year-old man. He came to the hospital because of recurrent black stools. Plain computed tomography (CT) scan indicated a mass in the gastric antrum, with slight enhancement in the arterial phase on enhanced CT scan. He was diagnosed with GIST. In addition, images indicated that the mass overlapped into the duodenum, and gastroduodenal intussusception was thus considered. Gastroscopy showed a huge mass in the gastric body. According to the gastroscopy and CT results, gastroduodenal intussusception caused by a gastric tumor was considered. The patient underwent complete surgical removal, which revealed a mass originating from the gastric antrum and overlapping into the duodenum. The postoperative pathological diagnosis was intermediate-risk gastric GIST. The patient was followed up for 4 months without tumor recurrence.

Mechanism of stable power generation and nitrogen removal in the ANAMMOX-MFC treating low C/N wastewater.

This study investigated the mechanism of enhanced power generation and nitrogen removal in an ANAMMOX-MFC reactor through subsequent acetate addition. Data showed that nearly 99% total nitrogen removal (≤1 mg L-1) and 1.41 W m-3 power generation were achieved synchronously under low COD/N (∼1.5) after the subsequent addition of acetate (100 mgCOD·L-1). The columbic efficiency of the system has increased by 15 times (from 0.64% to 9.48%) after adding acetate. Batch tests showed that the denitrification and ANAMMOX progress occurred synchronously before acetate addition the nitrogen removal rate was accelerated. A distinct shift of bacterial community driven by acetate addition was discovered. The high throughput sequencing analysis indicated acetate addition stimulated the enrichment of denitrifiers, such as Aquimonas, Bradyrhizobium, Thauera, and the potential exoelectrogens changing from Comamonas to Pseudomonas. Functional genes forecasts based on KEGG database and COG database showed that the expressions of TCA functional genes were highly promoted in ANAMMOX-MFC, which demonstrated the enhanced electron transfer pathway driven by acetate addition under low COD/N ratio.

The Effect of Agarose on 3D Bioprinting.

In three-dimensional (3D) bioprinting, the accuracy, stability, and mechanical properties of the formed structure are very important to the overall composition and internal structure of the complex organ. In traditional 3D bioprinting, low-temperature gelatinization of gelatin is often used to construct complex tissues and organs. However, the hydrosol relies too much on the concentration of gelatin and has limited formation accuracy and stability. In this study, we take advantage of the physical crosslinking of agarose at 35-40 °C to replace the single pregelatinization effect of gelatin in 3D bioprinting, and printing composite gelatin/alginate/agarose hydrogels at two temperatures, i.e., 10 °C and 24 °C, respectively. After in-depth research, we find that the structures manufactured by the pregelatinization method of agarose are significantly more accurate, more stable, and harder than those pregelatined by gelatin. We believe that this research holds the potential to be widely used in the future organ manufacturing fields with high structural accuracy and stability.

Colonic mucinous adenocarcinoma causing intussusception and distant metastasis: A case report.

RATIONALE: Cases of intussusception caused by mucinous carcinoma have been rarely reported, and those caused by colonic mucinous adenocarcinoma (MAC) with distant metastasis were even fewer. PATIENT CONCERNS: A 60-year-old woman who complained of severe pain around the navel with nausea and vomiting for a week was admitted on November 28, 2017. There were multiple watery stools and abdominal pain was worsened over the prior week. DIAGNOSIS: She was diagnosed by abdominal computed tomography, current medical history, and abdominal signs. Her initial diagnosis was acute abdomen, intussusceptions, and intestinal obstruction. The final diagnosis was MAC, which was based on postoperative pathology. INTERVENTIONS: The patient received emergency laparotomy, followed by 5 courses of chemotherapy with oxaliplatin plus capecitabine, and then 6 courses with 5-fluorouracil + oxaliplatin + calcium leucovorin. OUTCOMES: The patient was in good nutritional condition, and no obvious tumor recurrence or metastasis was found until July 9, 2018. LESSONS: Even though the prognosis of colonic MAC is poor, being able to receive timely surgical treatment, good nutritional status and reasonable postoperative chemotherapy are the key factors to prolonging patient's survival.