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Abstract The tumor microenvironment (TME) is pivotal in non-small cell lung cancer (NSCLC) progression, influencing drug resistance and immune cell behavior through complex ligand-receptor (LR) interactions. This study developed an epithelial LR-related prognostic risk score (LRrisk) to identify biomarkers and targets in NSCLC. We identified twenty epithelial LRs with significant prognostic implications and delineated three molecular NSCLC subtypes with distinct outcomes, pathological characteristics, biological pathways, and immune profiles. The LRrisk model was constructed using twelve differentially expressed ligand-receptor interaction-related genes (LRGs), with a focus on POPDC3 (popeye domain-containing protein 3), which was overexpressed in NSCLC cells. Functional assays revealed that POPDC3 knockdown reduced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while its overexpression promoted cancerous activities. In vivo, POPDC3 silencing hindered, and its overexpression accelerated the growth of NSCLC xenografts in nude mice. Additionally, high expression levels of POPDC3 in NSCLC tissues were associated with enhanced CD4+ T cell infiltration and increased PD-1 expression within the TME. Moreover, ectopic POPDC3 overexpression in C57BL/6 J mouse Lewis lung carcinoma (LLC) xenografts enhanced CD4+ T cell infiltration and PD-1 expression in the TME. This research establishes a robust epithelial LR-related signature, highlighting POPDC3 as a critical facilitator of NSCLC progression and a potential therapeutic target.

Abstract Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post‐surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti‐recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti‐recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.

In China, solid waste backfill technology has been used in metal mines for more than half a century. It has been essential for comprehensive excavation and utilization of mineral resources, environmental protection, and engineering safety. The core concept of solid waste filling has not changed qualitatively despite the rapid development of mining technology from semi-mechanized and mechanized automation and intelligence. It is mainly used in mine tailings, waste rock, and other solid wastes to control the hazards of goaf and tailings reservoir from the source to treat waste and hazards. However, the quality requirements, degree of fine control, and intelligent allocation technology of solid waste filling are undergoing considerable changes. Furthermore, the design philosophy of modern backfill technology consider comprehensive realization of solid waste utilization, environment conservation, mined-out area disposal, resource recovery, and ground pressure control that require optimal backfill method, sufficient mechanical strength, and pumpable backfill slurry, using information technology, automatic technology, and equipment technology. Besides, new backfill concepts are introduced, such as collaborative paste and multimaterial, synchronous, and functional backfills. In this paper, the framework of backfill mechanics was described, relying on rheology and solid mechanics. The influences of in-situ multifield factors were analyzed based on the characteristics of the in-situ stope, introducing the latest multifield coupling monitoring system. More details about the development trend and research status of critical processes in the backfill, including deep thickening, mixing, and long-distance pipe transport, have been updated. We propose a picture for the future development of intelligent backfill based on the advantages of intelligent backfill and performance of intelligent algorithms in the backfill field. In terms of the future trend of solid waste backfill, we feel that it can enrich green mining, explore the realization of modular, scale, and intelligent backfill, and actively examine and serve the needs of deep mining. Thus, the backfill method appears as the optimal choice for deep mining and green mining.

Abstract Background Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis. Methods Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content. Results Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P

Ultrasound-assisted enzymolysis has been applied to improve conventional enzymolysis, while there are rare reports on the application of ultrasound to high-concentration feather protein enzymolysis. Therefore, the feasibility of dual-frequency slit ultrasound (DFSU) for enzymolysis of high-concentration hydrolyzed feather meal (HFM), as well as the biological activities and structural characteristics of hydrolysates were investigated. The single-factor test was used to optimize the ultrasonic processing parameters: substrate concentration, frequency mode, intermittent ratio, power density, and time. The results showed that protein recovery rate and conversion rate increased by 6.08% and 18.63% under the optimal conditions (200 g/L, 28/80 kHz, 5:2 s/s, 600 W/L, and 3 h) compared with conventional enzymolysis, respectively. The macromolecular proteins in hydrolysates were converted into micromolecular peptides (< 500 Da) when treated by DFSU, and antioxidant activity and angiotensin-I-converting enzyme (ACE) inhibitory activity of hydrolysates were increased. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) images illustrated the microstructure changes of feather protein particles in the ultrasound-assisted enzymatic hydrolysates of HFM (UEH), including more porous, smaller, and more uniform. Additionally, the conformation of protein molecules was significantly affected (P

BackgroundLiver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients’ prognosis prediction.MethodsWe collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1.ResultsAccording to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA.ConclusionOur study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC.

Nanozyme has been experiencing rapid development in biomedical applications involving biosensors, immunoassays, and antitumor agents in recent years due to its tunable catalytic performance and desirable biocompatibility. Since the first exploration of nanozyme‐based Fenton reaction for nanocatalytic therapy (NCT) against tumor, a variety of Fenton (and Fenton‐like) nanozymes, such as Fe3O4, transition metal ions (Co2+, Cu2+, and Mn2+), and metal–organic frameworks (MOFs), have been proved as desirable candidates for tumor therapy, and the modulation of the tumor microenvironment (TME) is determined to be a feasible approach to improve the catalytic efficiency for in situ tumor suppression. At present, increasing studies have focused on improving the therapeutic efficiency of NCT by formulating multifunctional nanozyme‐based systems to satisfy the demand for versatile and optimized applications. Herein, updated insights into the novel strategies of 1) achieving highly effective nanocatalytic reactions, including the modification of nanocatalysts and TME‐modulating approaches, are provided and 2) the design and formulation of multifunctional nanozyme‐based systems which achieve targeted, synergistic therapy, and theranostic applications are analyzed and concluded. Concise and concentrated comments and outlooks are illuminated at the end to outline the perspectives and the remaining challenges for the next‐step explorations on further biomedical translation of NCT.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide, which lacks effective inhibition of progression and metastasis in the advanced clinical stage. Mesoporous silica nanoparticle (MSN)–based cytotoxic or immunoregulatory drug–loading strategies have attracted widespread attention in the recent years. As a representative of mesoporous biomaterials, MSNs have good biological characteristics and immune activation potential and can cooperate with adjuvants against HCC. This review summarizes the possible future development of the field from the perspective of tumor immunity and aims to stimulate the exploration of the immune mechanism of MSN-based therapy. Through this point of view, we hope to develop new clinical immune drugs that can be applied to HCC clinical management in the future.

Primary liver cancer is the seventh-most-common cancer worldwide and the fourth-leading cause of cancer mortality. In the current era of precision medicine, the diagnosis and management of liver cancer are full of challenges and prospects. Mesoporous nanoparticles are often designed as specific carriers of drugs and imaging agents because of their special morphology and physical and chemical properties. In recent years, the design of the elemental composition and morphology of mesoporous nanoparticles have greatly improved their drug-loading efficiency, biocompatibility and biodegradability. Especially in the field of primary liver cancer, mesoporous nanoparticles have been modified as highly tumor-specific imaging contrast agents and targeting therapeutic medicine. Various generations of complexes and structures have been determined for the complicated clinical management requirements. In this review, we summarize these advanced mesoporous designs in the different diagnostic and therapeutic fields of liver cancer and discuss the relevant advantages and disadvantages of transforming applications. By comparing the material properties, drug-delivery characteristics and application methods of different kinds of mesoporous materials in liver cancer, we try to help determine the most suitable drug carriers and information media for future clinical trials. We hope to improve the fabrication of biomedical mesoporous nanoparticles and provide direct evidence for specific cancer management.

This paper aims to provide a stable instrumental method for provenance discrimination of Anji-White tea by its distinctive taste. 180 authentic and 60 counterfeit white tea samples were collected for specific geographical origins detection; all of them were measured by electronic tongue coupled with 7 independent sensors. Therefore, chemometrics methods, principal component analysis (PCA), and partial least squares discriminant analysis (PLSDA) were performed in classification. The PCA distribution shows that, in provenance analysis, PCA is a simple and reliable tool for small sample sets, but for sets with large objects, PCA seems powerless in classification. Therefore, PLSDA was applied to develop a classification model. The prediction sensitivity and specificity of PLSDA, respectively, reached 0.917 and 0.950. This study demonstrates the potential of combining electronic tongue system and chemometrics as an effective tool for specific geographical origins detection in Anji-White tea.

Due to their excellent properties and two-dimensional geometry, graphenes (Grs) have been widely used as reinforced fillers in graphene/aluminum nanolaminated composite (GANC). The separation and slippage behavior of the GANC is highly dependent on the interfacial properties between Gr and aluminum (Al). In this study, two interfacial failures of GANCs, i.e., pull-up failure and pull-out failure, were investigated using a molecular dynamics (MD) method. The effects of the crystal orientation of single-crystal Al component and the geometry of the Gr component on the normal and shear interfacial properties of the GANC were examined. It was evident that the interfacial pull-up resistance resulted from the atomic forces of all the atoms at the interface, whereas the interfacial shear force during pull-out stems from the atomic forces of the atoms at the crack tip. In addition, the studies revealed that the interface bonding strength between the Gr and Al was sensitive to both the crystal orientation of the Al and the environmental temperature. Finally, the cohesive law was used to describe the interfacial behavior of the Gr and Al, providing the interfacial data for the finite element modeling of composites with Gr and Al interface.