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Aim: Achieving drug-targeting delivery and environment-responsive releasing to realize imaging-guided precise tumor therapy. Materials & methods: Graphene oxide (GO) was used as the drug-delivery system to load indocyanine green (ICG) and doxorubicin (DOX) to form a GO/ICG&DOX nanoplatform, in which GO can quench the fluorescence of ICG and DOX. MnO2 and folate acid-functionalized erythrocyte membrane were further coated into the surface of GO/ICG&DOX to obtain an FA-EM@MnO2-GO/ICG&DOX nanoplatform. Results: The FA-EM@MnO2-GO/ICG&DOX nanoplatform has longer blood circulation time, precise targeting delivery to tumor tissues and catalase-like activity. Both in vitro and in vivo results demonstrated that the FA-EM@MnO2-GO/ICG&DOX nanoplatform has better therapeutic efficacy. Conclusion: The authors successfully fabricated a glutathione-responsive FA-EM@MnO2-GO/ICG&DOX nanoplatform, which can achieve drug-targeting delivery and precise drug release.

The tumor EMT is a crucial event in tumor pathogenesis and progression. Previous research has established MBD3’s significant role in pancreatic cancer EMT. However, MBD3’s precise role in colon cancer remains unclear and warrants further investigation. Pan-cancer analysis revealed MBD3’s differential expression in various tumors and its significant association with tumor occurrence, growth, and progression. Moreover, analysis of single-cell sequencing and clinical data for colon cancer revealed MBD3 expression’s negative correlation with clinical indicators such as survival prognosis. Functional enrichment analysis confirmed the association between MBD3 and EMT in colon cancer. Pathological examinations, western blotting, and qRT-PCR in vitro and in vivo validated MBD3’s differential expression in colon cancer. Transwell, CCK-8, clone formation, and in vivo tumorigenesis experiments confirmed MBD3’s impact on migration, invasion, and proliferation. Our findings demonstrate MBD3 as a potential prognostic marker and therapeutic target for colon cancer.

As a refractory tumor, pancreatic carcinoma is more vulnerable to ferroptosis, a novel regulated cell death mode. However, the exact role of pancreatic stellate cells (PSCs) in pancreatic cancer ferroptosis is still unclear. Using the coculture system, we revealed that activated PSCs promote pancreatic cancer cell ferroptosis resistance. Mechanistically, activated PSCs secreted HGF, which further activated the HGF receptor, c-MET, in pancreatic cancer cells, prevented lipid peroxidation, and ultimately triggered pancreatic cancer cell ferroptosis resistance in vitro and in vivo. TCGA and GEPIA databases also revealed a strong correlation between c-MET and antiferroptosis indicators. Our study supplied the evidence for the cross-talk between activated PSCs and pancreatic cancer cells in ferroptosis, which suggested a strategy to inhibit PSC paracrine signaling for preventing pancreatic carcinoma ferroptosis resistance.

Background: The Cripto-1 (CR-1)/glucose-regulated protein 78 (GRP78) complex was involved in enhancing survival in different types of cells. CR-1 presented increased levels in ovarian carcinoma tissue. However, the potential mechanism of CR-1/GRP78 was unclear in ovarian cancer. Thus, the study aimed to analyze the role of CR-1/GRP78 in ovarian carcinoma cells. Methods and materials: The CR-1 and GRP78 expression in different ovarian cancer cell lines were detected by RT-qPCR and Western blot (WB). Immunoprecipitation assay was performed to analyze whether Cripto-1 interacted with GRP78. The CR-1 interfering plasmids or GRP-78 overexpressing plasmids transfected into cells were used to decrease endogenous CR-1 levels and increase GRP-78 levels. Cell clonogenicity and proliferation capabilities were separately evaluated by clone growth assay, along with the detection of cell migration and invasion abilities by transwell and wound healing assay. In addition, Matrix Metalloproteinases (MMPs) levels were detected by WB. The cell apoptosis was analyzed by Flow Cytometer and the detection of apoptosis-related proteins. Results: The results showed that CR-1 and GRP78 levels were higher in SKOV3 than other cell lines. Furthermore, CR-1 interacted with GRP78 in cells, which formed protein complex. CR-1 silence significantly decreased GRP-78 levels. Moreover, GRP78 overexpression blocked the anti-survival effects caused by CR-1 knockdown. Conclusion: CR-1 silence inhibited cell proliferation and promoted apoptosis via GRP78. It replied that GRP-78 overexpression might enhance the biological functions of CR-1/GRP78 complex ameliorated by CR-1 silence. Thus, CR-1/GRP78 could be a potential target for treating ovarian carcinoma.

Recent studies have found that hypoxia contributes to tumor progression and drug resistance via inducing exosomes secretion. However, the underlying mechanism of this resistance in pancreatic cancer remains to be explored. In this study, we explored the effect and molecular mechanisms of hypoxia-induced tumor-derived exosomes (Hexo) on stemness and gemcitabine (GEM) resistance in pancreatic cancer cells. Firstly, we discovered that hypoxia could promote the stemness and induce gemcitabine resistance in pancreatic cancer cells. Subsequently, we proved that exosomes secreted by pancreatic cancer cells under normoxic or hypoxic conditions can be transfected into tumor cells. And then, Hexo was demonstrated to promote the proliferation, stemness and Gem resistance of pancreatic cancer cells, as well as inhibit the apoptosis and the cell cycle arrest induced by gemcitabine. Finally, it was verified that Hexo could inactivate the Hippo/YAP pathway of pancreatic cancer cells by transferring exosomal lncROR. In summary, hypoxic tumor microenvironment could promote the stemness and induce gemcitabine resistance in pancreatic cancer cells. Mechanically, Hexo enhanced the stemness to promote chemoresistance of pancreatic cancer cells by transferring lncROR via Hippo signaling. Thus, exosomal lncROR may serve as a candidate target for pancreatic cancer chemotherapy.

Several studies have shown that excessive protein degradation is a major cause of skeletal muscle atrophy induced by sepsis, and autophagy is the main pathway participating in protein degradation. However, the role of autophagy in sepsis is still controversial. Previously, we found that neuregulin-1β (NRG-1β) alleviated sepsis-induced diaphragm atrophy through the phosphatidylinositol-3 kinase signaling pathway. Akt/mechanistic target of rapamycin (mTOR) is a classic signaling pathway to regulate autophagy, which maintains intracellular homeostasis. This study aimed to investigate whether NRG-1β could alleviate sepsis-induced skeletal muscle atrophy by regulating autophagy.L6 rat myoblast cells were differentiated using 2% fetal bovine serum into myotubes, which were divided into four groups: Con group treated with normal serum; Sep group treated with septic serum to form a sepsis cell model; septic serum + NRG-1β (SN) group treated with septic serum for 24 h followed by injection with NRG-1β and incubation for another 48 h; and serum+NRG-1β+LY294002 group, in which the PI3K inhibitor LY294002 was added 30 min before NRG-1β, and other treatments were similar to those in SN group. Effects of NRG-1β were also evaluated in vivo using Sprague-Dawley (SD) rats, in which sepsis was induced by cecal ligation and puncture (CLP).In L6 myotubes treated with septic serum, the expression of autophagy-related proteins UNC-51 like kinase 1, p-Beclin-1, and Beclin-1, and the ratio of LC3B II/I were highly increased, while protein p62 expression was decreased, indicating that autophagy was excessively activated. Moreover, NRG-1 expression was decreased, as detected by confocal immunofluorescence and western blotting. Upon exogenous addition of NRG-1β, autophagy was inhibited by the activation of Akt/mTOR signaling pathway, and cell viability was also increased. These effects disappeared in the presence of LY294002. In SD rats, sepsis was induced by CLP. NRG-1β was shown to inhibit autophagy in these rats via the Akt/mTOR pathway, leading to increased body weight of the septic SD rats and alleviation of atrophy of the tibialis anterior muscle.NRG-1β could alleviate sepsis-induced skeletal muscle atrophy by inhibiting autophagy via the AKT/mTOR signaling pathway.

The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway., Increasing evidence demonstrates that Lin28B plays critical roles in numerous biological processes including cell proliferation and stemness maintenance. However, the molecular mechanisms underlying Lin28B nuclear translocation remain poorly understood. Here, we found for the first time that KRAS promoted Lin28B nuclear translocation through PKCβ, which directly bound to and phosphorylated Lin28B at S243. Firstly, we observed that Lin28B was upregulated in pancreatic cancer, contributing to cellular migration and proliferation. Furthermore, nuclear Lin28B upregulated TET3 messenger RNA and protein levels by blocking the production of mature let‐7i. Subsequently, increased TET3 expression could also promote the expression of Lin28B, thereby forming a Lin28B/let‐7i/TET3 feedback loop. Our results suggest that the KRAS/Lin28B axis drives the let‐7i/TET3 pathway to maintain the stemness of pancreatic cancer cells. These findings illuminate the distinct mechanism of Lin28B nuclear translocation and its important roles in KRAS‐driven pancreatic cancer, and have important implications for development of novel therapeutic strategies for this cancer.

Photothermal ablation could be considered an effective treatment for tumors, but accurate administration and enrichment of photothermal agents remain a huge challenge. Herein, a mussel-inspired photothermal polymeric hydrogel (PPH) was synthesized through a ferric iron-triggered simultaneous metal–catechol coordination reaction and oxidative polymerization of covalently linked pyrrole. The PPH with rapid gelation (less than 10 s) exhibited high photothermal conversion efficiency (49.3%), which enabled effective hyperthermal therapy in situ. Besides, the introduced iron could be used as a T2-weighted contrast agent for real-time MR imaging to explore the retention and bio-degradation of PPH in vivo. Overall, our findings evidence that the resultant PPH, which possesses potential application in tumor ablation in situ, and metal–catechol coordination strategy inspired by mussel adhesion may stimulate biomedical hydrogel development.

Curcumin as a hydrophobic polyphenol has great potential for tumor therapy, yet its rapid degradation and hydrophobicity severely impair its therapeutic effect in the clinic. Herein, we report a novel strategy for the formation of curcumin doped zeolitic imidazolate framework nanoparticles (Cur-ZIF NPs) by zinc ion driven simultaneous coordination of curcumin and 2-methylimidazole. The resultant Cur-ZIF NPs with a uniform nanosize exhibit favorable stability and dispersibility in water, as well as high drug-loading capacities. The pH and redox sensitivity of ZIF NPs enable the controlled release of curcumin

As an emerging discipline, disaster nursing is very important in disaster emergency management, but there are few mature practice models and theoretical discussions. In particular, the contribution of nursing staff in disaster emergency has not yet received widespread attention and recognition. After more than 10 y of rapid development, China’s disaster nursing has gradually formed a Chinese model and Chinese experience. During the global fight against coronavirus disease 2019 (COVID-19), this article takes the nursing work in disaster emergency rescue as the perspective and briefly describes the development process of disaster nursing in China to introduce the practice and theoretical development of disaster nursing in China to nursing workers around the world. Analyzing the role of Chinese nurses in national disaster emergency response provides a reference for global disaster nursing talent capacity building. By sharing the Nightingale spirit of Chinese nurses in disaster emergency, we will show people all over the world the professional value of disaster nursing practitioners and pay tribute to the nursing staff engaged in disaster emergency work.

Ferroptosis, a form of iron-dependent cell death driven by cellular metabolism and iron-dependent lipid peroxidation, has been implicated as a tumor-suppressor function for cancer therapy. Recent advance revealed that the sensitivity to ferroptosis is tightly linked to numerous biological processes, including metabolism of amino acid and the biosynthesis of glutathione. Here, by using a high-throughput CRISPR/Cas9-based genetic screen in HepG2 hepatocellular carcinoma cells to search for metabolic proteins inhibiting ferroptosis, we identified a branched-chain amino acid aminotransferase 2 (BCAT2) as a novel suppressor of ferroptosis. Mechanistically, ferroptosis inducers (erastin, sorafenib, and sulfasalazine) activated AMPK/SREBP1 signaling pathway through iron-dependent ferritinophagy, which in turn inhibited BCAT2 transcription. We further confirmed that BCAT2 as the key enzyme mediating the metabolism of sulfur amino acid, regulated intracellular glutamate level, whose activation by ectopic expression specifically antagonize system Xc– inhibition and protected liver and pancreatic cancer cells from ferroptosis in vitro and in vivo. On the contrary, direct inhibition of BCAT2 by RNA interference, or indirect inhibition by blocking system Xc– activity, triggers ferroptosis. Finally, our results demonstrate the synergistic effect of sorafenib and sulfasalazine in downregulating BCAT2 expression and dictating ferroptotic death, where BCAT2 can also be used to predict the responsiveness of cancer cells to ferroptosis-inducing therapies. Collectively, these findings identify a novel role of BCAT2 in ferroptosis, suggesting a potential therapeutic strategy for overcoming sorafenib resistance.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Emerging evidence indicates that tumour cells release substantial amounts of RNA into the bloodstream, in which RNA strongly resists RNases and is present at sufficient levels for quantitative analyses. Our study aimed to discover blood-based markers for the early detection of CRC and to ascertain their efficiency in discriminating healthy controls, patients with polyps and adenomas and cancer patients. We first analysed and screened ZFAS1, SNHG11, LINC00909 and LINC00654 in a bioinformatics database and then collected clinical plasma samples for preliminary small-scale analysis and further large-scale verification. We then explored the mechanism of dominant lncRNA SNHG11 expression in CRC by in vitro and in vivo assays. The combination of ZFAS1, SNHG11, LINC00909 and LINC00654 showed high diagnostic performance for CRC (AUC: 0.937), especially early-stage disease (AUC: 0.935). Plasma levels of the four candidate lncRNAs were significantly reduced in postoperative samples compared to preoperative samples. A panel including these four lncRNAs performed well in distinguishing patient groups with different stages of colon disease, and SNHG11 exhibited the greatest diagnostic ability to identify precancerous lesions and early-stage tumour formation. Mechanistically, high SNHG11 expression promotes proliferation and metastasis by targeting the Hippo pathway. Taken together, the data indicate that SNHG11 may be a novel therapeutic target for the treatment of CRC and a potential biomarker for the early detection of CRC.

Hypochlorite (ClO-) and singlet oxygen (1O2) commonly coexist in living systems and exert important interplaying roles in many diseases. To dissect their complex inter-relationship, it is urgently required to construct a fluorescent probe that can discriminate ClO- and 1O2 in living organisms. Herein, by taking the 3-(aliphaticthio)-propan-1-one group as the unique recognition unit for both ClO- and 1O2, we proposed the first fluorescent probe, Hy-2, to simultaneously discriminate ClO- and 1O2 with high sensitivity and selectivity. Probe Hy-2 itself showed fluorescence in blue channel. After treatment with ClO- and 1O2, respectively, pronounced fluorescence enhancements were observed in the green channel and red channel correspondingly. Moreover, upon development of the probe with aggregation-induced emission (AIE) characteristics, the probe could work well in a solution with high water volume fraction. Probe Hy-2 was also able to accumulate into mitochondria and was utilized as an effective tool to image exogenous and endogenous ClO- and 1O2 in mitochondria. Significantly, as the first trial, probe Hy-2 was employed to simultaneously monitor the variation of ClO- and 1O2 level in cecal tissues of rat in the cecal ligation and puncture (CLP)-induced polymicrobial sepsis model. The results demonstrated that the expressed ClO- and 1O2 levels were tightly correlated with the severity of sepsis, inferring that the overproduction of ClO- and 1O2 is an important factor in the pathogenesis of sepsis. The probe illustrated herein may provide a guide for further exploring the functions of ClO- and 1O2 in various diseases.

Photothermal therapy (PTT) causes immunogenic tumor cell death (ICD), while fails to elicit a strong anti-tumor immune response partially due to its inherent immunosuppressive microenvironment and low antigen presentation. To address these issues, we developed an immunoinducible carbon dots-incorporated hydrogels (iCD@Gel) through a dynamic covalent Schiff base reaction using mannose modifed aluminum-doped carbon dots (M/A-CDs) as cross-linking agent. The M/A-CDs not only possessed superior photothermal conversion efficiency, but also served as nanocarrier to load CpG ODNs for inducing the maturation of dendritic cells (DCs) via manose receptor-mediated targeting delivery. Upon intratumoral injection, the as-prepared iCD@Gel induced immunogentic tumor cell death and damage-related molecular patterns (DAMPs) release via photothermal ablation under 808 nm NIR irradiation. Subsequently, the iCD@Gel synergized with the DAMPs to significantly promote the maturation and antigen cross-presentation of DCs. Taken together, this work provides a promising strategy to develop nanoparticle-based therapetuic hydrogel for tumor immunotherapy.

Fluorescence imaging the interplay between lipid droplets (LDs) and protein aggregates (PAs) is extremely valuable for elucidating molecular mechanisms of aging. Here, we describe the first dual-functional fluorescent probe

Ferroptosis is a type of regulated cell death that displays a promising therapeutic pathway for drug-resistant tumor cells. However, some pancreatic cancer (PC) cells are less sensitive to erastin-induced ferroptosis, and normal pancreatic cells are susceptible to this newly discovered cell death. Therefore, there is an urgent need to find drugs to enhance the sensitivity of these PC cells to erastin while limiting side effects. Here, we found that the oxidized form of vitamin C-dehydroascorbic acid (DHA) can be transported into PC cells expressing high levels of GLUT1, resulting in ferroptosis. Moreover, pharmacological vitamin C combined with erastin can synergistically induce ferroptosis of PC cells involving glutathione (GSH) reduction and ferrous iron accumulation while inhibiting the cytotoxicity of normal cells. Mechanistically, as a direct system Xc- inhibitor, erastin can directly suppress the synthesis of GSH, and the recycling of vitamin C and DHA is performed through GSH consumption, which is denoted as the classical mode. Furthermore, oxidative stress induced by erastin and vitamin C could enhance the expression of HMOX1 via the AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway to increase the labile iron level, which is named the nonclassical mode. In vivo experiments showed that erastin and vitamin C can significantly slow tumor growth in PC xenografts. In summary, the combination of erastin and vitamin C exerts a synergistic effect of classical and nonclassical modes to induce ferroptosis in PC cells, which may provide a promising therapeutic strategy for PC.

Background Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice. Methods Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment. Results Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days’ treatment (p p p Conclusions NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK.

In order to cultivate the ability of independent learning and lifelong learning of medical students, improve the ability of students to analyze and solve problems, improve the competence of medical talents and cultivate high-level and innovative talents, we have constructed the blended teaching model of "Clinical Case Investigation-Online Open Course Learning-Classroom PBL Seminar-After-Class Health Education". At the same time, an ability-oriented performance evaluation system improved the teaching quality feedback system has also established. This article introduces the construction and application of the blended teaching model, as well as the problems it faces, provides a theoretical basis for the optimization and improvement of this model. It also provides a model theory and practical basis for creating a blended online and offline "golden course" for the professional courses of medical laboratory technology.

The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as well as its association with intestinal barrier function. In this study, C57BL/6J mice were fed different concentrations of NMN, and their feces were collected for detection of 16S rDNA and non-targeted metabolites to explore the effects of NMN on intestinal microbiota and metabolites. The results revealed that NMN increased the abundance of butyric acid-producing bacteria (Ruminococcae_UCG-014 and Prevotellaceae_NK3B31_group) and other probiotics (Akkermansia muciniphila), while the abundance of several harmful bacteria (Bilophila and Oscillibacter) were decreased after NMN treatment. Meanwhile, the level of bile acid-related metabolites in feces from the G1 group (0.1 mg/ml) was significantly increased compared to the control group, including cholic acid, taurodeoxycholic acid, taurocholic acid, glycocholic acid, and tauro-β-muricholic acid. In addition, long-term NMN treatment affected the permeability of the intestinal mucosa. The number of goblet cells and mucus thickness increased, as well as expression of tight junction protein. These results demonstrate that NMN reduced intestinal mucosal permeability and exerts a protective effect on the intestinal tract. This study lays the foundation for exploring NMN's utility in clinical research.

Protein arginine methyltransferase 5 (PRMT5) has been implicated in the development and progression of human cancers. However, few studies reveal its role in epithelial‐mesenchymal transition (EMT) of pancreatic cancer cells. In this study, we find that PRMT5 is up‐regulated in pancreatic cancer, and promotes proliferation, migration and invasion in pancreatic cancer cells, and promotes tumorigenesis. Silencing PRMT5 induces epithelial marker E‐cadherin expression and down‐regulates expression of mesenchymal markers including Vimentin, collagen I and β‐catenin in PaTu8988 and SW1990 cells, whereas ectopic PRMT5 re‐expression partially reverses these changes, indicating that PRMT5 promotes EMT in pancreatic cancer. More importantly, we find that PRMT5 knockdown decreases the phosphorylation level of EGFR at Y1068 and Y1172 and its downstream p‐AKT and p‐GSK3β, and then results in down‐regulation of β‐catenin. Expectedly, ectopic PRMT5 re‐expression also reverses the above changes. It is suggested that PRMT5 promotes EMT probably via EGFR/AKT/β‐catenin pathway. Taken together, our study demonstrates that PRMT5 plays oncogenic roles in the growth of pancreatic cancer cell and provides a potential candidate for pancreatic cancer treatment.

Large intergenic noncoding RNA regulator of reprogramming (Linc-RoR) was first identified as a regulator to increase the emergence of induced pluripotent stem cells through reprogramming differentiated cells and is abnormal expression in a variety of malignant tumors. However, the function of Linc-RoR in pancreatic cancer progression needs further clarification. The data from this study demonstrated that Linc-RoR knockdown suppressed cell proliferative capacity and colony formation, while Linc-RoR overexpression promoted these behaviors. In particular, Linc-RoR overexpression promoted the level of mesenchymal markers, inhibited the expression of epithelial markers, as well as enhanced pancreatic cancer cells migration and invasion, whereas Linc-RoR knockdown inhibited the expression of mesenchymal markers, promoted the expression of epithelial markers, as well as weakened pancreatic cancer cells migration and invasion. Further study revealed that Linc-RoR knockdown brought about a significant fall in YAP phosphorylation and a rise in total YAP, while Linc-RoR overexpression produced the opposite results. Specifically, Linc-RoR promoted YAP in the cytoplasm into the nucleus. Taken together, we conjectured that Linc-RoR promoted proliferation, migration, and invasion of pancreatic cancer cells by activating the Hippo/YAP pathway. YAP might be an underlying target of Linc-RoR and mediate epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC); thus, Linc-RoR might be a very meaningful biomarker for PC.

Objective: To investigate the exact role of GRP78 in artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells. Methods: Artesunate-induced KRAS mutant human pancreatic cancer cells (AsPC-1 and PaTU8988) ferroptosis was confirmed by fluorescent staining experiments and CCK8. Western blot and short-hairpin RNA-based knockdown assays were conducted to detect GRP78 activity and its role in artesunate-induced ferroptosis. Results: Artesunate induced AsPC-1 and PaTU8988 cell death in ferroptosis manner, rather than necrosis or apoptosis. In addition, artesunate increased the mRNA and protein levels of GRP78 in a concentration-dependent manner in AsPC-1 and PaTU8988 cells. Knockdown GRP78 enhanced artesunate-induced ferroptosis of pancreatic cancer cells in vitro and in vivo. Conclusion: Combining artesunate with GRP78 inhibition may be a novel maneuver for effective killing of KRAS mutant pancreatic ductal adenocarcinoma cells.

Fengyi Du,*,1,2 Yunchao Wu,*,2 Fengting Du,*,3 Lirong Zhang,3 Weiwei Feng,4 Lulu Zhao,2 Rong Cai,3 Lixia Xu,2 Gaorui Bian,5 Jiangang Li,5 Shengqiang Zou,1 Aihua Gong,2 Miaomiao Zhang21Department of Hepatosis, The Affiliated Third Hospital of Zhenjiang, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2School of Medicine, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 3Department of Physiotherapy, Huangnihe Town Hospital, Huangnihe 133704, People’s Republic of China; 4School of Environmental and Safety Engineering, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 5Tianyi Health Sciences Institute (Zhenjiang) Co. Ltd, Zhenjiang 212013, People’s Republic of China*These authors contributed equally to this workBackground: The gastroretentive drug delivery system is an effective administration route, which can improve the bioavailability of the drug and the therapeutic effect by prolonging the release time of the drug and controlling the release rate in the stomach.Methods: Inspired by the excellent adhesion properties of mussel protein, we prepared novel catechol-grafted chitosan alginate/barium sulfate microcapsules (Cat-CA/BS MCs) with mucoadhesive properties and computed tomography (CT) imaging function for gastric drug delivery. First, barium sulfate nanoclusters used as CT contrast agent were synthesized in situ in the Cat-CA/BS MCs through a one-step electronic spinning method. Next, catechol-grafted chitosan as the mucoadhesive moiety was coated on the surface of Cat-CA/BS MCs by polyelectrolyte molecule self-assembly.Results: The prepared Cat-CA/BS MCs could effectively retained in the stomach for 48 hours and successively released ranitidine hydrochloride, which could be used for the treatment of gastric ulcer. Cat-CA/BS MCs exhibited superior CT contrast imaging properties for real-time tracking in vivo after oral administration.Conclusion: These findings demonstrate that Cat-CA/BS MCs serving as multifunctional oral drug carriers possess huge potential in gastroretentive drug delivery and non-invasive visualization.Keywords: catechol, mucoadhesive, microcapsules, CT imaging, gastroretentive drug delivery

Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.

Magnetic resonance imaging (MRI) contrast agents (CTs) with both positive (T1) and negative (T₂) contrast abilities have attracted considerable interests due to their complementary diagnostic information for more precise diagnosis. In this study, gadolinium-doped oxide nanoparticles functionalized by hyaluronic acid (HA-GdIO NPs) were synthesized for atherosclerosis-targeting T1-T₂ dual-model MR imaging. The results showed that the HA-GdIO NPs exhibited high magnetic susceptibility and good biocompatibility. After being coated with HA, the HA-GdIO NPs specifically accumulated in the atherosclerosis plaques through targeting CD44-overpression macrophages which played a central role in development of atherosclerotic plaques. Furthermore, the HA-GdIO NPs can provide enhanced T1 and T₂ dual phase contrast effects in vitro and in vivo, particularly in the vascular regions of mice. This work may provide a promising idea to construct MRI contrast agents with both effective and targeted contrast abilities for biomedical applications.

Background Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

Tumor recurrence after the clinical cure of tumor often results from the presence of an abnormal microenvironment, including an aberrant vasculature. The tumor microenvironment is rich in pro-angiogenic factors but lacks pro-maturation factors. Pro-angiogenic conditions in the tumor microenvironment, such as hypoxia, are double-edged swords, promoting both the repair of normal tissues and the development of an abnormal blood vessel network. The coexistence of perfusion and hypoxic zones and uneven blood vessel distribution in tumor tissues profoundly influence tumor deterioration, recurrence, and metastasis. Traditional anti-angiogenic therapies have shown limited efficacy, and promote drug resistance, and even metastasis. In contrast, vascular normalization therapy induces a more physiological-like state, leading to better outcomes and fewer side effects. Vascular normalization entails modifying the tumor vascular system to improve tumor oxygenation and substance transport, thereby contributing to improving the efficacy of radiotherapy, chemotherapy, and immunotherapy. This review mainly focuses on the process of tumor vascularization; potential therapeutic targets, including cells, metabolism, signaling pathways, and angiogenesis-related genes; and possible strategies to normalize blood vessels through regulating tumor vessel generation, the development of tumor vessels, and blood vessel fusion and pruning.

Photothermal ablation could be considered an effective treatment for tumors, but accurate administration and enrichment of photothermal agents remain a huge challenge. Herein, a mussel-inspired photothermal polymeric hydrogel (PPH) was synthesized through a ferric iron-triggered simultaneous metal-catechol coordination reaction and oxidative polymerization of covalently linked pyrrole. The PPH with rapid gelation (less than 10 s) exhibited high photothermal conversion efficiency (49.3%), which enabled effective hyperthermal therapy