Table_1_A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer.XLSX

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.</p

Data_Sheet_1_A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer.docx

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.</p

Image_3_A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer.TIF

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.</p

Image_1_A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer.TIF

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.</p

Image_2_A prognostic signature based on cuprotosis-related long non-coding RNAs predicts the prognosis and sensitivity to chemotherapy in patients with colorectal cancer.TIF

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.</p

Porous Polylactide Film Plus Atorvastatin-Loaded Thermogel as an Efficient Device for Peritoneal Adhesion Prevention

Peritoneal adhesion is a common postoperative complication that causes many kinds of organ dysfunctions. It can be minimized by the integration of physical isolation and pharmaceutical treatment. However, the gas permeability of traditional medical devices for adhesion prevention is not satisfactory, which increases the risk of infection and inflammation, thus facilitating the formation of peritoneal adhesion. In this study, a device of porous polylactide (PLA) film plus atorvastatin (ATV)-loaded thermogel was developed for peritoneal adhesion prevention. PLA film acted as a physical barrier to prevent the connection of fibrin bridges between the injured tissues and nearby normal organs. Simultaneously, ATV was released to achieve the antifibrin deposition and anti-inflammatory effect. The porous properties of PLA film and thermogel increased the gas permeability and further inhibited the inflammatory responses. The in vivo study demonstrated that the porous PLA film with ATV-loaded thermogel possessed excellent anti-inflammation ability and satisfactory antiadhesion capacity, indicating its great potential for clinical application

Locally Deployable Nanofiber Patch for Sequential Drug Delivery in Treatment of Primary and Advanced Orthotopic Hepatomas

With unsatisfactory effects of systemic chemotherapy for treatment of unresectable or advanced hepatoma, local and sustained delivery of chemotherapeutic agents is becoming a promising solution. The <i>in situ</i> administered platforms increase the drug concentrations in tumor regions, decrease the side effects to organs, prevent the damage to vascular endothelium, and reduce the frequency of drug administration. The prevalent strategy based on minimally invasive transarterial chemoembolization oftentimes induces upper gastrointestinal hemorrhage, liver failure, and liver abscess. In addition, integrating various antitumor drugs in one platform, especially the drugs with different hydrophilic/hydrophobic properties, and achieving sustained and/or sequential release profiles to synergistically inhibit cancer progression remain challenging. In this study, a local drug delivery system made of an emulsion-electrospun polymer patch was developed, which contained hydrophobic 10-hydroxycamptothecin (HCPT) and hydrophilic tea polyphenols (TP) in the shell and core of the nanofiber, respectively. Due to this core–sheath structure, HCPT and TP exhibited sustained and sequential releases first with HCPT followed by TP. HCPT was used to suppress the proliferation and malignant transformation of hepatoma, whereas TP was aimed to decrease the levels of oxygen free radicals and further prevent the invasion and metastasis of tumor cells. Our study presented the potential superiority of this class of core–sheath structured nanofiber membranes in localized treatment of both primary and advanced orthotopic hepatomas

A late Neoarchean continental arc system in the northeastern North China Craton: constrain from the Guanghua mélange in the Tonghua area, southern Jilin Province

The late Neoarchean tonalite – trondhjemite – granodiorite (TTG) and mafic rocks record essential information regarding the early tectonic evolution of the North China Craton, which is crucial for understanding the onset and development of the plate tectonic regime. In this study, we present a comprehensive analysis of petrography, geochronology, and geochemistry of the Guanghua Mélange from the Tonghua area in NE China. The mélange comprises basalt, gabbro, pyroxene diorite, and trondhjemite, and is classified into three groups: basaltic – gabbroic rocks (Group #1), dioritic rocks (Group #2), and trondhjemites (Group #3). Zircon U-Pb analyses indicate that they formed at 2596–2550 Ma, 2531–2515 Ma, and 2502 Ma, respectively, with metamorphism occurring during ~ 2500–2450 Ma. Meanwhile, geochemical data indicate that the calc – alkaline basaltic rocks (Group #1) exhibit slight depletion of Nb or Ta with weakly negative Eu anomalies, suggesting derivation from the lithospheric mantle and formation within a continental arc environment. The pyroxene diorites (Group #2) display similar geochemical characteristics to Group #1, likely formed by partial melting of depleted mantle that underwent sgignificant metasomatism due to variable amounts of slab-derived fluids or melts. The tholeiitic granitoids (Group #3) exhibit strongly fractionated chondrite-normalized REE patterns with high (La/Yb)N and Sr contents, low Y contents, and depletion of Nb, Ta or Ti, resembling adakites generated in arc setting, indicating likely formation through partial melting of subducted oceanic crust. This process was controlled by the initial plate tectonics under a higher geothermal gradient. Consequently, when combined with previous findings, we conclude that an initial subduction of oceanic plate operated in the northeastern North China Craton during the late Neoarchean (>2.55 Ga). Subsequently, it transformed into modern-type plate tectonics during ~ 2.55–2.53 Ga, eventually followed by the continent-continent collision at ~ 2.50–2.45 Ga, resulting in the formation of the Ji – Liao – Ji (Jilin – Liaoning – Hebei) Collision Orogenic Belt.</p

PP242 and erlotinib treatment induce apoptotic cell death.

<p>(A) DLD-1 cells were treated with erlotinib (2 μM) and PP242 (1 μM), alone or in combination, for the indicated hours and then analyzed by flow cytometry. The percentage of sub-G1 apoptotic cells were presented as mean <u>+</u> SD. **, p < 0.01. (B) DLD-1 cells were treated with PP242 (1 μM) and/or erlotinib (2 μM) for the indicated hours and analyzed by western blotting for the cleavage of caspase-3, DFF45 and PARP with the molecular weights of the cleavage products indicated to the right of the panel.</p

Highly Bioadhesive Polymer Membrane Continuously Releases Cytostatic and Anti-Inflammatory Drugs for Peritoneal Adhesion Prevention

Peritoneal adhesion is a complex fibrosis and inflammatory process, and it can be minimized by physical isolation by biomaterial membranes or treatment with cytostatic and/or anti-inflammatory drugs. However, the integration of physical isolation and pharmaceutical therapy in one platform faces many challenges. First, normal polymer antiadhesion membranes are hydrophobic and show low bioadhesion to the injured tissue, which decrease their efficacies. Second, the significantly different release behaviors of various drugs owing to their different hydrophilic/hydrophobic properties limit their synergistic effects. In this study, a highly bioadhesive polymer membrane formed by core–sheath nanofiber to integrate physical isolation and pharmaceutical treatment together for the synergistic prevention of peritoneal adhesion. 10-Hydroxycamptothecin (HCPT) and diclofenac sodium (DS) were loaded in the sheath and core of nanofiber, respectively. The membrane was then treated by ultraviolet-ozone (UVO) for improvement of hydrophilicity and bioadhesion. Owing to the core–sheath structure, the two drugs both performed a sustained release behavior for the cytostatic and anti-inflammatory effects. The in vivo study demonstrated that the UVO-treated and dual-drug-coloaded membrane possessed the best antiadhesion capacity, indicating its potential clinical application