Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Synthesis of Photoresponsive Fast Self-healing Polyolefin Composites by Nickel-Catalyzed Copolymerization of Ethylene and Lignin Cluster Monomers.

Polymers may suffer from sudden mechanical damages during long-term use under various harsh operating environments. Rapid and real-time self-healing will extend their service life, which is particularly attractive in the context of circular economy. In this work, a lignin cluster polymerization strategy (LCPS) was designed to prepare a series of lignin functionalized polyolefin composites with excellent mechanical properties through nickel catalyzed copolymerization of ethylene and lignin cluster monomers. These composites can also achieve rapid self-healing within 30 seconds under a variety of extreme usage environments (underwater, seawater, extremely low temperatures as low as -60 °C, organic solvents, acid alkali solvents, etc.), which is of great significance for real-time self-healing of sudden mechanical damage. More importantly, the dynamic cross-linking network within these composites enable great re-processability and amazing sealing performances.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Metastatic clear cell sarcoma of the pancreas: A rare case report.

BACKGROUND: Clear cell sarcoma (CCS) is a rare soft-tissue sarcoma. The most common metastatic sites for CCS are the lungs, bones and brain. CCS is highly invasive and mainly metastasizes to the lung, followed by the bone and brain; however, pancreatic metastasis is relatively rare. CASE SUMMARY: We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man. The patient had a relevant medical history 3 years ago, with abdominal pain as the main clinical manifestation. No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography. Based on the medical history and postoperative pathology, the patient was diagnosed with CCS with pancreatic metastasis. The patient was successfully treated with surgical interventions, including distal pancreatectomy and splenectomy. CONCLUSION: This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.

Association Between Pretreatment Blood 25-Hydroxyvitamin D Level and Survival Outcomes in Patients With Clinically Localized Prostate Cancer: An Updated Meta-Analysis.

Studies on the prognostic value of the blood 25-hydroxyvitamin D level have yielded controversial results in prostate cancer (PCa) patients. This updated meta-analysis aimed to evaluate the association between pretreatment 25-hydroxyvitamin D level with survival outcomes among patients with clinically localized PCa. PubMed, Web of Science, and Embase databases were searched to identify studies evaluating the association of pretreatment 25-hydroxyvitamin D level with PCSM and all-cause mortality among clinically localized PCa patients. Ten cohort studies with 10,394 patients were identified. The meta-analysis revealed that PCa patients with the lowest 25-hydroxyvitamin D levels had an increased risk of PCSM (adjusted hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.26-1.83; p < 0.001) and all-cause mortality (adjusted HR 1.31; 95% CI 1.00-1.90; p = 0.047) compared to those with higher reference 25-hydroxyvitamin D level. Subgroup analyses based on different sample sizes, follow-up duration, and adjusted times of blood draw also exhibited a significant association of vitamin D deficiency with the risk of PCSM. Lower pretreatment level of 25-hydroxyvitamin D may be an independent predictor of reduced survival in patients with clinically localized PCa. Measuring the pretreatment blood 25-hydroxyvitamin D level can provide valuable information for risk stratification of survival outcomes in these patients.

Pretreatment prostate-specific antigen density as a predictor of biochemical recurrence in patients with prostate cancer: a meta-analysis.

BACKGROUND: A consensus has not been reached on the value of prostate-specific antigen density (PSAD) as a predictor of biochemical recurrence of prostate cancer. This meta-analysis aimed to evaluate the association between PSAD and biochemical recurrence of prostate cancer after primary treatment. METHODS: Two authors systematically searched PubMed, Web of Science, and Embase databases (up to August September 10, 2023) to identify studies that assessed the value of pretreatment PSAD in predicting biochemical recurrence after primary treatment (radical prostatectomy or radiotherapy) of prostate cancer. A random effect model was used to pool adjusted hazard ratios (HR) with 95% confidence intervals (CI) for biochemical recurrence. RESULTS: Nine studies with 4963 patients were eligible for the meta-analysis. The reported prevalence of biochemical recurrence ranged from 4 to 55.1%. For patients with higher PSAD compared to those with low PSAD, the pooled HR of biochemical recurrence was 1.59 (95% CI 1.21-2.10). Subgroup analysis showed that the pooled HR of biochemical recurrence was 1.80 (95% CI 1.34-2.42) for patients who received radical prostatectomy, and 0.98 (95% CI 0.66-1.45) for patients who received radiotherapy. CONCLUSIONS: Elevated pretreatment PSAD may be an independent predictor for biochemical recurrence of prostate cancer after radical prostatectomy. Determining PSAD could potentially improve the prediction of biochemical recurrence in patients with prostate cancer.

Association between Charlson comorbidity index and survival outcomes in patients with prostate cancer: A meta-analysis.

Objective: This meta-analysis aimed to assess the influence of comorbidity, as assessed by the Charlson comorbidity index (CCI), on survival outcomes in patients with prostate cancer (PCa). Methods: We conducted a comprehensive search of the PubMed, Web of Science, and Embase databases to identify studies that examined the association between CCI-defined comorbidity and survival outcomes in PCa patients. We employed a random effect model to merge adjusted hazard ratios (HR) with 95 % confidence intervals (CI) for survival outcomes. Results: Sixteen studies reporting on 17 articles, which collectively included 457,256 patients. For the presence (CCI score ≥1) versus absence (CCI score of 0) of comorbidity, the pooled HR was 1.59 (95 % CI 1.43-1.77) for all-cause mortality, 0.98 (95 % CI 0.90-1.08) for PCa-specific mortality, and 1.88 (95 % CI 1.61-2.21) for other-cause mortality. When compared to a CCI score of 0, the pooled HR of all-cause mortality was 1.30 (95 % CI 1.18-1.44) for a CCI score of 1, 1.65 (95 % CI 1.37-2.00) for a CCI score ≥2, and 1.75 (95 % CI 1.57-1.95) for a CCI score ≥3. Additionally, the pooled HR of other cause mortality was 1.53 (95 % CI 1.41-1.67) for a CCI score of 1, 1.93 (95 % CI 1.74-2.75) for a CCI score ≥2, and 3.95 (95 % CI 2.13-7.34) for a CCI score ≥3. Conclusions: Increased comorbidity, as assessed by the CCI, significantly predicts all-cause and other-cause mortality in patients with PCa, but not PCa-specific mortality. The risk of all-cause and other-cause mortality increases with the burden of comorbidity.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma.

The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour-associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage-related clusters. We developed a M2 macrophage-related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single-cell sequencing data (GSE139324). We identified three distinct M2 macrophage-related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage-related genes significantly impact the development and progression of HNSC. The M2 macrophage-related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models.

BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

Traditional Banxia Xiexin decoction inhibits invasion, metastasis, and epithelial mesenchymal transition in gastric cancer by reducing lncRNA TUC338 expression.

Background: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine (TCM) formula clinically used to treat chronic gastritis, gastric ulcers, gastric cancer, and many other gastrointestinal diseases. Long noncoding RNAs (lncRNAs) have been shown to play an important role in maintaining the malignant phenotype of tumors. However, no relevant studies have shown whether Banxia Xiexin decoction regulates and controls lncRNA TUC338, and the effect of TUC338 on the regulation of gastric cancer invasion and metastasis remains unclear. Purpose: To investigate the ability of the traditional Chinese medicine (TCM) Banxia Xiexin decoction (BXD) to inhibit the migration and invasion of human gastric cancer AGS cells by regulating the long noncoding RNA (lncRNA) TUC338. Methods: UHPLC‒MS/MS was used to analyze the chemical components of BXD. MTT was performed to determine the effects of BXD on the proliferation of AGS cells. qRT‒PCR was used to determine the expression of lncRNA TUC338 in gastric cancer tissues, paracarcinoma tissues, AGS human gastric cancer cells and GES-1 normal gastric mucosa cells and to evaluate the effects of BXD on the expression of lncRNA TUC338 in AGS cells. Lentiviral transfection was used to establish human gastric cancer AGS cells with knocked down lncRNA TUC338 expression. The effects of lncRNA TUC338 knockdown on the migration and invasion of AGS cells were observed by a scratch assay and Transwell migration assay, respectively. Western blotting was performed to analyze the effects of lncRNA TUC338 knockdown on epithelial-to-mesenchymal transition (EMT) in AGS cells. We performed quality control on three batches of BXD. We used UHPLC‒MS/MS to control the quality of three random batches of BXD used throughout the study. Results: Ninety-five chemical components were identified from the water extract of BXD, some of which have anticancer effects. The expression of TUC.338 in gastric cancer tissues was higher than that in para-carcinoma tissues. BXD inhibited the invasion and migration of gastric cancer cells by inhibiting the expression of lncRNA TUC338, which reduced EMT. After knockdown of lncRNA TUC338, the migration and invasion of AGS cells were reduced; the expression of the EMT-related protein E-cadherin was increased, and the expression of N-cadherin and vimentin was reduced. Conclusions: The present results suggest that BXD has potential as an effective treatment for gastric cancer through the inhibition of lncRNA TUC338 expression.

The Potential Mechanism of Curcumin in Treating Oral Squamous Cell Carcinoma Based on Integrated Bioinformatic Analysis.

Aims: This study explores the effects of curcumin as a therapeutic agent against oral squamous cell carcinoma (OSCC). Methods: We acquired the targets of curcumin from three digital databases, including the Comparative Toxicogenomics Database, Search Tool for Interactions of Chemicals, and SwissTargetPrediction. Then, we identified the differentially expressed genes (DEGs) and the weighted gene coexpression network analysis-based key modules using the expression profiles of GSE23558 to acquire the OSCC-related genes. Additionally, the GeneCards and Online Mendelian Inheritance in Man databases were also used to identify the OSCC-related genes. Finally, curcumin-OSCC interaction genes were obtained by overlapping curcumin targets and OSCC-related genes. The enrichment analysis was performed by the ClusterProfiler algorithm and Metascape, respectively. Then, a protein-protein interaction network was created, and the maximal clique centrality algorithm was used to identify the top 10 hub genes. Besides, we examined the expression levels of hub genes in OSCC using The Cancer Genome Atlas database. Results: 927 DEGs were identified, including 308 upregulated ones and 619 downregulated ones. The cluster one-step network construction function of the WGCNA algorithm recognized a soft-thresholding power of 6, and 9083 genes were acquired. 2591 OSCC-related genes were obtained by overlapping the GSE23558-identified genes and the OSCC-related genes from disease target bases. Finally, we identified 70 candidate drug-disease interaction genes by overlapping the disease-related genes with the curcumin target. The enrichment analysis suggested that response to oxidative stress, epithelial cell proliferation, and AGE/RAGE pathway might involve in the effect of curcumin on OSCC. The topologic study identified the ten hub genes, including VEGFA, AKT1, TNF, HIF1A, EGFR, JUN, STAT3, MMP9, EGF, and MAPK3. A significant difference was observed in VEGFA, AKT1, TNF, HIF1A, EGFR, MMP9, EGF, and MAPK3 expression levels between head and neck squamous cell carcinoma and the normal controls. However, no significant difference was observed in JUN (P = 0.14) and STAT3 (P = 0.054). Conclusion: This study provided an overview and basis for the potential mechanism of curcumin against OSCC. The following experiments should be performed to further understand the effectiveness and safety of curcumin in treating OSCC.

Circ-ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages.

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.

SP2-induced circPUM1 modulates chemoresistance and nature killer cell toxicity in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.

Integrated models of blood protein and metabolite enhance the diagnostic accuracy for Non-Small Cell Lung Cancer.

BACKGROUND: For early screening and diagnosis of non-small cell lung cancer (NSCLC), a robust model based on plasma proteomics and metabolomics is required for accurate and accessible non-invasive detection. Here we aim to combine TMT-LC-MS/MS and machine-learning algorithms to establish models with high specificity and sensitivity, and summarize a generalized model building scheme. METHODS: TMT-LC-MS/MS was used to discover the differentially expressed proteins (DEPs) in the plasma of NSCLC patients. Plasma proteomics-guided metabolites were selected for clinical evaluation in 110 NSCLC patients who were going to receive therapies, 108 benign pulmonary diseases (BPD) patients, and 100 healthy controls (HC). The data were randomly split into training set and test set in a ratio of 80:20. Three supervised learning algorithms were applied to the training set for models fitting. The best performance models were evaluated with the test data set. RESULTS: Differential plasma proteomics and metabolic pathways analyses revealed that the majority of DEPs in NSCLC were enriched in the pathways of complement and coagulation cascades, cholesterol and bile acids metabolism. Moreover, 10 DEPs, 14 amino acids, 15 bile acids, as well as 6 classic tumor biomarkers in blood were quantified using clinically validated assays. Finally, we obtained a high-performance screening model using logistic regression algorithm with AUC of 0.96, sensitivity of 92%, and specificity of 89%, and a diagnostic model with AUC of 0.871, sensitivity of 86%, and specificity of 78%. In the test set, the screening model achieved accuracy of 90%, sensitivity of 91%, and specificity of 90%, and the diagnostic model achieved accuracy of 82%, sensitivity of 77%, and specificity of 86%. CONCLUSIONS: Integrated analysis of DEPs, amino acid, and bile acid features based on plasma proteomics-guided metabolite profiling, together with classical tumor biomarkers, provided a much more accurate detection model for screening and differential diagnosis of NSCLC. In addition, this new mathematical modeling based on plasma proteomics-guided metabolite profiling will be used for evaluation of therapeutic efficacy and long-term recurrence prediction of NSCLC.

Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Amine-Imine Nickel Catalysts with Pendant O-Donor Groups for Ethylene (Co)Polymerization.

The introduction of a secondary interaction is an efficient strategy to modulate transition-metal-catalyzed ethylene (co)polymerization. In this contribution, O-donor groups were suspended on amine-imine ligands to synthesize a series of nickel complexes. By adjusting the interaction between the nickel metal center and the O-donor group on the ligands, these nickel complexes exhibited high activities for ethylene polymerization (up to 3.48 × 106 gPE·molNi-1·h-1) with high molecular weight up to 5.59 × 105 g·mol-1 and produced good polyethylene elastomers (strain recovery (SR) = 69-81%). In addition, these nickel complexes can catalyze the copolymerization of ethylene with vinyl acetic acid, 6-chloro-1-hexene, 10-undecylenic, 10-undecenoic acid, and 10-undecylenic alcohol to prepare the functionalized polyolefins.

Hepatitis C virus nonstructural protein 4B induces lipogenesis via the Hippo pathway.

Hepatitis C virus (HCV) infection causes abnormal lipid metabolism in hepatocytes, which leads to hepatic steatosis and even hepatocellular carcinoma. HCV nonstructural protein 4B (NS4B) has been reported to induce lipogenesis, but the underlying mechanism is unclear. In this study, western blots were performed to investigate the effect of NS4B protein levels on key effectors of the Hippo and AKT signaling pathways. Yes-associated protein (YAP) and moesin-ezrin-radixin-like protein (Merlin) are effectors of the Hippo pathway. NS4B downregulated Merlin and phosphorylated YAP (p-YAP) protein expression while increasing the expression of the key AKT pathway proteins p-AKT and NF-κB. By observing the levels of AKT pathway proteins when Merlin was overexpressed or silenced, it was determined that Merlin mediates the AKT pathway. We suggest that HCV NS4B may mediate the AKT signaling pathway by inhibiting the Hippo pathway. Lipid droplets were observed in Huh7.5 cells overexpressing NS4B, and they increased significantly in number when Merlin was silenced. Overexpression of NS4B and Merlin silencing enhanced the expression of sterol regulatory element binding proteins (SREBPs), which have been demonstrated to be key regulatory factors controlling fatty acid synthesis. NS4B and Merlin silencing also enhanced the in vitro proliferative capacity of hepatocellular carcinoma cells. In conclusion, NS4B induces lipogenesis via the effect of the Hippo-YAP pathway on the AKT signaling pathway and thereby plays a significant role in the pathogenesis of HCV-associated diseases.

Polyphenolic-modified cellulose acetate membrane for bone regeneration through immunomodulation.

To enhance the bioactivity of cellulosic derivatives has become an important strategy to promote their value for clinical applications. Herein, protocatechualdehyde (PCA), a polyphenolic molecule, was used to modify a cellulose acetate (CA) membrane by combining with metal ions to confer an immunomodulatory activity. The PCA-modified CA membrane has shown a significant radical scavenging activity, thereby suppressed the inflammatory response and created a favorable immune microenvironment for osteogenesis and mineralization. Moreover, addition of metal ions could further stimulate the osteogenic differentiation of stem cells and accelerate bone regeneration both in vitro and in vivo. This study may provide a strategy to promote the immunomodulatory activity of cellulose-based biomaterials for bone regeneration.

Design of biopolymer-based hemostatic material: Starting from molecular structures and forms.

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application.