Carbonylative Cyclization of 2-Iodofluorobenzenes and 2-Aminophenols with Recyclable Palladium-Complexed Dendrimers on SBA-15: One-Pot Synthesis of Dibenzoxazepinones.

A novel, efficient, and practical route to dibenzoxazepinones has been developed through a one-pot heterogeneous palladium-catalyzed aminocarbonylation/aromatic nucleophilic substitution (SNAr) sequence starting from readily available 2-iodofluorobenzenes and 2-aminophenols. The carbonylative cyclization reaction proceeds smoothly in dimethyl sulfoxide (DMSO) at 120 °C with 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as the base by using a polyamidoamine (PAMAM)-dendronized SBA-15-supported bidentate phosphine-palladium complex [G(1)-2P-Pd(OAc)2-SBA-15] as the catalyst under 10 bar of CO, yielding a wide variety of dibenzo[b,e][1,4]oxazepin-11(5H)-one derivatives in good to excellent yields. Moreover, this new heterogenized dendritic palladium catalyst has competitive advantages in that it can be facilely recovered by simple filtration in air and recycled more than eight times without any significant loss of activity. The broad substrate scope, high functional group tolerance, and excellent palladium catalyst recyclability of the reaction make this approach a general, efficient, and economical method for the construction of valuable dibenzoxazepinone derivatives.

Establishment of an in Vitro Three-Dimensional Vascularized Micro-Tumor Model and Screening of Chemotherapeutic Drugs.

Breast cancer is the most common malignancy in women worldwide, and major challenges in its treatment include drug resistance and metastasis. Three-dimensional cell culture systems have received widespread attention in drug discovery studies but existing models have limitations, that warrant the development of a simple and repeatable three-dimensional culture model for high-throughput screening. In this study, we designed a simple, reproducible, and highly efficient microencapsulated device to co-culture MCF-7 cells and HUVECs in microcapsules to establish an in vitro vascularized micro-tumor model for chemotherapeutic drug screening. First, to construct a three-dimensional micro-tumor model, cell encapsulation devices were created using three different sizes of flat-mouthed needles. Immunohistochemistry and immunofluorescence assays were conducted to determine vascular lumen formation. Cell proliferation was detected using the Cell Counting Kit-8 assay. Finally, to observe the drug reactions between the models, anticancer drugs (doxorubicin or paclitaxel) were added 12 h after the two-dimensional cultured cells were plated or 7 days after cell growth in the core-shell microcapsules. Vascularized micro-tumors were obtained after 14 days of three-dimensional culture. The proliferation rate in the three-dimensional cultured cells was slower than that of two-dimensional cultured cells. Three-dimensional cultured cells were more resistant to anticancer drugs than two-dimensional cultured cells. This novel sample encapsulation device formed core-shell microcapsules and can be used to successfully construct 3D vascularized micro-tumors in vitro. The three-dimensional culture model may provide a platform for drug screening and is valuable for studying tumor development and angiogenesis.

Causality of blood metabolites and metabolic pathways on peripheral arteriosclerosis: a Mendelian randomization study.

Background: Peripheral arteriosclerosis is caused by any atherosclerosis outside the heart and brain. However, the underlying biological mechanisms are not fully understood. This study aims to explore the causal relationship between blood metabolites and peripheral arteriosclerosis. Methods: A Mendelian randomization (MR) analysis was implemented to estimate the causality of blood metabolites on peripheral arteriosclerosis. A genome-wide association study (GWAS) of 1,400 metabolites was used as the exposure, whereas two different GWAS datasets of peripheral arteriosclerosis were the outcomes. Inverse-variance weighted (IVW) was the main analysis of causal analysis. MR-Egger, the simple mode, weighted median and weighted mode were used to increase the stability and robustness of the results. Cochran Q test, MR-Egger intercept test, the funnel plot, and MR-Pleiotropy RESidual Sum and Outlier were used for sensitivity analyses. Furthermore, metabolic pathway enrichment analysis was performed using MetaboAnalyst5.0. Results: In this MR study, eight blood metabolites have a strong causal relationship with peripheral arteriosclerosis, including 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4), 1-palmitoyl-2-arachidonoyl-gpc (16:0/20:4n6), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE, 1-palmitoyl-2-dihomo-linolenoyl-GPC, Gamma-glutamylleucine, Deoxycholic acid glucuronide and two named X- (X-24546, X-26111). In addition, five important metabolic pathways in peripheral arteriosclerosis were identified through metabolic pathway analysis. Conclusion: This study provides evidence for the causal relationship between blood metabolites and peripheral arteriosclerosis, and these eight blood metabolites provide new perspectives for screening and prevention of peripheral arteriosclerosis in the future.

Life cycle environmental impacts of urban water systems in China.

Urban water systems in China are facing multiple challenges, including rapid urbanisation, climate change and infrastructure ageing. It is crucial to evaluate their environmental performance from a holistic perspective in planning and management processes. To the best of our knowledge, there is a lack of nationwide life cycle assessment (LCA) studies on China's urban water systems that cover all system stages. Therefore, this study aims to present a comprehensive and nationwide LCA analysis that pinpoints the environmental hotspots and their major sources across China. This study was conducted based on water utility databases at the province level, covering water abstraction and treatment, waterwork sludge treatment, water distribution, sewage collection, stormwater drainage, wastewater treatment and sewage sludge treatment. Nine environmental impact categories were calculated and analysed. The results reveal the inequity of environmental impacts across provinces, with overall impacts geographically higher in the east and south, lower in the west and north. However, at the functional unit level, the impacts in the northern and northeastern provinces are higher than other regions. Most environmental categories are dominated by multiple water system stages. The analyses of underlying drivers found that purchased electricity is the primary source of several environmental impacts. This study provides a holistic understanding of the environmental performance of China's urban water systems, offers some insights for comprehensive decision-making support on sustainable water system management, and can also serve as a benchmark for future scenario analysis to explore options for reducing environmental impact.

Integrated analysis to identify biological features and molecular markers of poorly cohesive gastric carcinoma (PCC).

As one of the two main histologic subtypes of gastric cancer (GC), diffuse-type gastric cancer (DGC) containing poorly cohesive gastric carcinoma (PCC) components has a worse prognosis and does not respond well to typical therapies. Despite the large number of studies revealing the complex pathogenic network of DGC, the molecular heterogeneity of DGC is still not fully understood. We obtained single-cell RNA-seq data and bulk data from the tumor immune single cell hub, the public gene expression omnibus, and the cancer genome atlas databases. A series of bioinformatics analyses were performed using R software. Immunofluorescence staining, hematoxylin and eosin staining, western blot, and functional experiments were used for experimental validation. Caudin-3, -4 and -7 were lowly expressed in DGC and their expression levels were further reduced in PCC. The PCC components were mainly located in the deeper layers of the DGC and had a high level of hypoxic Wnt/ß-catenin signaling and stemness. We further identified Insulin Like Growth Factor Binding Protein 7 (IGFBP7) as a marker for PCC components in the deep layer. IGFBP7 is stimulated by hypoxia and promotes cancer cell invasiveness and reduced claudin expression. In addition, programmed death-1 ligand (PD-L1) was specifically expressed in the deep layer, reflecting deep layer-specific immunosuppression. The PCC components are predominantly situated in the deeper layers of DGC. Initial molecular characterization of these PCC components revealed distinct features, including low expression of claudin-3, -4, and -7, high expression of IGFBP7, and the presence of PD-L1. These molecular traits may partially account for the pronounced tumor heterogeneity observed in GC.

Adipose-derived mesenchymal stem cells suppress fibroblast proliferation of hypertrophic scar through CCL5 and CXCL12.

BACKGROUND AND OBJECTIVE: Adipose-derived mesenchymal stem cells (ADSCs) can accelerate wound healing, reduce scar formation, and inhibit hypertrophic scar (HTS). ADSCs can secrete a large amount of CCL5, and CCL5 has been proved to be pro-inflammatory and pro-fibrotic. CXCL12 (SDF-1) is a key chemokine that promotes stem cell migration and survival. Therefore, this study selected normal skin and HTS conditioned medium to simulate different microenvironments, and analyzed the effects of different microenvironments on the expression of CCL5 and CXCL12 in human ADSCs (hADSCs). MATERIALS AND METHODS: hADSCs with silenced expression of CCL5 and CXCL12 were co-cultured with hypertrophic scar fibroblasts to verify the effects of CCL5 and CXCL12 in hADSCs on the proliferation ability of hypertrophic scar fibroblasts. A mouse model of hypertrophic scar was established to further confirm the effect of CCL5 and CXCL12 in hADSCs on hypertrophic scar formation. RESULTS: CCL5 level was found to be significantly high in hADSCs cultured in HTS conditioned medium. CXCL12 in HTS group was prominently lowly expressed compared with the normal group. Inhibition of CCL5 in hADSCs enhanced the effects of untreated hADSCs on proliferation of HTS fibroblasts while CXCL12 knockdown exerted the opposite function. Inhibition of CCL5 in hADSCs increased the percentage of HTS fibroblasts in the G0/G1 phase while down-regulation of CXCL12 decreased those. Meanwhile, the down-regulated levels of fibroblast markers including collagen I, collagen III, and α-SMA induced by CCL5 knockdown were significantly up-regulated by CXCL12 inhibition. hADSCs alleviate the HTS of mice through CCL5 and CXCL12. CONCLUSION: In summary, our results demonstrated that hADSCs efficiently cured HTS by suppressing proliferation of HTS fibroblasts, which may be related to the inhibition of CXCL12 and elevation of CCL5 in hADSCs, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of HTS.

ROCK2 increases drug resistance in acute myeloid leukemia via metabolic reprogramming and MAPK/PI3K/AKT signaling.

Rho-associated coiled-coil kinase 2 (ROCK2) is classified as a member of the serine/threonine protein kinase family and has been identified as a key driver of the development of various forms of cancer. The cause of ROCK2's impact on acute myeloid leukemia (AML) is still unknown. We found that ROCK2 expression was higher in AML patients, leading to lower complete response rates and worse overall survival. Additionally, ROCK2 expression was elevated in the doxorubicin-resistant leukemia cell line HL-60/ADM when compared to their individual parent cells. Moreover, the suppression or inhibition of ROCK2 leads to enhanced drug sensitivity in both AML cell lines and primary AML specimens, along with a notable decrease in downstream signaling pathways. Furthermore, the suppression of ROCK2 caused disruption of cellular energy production pathways by directly affecting the functionality of proteins within the mitochondrial electron transport chain. Finally, we discovered that TRIM26, a specific E3 ligase, is capable of ubiquitylating ROCK2, and the upregulation of TRIM26 within HL-60/ADM cells resulted in heightened sensitivity to the drug and reduced resistance. Thus, our study presents a new strategy for overcoming drug resistance in AML through targeting ROCK2/AKT/MAPK signaling pathway.

Cyy-272, an indazole derivative, effectively mitigates obese cardiomyopathy as a JNK inhibitor.

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

Depressive and anxiety symptoms in caregivers of children with congenital ectopia lentis: a prospective cross-sectional study.

OBJECTIVES: To evaluate the frequency and severity of depressive and anxiety symptoms and explore possible risk factors among caregivers of children with congenital ectopia lentis (CEL). DESIGN: A prospective cross-sectional study was conducted. PARTICIPANTS: 108 patients and 108 informal caregivers (mainly parents) were included. Participants were grouped based on whether patients had systemic abnormalities: group 1 were children without systemic abnormalities and group 2 were children with systemic abnormalities. OUTCOME MEASURES: The 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) were used to assess depressive and anxiety symptoms, respectively. RESULTS: More than half of caregivers (51.9%) have depressive or anxiety symptoms of some degree. 38.0% of caregivers suffered from both depressive and anxiety symptoms. 19.4% of caregivers had moderate to severe depressive symptoms (PHQ-9 score ≥10) while 16.7% reported moderate to severe anxiety symptoms (GAD-7 score ≥10). Between the two groups, the mean PHQ-9 and GAD-7 scores significantly differed (p=0.026 in PHQ-9; p=0.018 in GAD-7). The proportion of caregivers with moderate to severe symptoms was greater in group 2 than in group 1. In addition, there was a significant positive correlation between PHQ-9 and GAD-7 scores (r=0.827; p<0.001). Furthermore, best corrected visual acuity in the better eye of patients was positively correlated with both the PHQ-9 and GAD-7 scores (r=0.314, p<0.05 in PHQ-9; r=0.325, p<0.05 in GAD-7). CONCLUSIONS: Depressive and anxiety symptoms were common in caregivers of children with CEL, especially among those whose children had other systemic disease manifestations or low vision. This study illustrates the importance of depressive and anxiety symptom screening for these caregivers to implement effective psychological interventions and support strategies.

MiR-338-5p, a novel metastasis-related miRNA, inhibits triple-negative breast cancer progression by targeting the ETS1/NOTCH1 axis.

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

EBF1-COX4I2 signaling axis promotes a myofibroblast-like phenotype in cancer-associated fibroblasts (CAFs) and is associated with an immunosuppressive microenvironment.

Immunotherapy has limited response rates in colorectal cancer (CRC) due to an immunosuppressive tumor microenvironment (TME). Combining transcriptome sequencing, clinical specimens, and functional experiments, we identified a unique group of CAF subpopulations (COX4I2 + ) with inhibited mitochondrial respiration and enhanced glycolysis. Through bioinformatics predictions and luciferase reporter assays, we determined that EBF1 can upstreamly regulate COX4I2 transcription. COX4I2 + CAFs functionally and phenotypically resemble myofibroblasts, are important for the formation of the fibrotic TME, and are capable of activating the M2 phenotype of macrophages. In vitro experiments demonstrated that COX4I2 + CAFs promote immunosuppressive TME by blocking CD8 + T cell infiltration and inducing CD8 + T cell dysfunction. Using multiple independent cohorts, we also found a strong correlation between the immunotherapy response rate of CRC patients and COX4I2 expression in their tumors. Our results identify a CAF subpopulation characterized by activation of the EBF1-COX4I2 axis, and this group of CAFs can be targeted to improve cancer immunotherapy outcomes.

Rational design of a highly effective cellulose-based macromolecular fluorescent probe for real-time recognition of palladium ion in environmental samples and its applications in plant and zebrafish.

Palladium ion (Pd2+) plays an important role in our daily life, but poses a great threat to the environment and human health. Thus, it is desirable to exploit a rapid and sensitive approach to realize the detection of Pd2+. In this study, a cellulose acetate-based macromolecular fluorescent probe CA-NA-PA was successfully prepared for tracking amounts of Pd2+. CA-NA-PA showed an obvious "on-off" fluorescence response to Pd2+, accompanied by the fluorescence color changed from bright yellow to colorless. CA-NA-PA had some outstanding detection performances such as low detection limit (26 nM), extremely short response time (1 min), good selectivity and anti-interference ability. Based on the advantages of probe mentioned above, CA-NA-PA could realize recognition of Pd2+ concentration in environmental water and soil samples. What's more, the probe CA-NA-PA was applied to image Pd2+ in zebrafish as well as in live onion tissue due to the good biocompatibility and cell membrane permeability of cellulose, suggesting its wide application prospect in biosystems.

A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice.

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.

Machine learning-based prediction model of lower extremity deep vein thrombosis after stroke.

This study aimed to apply machine learning (ML) techniques to develop and validate a risk prediction model for post-stroke lower extremity deep vein thrombosis (DVT) based on patients' limb function, activities of daily living (ADL), clinical laboratory indicators, and DVT preventive measures. We retrospectively analyzed 620 stroke patients. Eight ML models-logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), neural network (NN), extreme gradient boosting (XGBoost), Bayesian (NB), and K-nearest neighbor (KNN)-were used to build the model. These models were extensively evaluated using ROC curves, AUC, PR curves, PRAUC, accuracy, sensitivity, specificity, and clinical decision curves (DCA). Shapley's additive explanation (SHAP) was used to determine feature importance. Finally, based on the optimal ML algorithm, different functional feature set models were compared with the Padua scale to select the best feature set model. Our results indicated that the RF algorithm demonstrated superior performance in various evaluation metrics, including AUC (0.74/0.73), PRAUC (0.58/0.58), accuracy (0.75/0.77), and sensitivity (0.78/0.80) in both the training set and test set. DCA analysis revealed that the RF model had the highest clinical net benefit. SHAP analysis showed that D-dimer had the most significant influence on DVT, followed by age, Brunnstrom stage (lower limb), prothrombin time (PT), and mobility ability. The RF algorithm can predict post-stroke DVT to guide clinical practice.

Bilateral Embedded Anchoring via Tailored Polymer Brush for Large-Area Air-processed Blue Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

Dynamic Directional Ultrasonically In Situ-Generated N,S-Codoped Carbon Dots in Poly(ethylene glycol) for Improved Tribological Performance.

The dispersion stability of nanomaterials in lubricants significantly influences tribological performance, yet their addition as lubricant additives often presents challenges in secondary dispersion. Here, we present a straightforward method for in situ preparation of N,S-codoped CDs (N,S-CDs)-based lubricants using heterocyclic aromatic hydrocarbons containing N/S elements in poly(ethylene glycol) (PEG) base oil by a directional ultrasound strategy. Two types of N,S-CDs were successfully prepared via the directional ultrasound treatment of PEG with benzothiazole (BTA) and benzothiadiazole (BTH) separately. The resultant N,S-CDs have a uniform distribution of N and S elements and maintain good colloidal dispersion stability in PEG even after 9 months of storage. The N,S-CDs can enter the surface gap of the friction pairs and then induce a tribochemical reaction. Benefiting from the synergistic effect of N and S activating elements, a robust and stable protective film consisting of iron sulfides, iron oxides, carbon nitrides, and amorphous carbonaceous compounds is formed, thus endowing N,S-CDs-based lubricants with improved antiwear and friction-reducing performance. Compared with pure PEG, the coefficient of friction (COF) of the N,S-CDs(BTH)-based lubricant decreased to 0.108 from 0.292, accompanied by a 91.2% reduction in wear volume, and the maximum load carrying capacity increased to 450 from 150 N.

Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity.

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.

Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer.

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.

Fabrication of Poly(ionic liquid) Hydrogels Incorporating Liquid Metal Microgels for Enhanced Synergistic Antifouling Applications.

Hydrogels are ideal for antifouling materials due to their high hydrophilicity and low adhesion properties. Herein, poly(ionic liquid) hydrogels integrated with zwitterionic copolymer-functionalized gallium-based liquid metal (PMPC-GLM) microgels were successfully prepared by a one-pot reaction. Poly(ionic liquid) hydrogels (IL-Gel) were obtained by chemical cross-linking the copolymer of ionic liquid, acrylic acid, and acrylamide, and the introduction of ionic liquid (IL) significantly increased the cross-linking density; this approach consequently enhanced the mechanical and antiswelling properties of the hydrogels. The swelling ratio of IL-Gel decreased eight times compared to the original hydrogels. PMPC-GLM microgels were prepared through grafting the zwitterionic polymer PMPC onto the GLM nanodroplet surface, which exhibited efficient antifouling performance attributed to the bactericidal effect of Ga3+ and the antibacterial effect of the zwitterionic polymer layer PMPC. Based on the synergistic effect of PMPC-GLM microgels and IL, the composite hydrogels PMPC-GLM@IL-Gel not only exhibited excellent mechanical and antiswelling properties but also showed outstanding antibacterial and antifouling properties. Consequently, PMPC-GLM@IL-Gel hydrogels achieved inhibition rates of over 90% against bacteria and more than 85% against microalgae.