Single-cell analyzing of tumor microenvironment and cell adhesion between early and late-stage lung cancer.

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that threaten human life with serious incidence and high mortality. High heterogeneity of tumor microenvironment (TME) was reported in multiple studies. However, the factor of controlling the tumor migration progression between eary and late-stage LUAD is still not fully understood. In this study, we conducted a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data of LUAD obtained from the GEO database. The identification of cell clusters revealed significant expansion of epithelial cells in late-stage patients. Interpretation of the cell-cell communication results between early-stage and late-stage patient samples indicated that early tumor cells may interact with epithelial cells through the TGF-ß pathway to promote tumor progression. The cell cycle analysis demonstrated a significant increase in the number of cells in the G2 and M phases in late-stage lung cancer. Further analysis using Non-negative Matrix Factorization (NMF) revealed early-stage cell-specific gene features involved in cell adhesion-related biological processes. Among these, the Tensin (TNS) gene family, particularly TNS1, showed high expression in epithelial cells and fibroblasts of early-stage samples, specifically associated with cell adhesion. Survival analysis using TCGA database for LUAD demonstrated that patients with high expression of TNS1 exhibited significantly higher overall survival rates compared to those with low expression. Immunofluorescence experiments have demonstrated co-expression of TNS1 with fibroblast and tumor cell markers (α-SMA and EPCAM). Immunohistochemistry experiments further validated the significantly higher expression levels of TNS1 in early-stage LUAD tissues compared to late-stage lung cancer tissues (P<0.05). Pathway experiments have shown that early-stage tumor patients with high expression of TNS1 exhibit stronger phosphorylation levels of Akt and mTOR, indicating a more potent activation of the Akt/mTOR signaling pathway. In conclusion, the results of this study demonstrate that TNS1 is an adhesive molecule in the immune microenvironment of early-stage tumor cells, and it may serve as a novel prognostic marker for lug cancer.

Efficacy of cross-line anti-programmed death 1/programmed cell death-ligand 1 antibody in the treatment of advanced nonsmall cell lung cancer: A retrospective study.

Background and Aims: Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross-line ICIs therapy is effective in treating non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results: Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross-line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross-line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061-30.979), 31.643 (95% CI: 23.513-39.774), and 7.997 (95% CI: 3.746-12.247) months, respectively (p = 0.003). The median second progression-free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276-5.864), 3.530 (95% CI: 0.674-6.386), and 1.570 (95% CI: 0-4.091) months, respectively (p = 0.091). Conclusions: Cross-line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

Cancer progression and tumor hypercoagulability: a platelet perspective.

Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Causal effects of immune cells in glioblastoma: a Bayesian Mendelian Randomization study.

Background: Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined. Method: In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis. Results: After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515-0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L- HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004-2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031-1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma. Conclusion: Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

Enhanced Nanotwinned Copper Bonding through Epoxy-Induced Copper Surface Modification.

For decades, Moore's Law has neared its limits, posing significant challenges to further scaling it down. A promising avenue for extending Moore's Law lies in three-dimensional integrated circuits (3D ICs), wherein multiple interconnected device layers are vertically bonded using Cu-Cu bonding. The primary bonding mechanism involves Cu solid diffusion bonding. However, the atomic diffusion rate is notably low at temperatures below 300 °C, maintaining a clear and distinct weak bonding interface, which, in turn, gives rise to reliability issues. In this study, a new method of surface modification using epoxy resin to form fine grains on a nanotwinned Cu film was proposed. When bonded at 250 °C, the interfacial grains grew significantly into both sides of the Cu film. When bonded at 300 °C, the interfacial grains extended extensively, eventually eliminating the original bonding interface.

Identification and Verification of a Glycolysis-Related lncRNA Prognostic Signature for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. The search for a new biomarker could help the prognosis of HCC patients. We identified the glycolytic gene set associated with HCC and the glycolytic lncRNA based on TCGA and MsigDB databases. According to these lncRNAs, K-means clustering, and regression analysis were performed on the patients. Two groups of HCC patients with different lncRNA expression levels were obtained based on K-means clustering results. The results of difference analysis and enrichment analysis showed that DEmRNA in the two HCC populations with significant survival differences was mainly enriched in transmembrane transporter complex, RNA polymerase II specificity, cAMP signaling pathway, and calcium signaling pathway. In addition, a prognostic model of HCC with 4 DElncRNAs was constructed based on regression analysis. ROC curve analysis showed that the model had good predictive performance. Drug predictionresults showed that the efficacy of JQ1, niraparib, and teniposide was higher in the low-risk group than in the high-risk group. In conclusion, this study preliminarily identified glycolytic-related prognostic features of lncRNAs in HCC and constructed a risk assessment model. The results of this study are expected to guide the prognosis assessment of clinical HCC patients.

Low Bone Mineral Density as a Predictor of Mortality and Infections in Stroke Patients: A Hospital-based Study.

CONTEXT: Low bone mineral density (BMD) has been linked to elevated risks of mortality and infections in the general population; however, its association with these outcomes in stroke patients remains unclear. OBJECTIVE: This study aims to investigate the correlation between low BMD and risks of mortality and infections among stroke patients in a Taiwanese cohort. METHODS: In this single-centered retrospective cohort study, 905 stroke patients from a Taiwanese database (2000-2022) were analyzed. Patients were divided based on BMD measurements of the femur and spine. The primary outcome was all-cause mortality, and secondary outcomes included urinary tract infection (UTI) and pneumonia. Accelerated failure time regression model analyses evaluated the association between BMD and these outcomes, while the Kaplan-Meier method and log-rank test assessed survival differences between groups. RESULTS: Among the participants (average age 76.1 years, 70.5% female), 33.82% had osteopenia and 55.25% had osteoporosis. Stroke patients with lower spine and right femur BMD had significantly reduced survival rates, especially when the BMD value fell below 0.842 g/cm2 (spine), and 0.624 g/cm2 (right femur), respectively. Regarding secondary outcomes, lower spine BMD was significantly associated with an increased risk of UTI. CONCLUSION: Low BMD, particularly in the femur and spine, is a significant predictor of mortality and UTI in stroke patients. These findings highlight the importance of assessing and managing BMD in stroke patients to improve outcomes and reduce complications.

Single Molecular Nanomedicines Based on Macrocyclic Carrier-Drug Conjugates for Concentration-Independent Encapsulation and Precise Activation of Drugs.

Nanomedicines often rely on noncovalent self-assembly and encapsulation for drug loading and delivery. However, challenges such as reproducibility issues due to the multicomponent nature, off-target activation caused by premature drug release, and complex pharmacokinetics arising from assembly dissociation have hindered their clinical translation. In this study, we introduce an innovative design concept termed single molecular nanomedicine (SMNM) based on macrocyclic carrier-drug conjugates. Through the covalent linkage of two chemotherapy drugs to a hypoxia-cleavable macrocyclic carrier, azocalix[4]arene, we obtained two self-included complexes to serve as SMNMs. The intramolecular inclusion feature of the SMNMs has not only demonstrated comprehensive shielding and protection for the drugs but also effectively prevented off-target drug leakage, thereby significantly reducing their side effects and enhancing their antitumor therapeutic efficacy. Additionally, the attributes of being a single component and molecularly dispersed confer advantages such as ease of preparation and good reproducibility for SMNMs, which is desirable for clinical applications.

Construction of Dual-Active Sites by Interfacing with Polyhydroxy Fullerene on Nickel Hydroxide Surfaces to Promote CO2 Deep Photoreduction to CH4.

Due to the complex series of elementary steps involved, achieving deep photoreduction of CO2 to multielectron products such as CH4 remains a challenging task. Therefore, it is crucial to strategically design catalysts that facilitate the controlled formation of the crucial intermediates and provide precise control over the reaction pathway. Herein, we present a pioneering approach by employing polyhydroxy fullerene (PHF) molecules to modify the surface of Ni(OH)2, creating stable and effective synergistic sites to enhance the formation of CH4 from CO2 under light irradiation. As a result, the optimized PHF-modified Ni(OH)2 cocatalyst achieves a CH4 production rate of 455 µmol g-1 h-1, with an electron-based selectivity of approximately 60%. The combination of in situ characterizations and theoretical calculations reveals that the hydroxyl species on the surface of PHF can participate in stabilizing crucial intermediates and facilitating water activation, thereby altering the reaction pathway to form CH4 instead of CO. This study provides a novel approach to regulating the selectivity of photocatalytic CO2 reduction by exploring molecular surface modification through interfacing with functionalized carbon clusters.

Comparative Analysis of the Anti-Inflammatory Effects of Liraglutide and Dulaglutide.

Inflammation plays a pathophysiological role in atherosclerosis and its clinical consequences. In addition to glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are of wide concern for cardioprotective effects. The structure, half-life, homology, and clinical efficacy of GLP-1RAs exhibit remarkable disparity. Several studies have compared the disparities in anti-inflammatory effects between daily and weekly GLP-1RAs. This study aimed to compare the similarities and differences between liraglutide and dulaglutide in terms of inhibiting atherosclerotic inflammation and improving co-cultured endothelial cell function. The expression of inflammation markers was examined by immunofluorescence, Western blotting, and real-time PCR. The tube-forming ability of endothelial cells was tested on Matrigel. The results verify that 10/50/100 nmol/L liraglutide and 100 nmol/L dulaglutide markedly suppressed the expression of inflammatory factors in LPS-induced atherosclerosis after 24 and 72 hours, respectively. Moreover, they promoted the polarization of M1 macrophages toward the M2 phenotype and improved the function of co-cultured endothelial cells. Both liraglutide and dulaglutide ameliorate atherosclerosis development. The difference between the two resided in the extended intervention duration required to observe the effect of dulaglutide, and liraglutide demonstrated a superior dose-dependent manner. We provide a potential strategy to understand the dynamics of drug action and possible timing administration.

Enhanced sensitivity of extracellular antibiotic resistance genes (ARGs) to environmental concentrations of antibiotic.

As emerging contaminants, antibiotics are frequently present in various environments, particularly rivers, albeit often at sublethal concentrations (ng/L∼µg/L). Assessing the risk associated with these low levels, which are far below the lethal threshold for most organisms, remains challenging. In this study, using microcosms containing planktonic bacteria and biofilm, we examined how antibiotic resistance genes (ARGs) in different physical states, including intracellular ARGs (iARGs) and extracellular ARGs (eARGs) responded to these low-level antibiotics. Our findings reveal a positive correlation between sub-lethal antibiotic exposure (ranging from 0.1 to 10 µg/L) and increased prevalence (measured as ARG copies/16s rDNA) of both iARGs and eARGs in planktonic bacteria. Notably, eARGs demonstrated greater sensitivity to antibiotic exposure compared to iARGs, with a lower threshold (0.1 µg/L for eARGs versus 1 µg/L for iARGs) for abundance increase. Moreover, ARGs in biofilms demonstrates higher sensitivity to antibiotic exposure compared to planktonic bacteria. To elucidate the underlying mechanisms, we established an integrated population dynamics-pharmacokinetics-pharmacodynamics (PD-PP) model. This model indicates that the enhanced sensitivity of eARGs is primarily driven by an increased potential for plasmid release from cells under low antibiotic concentrations. Furthermore, the accumulation of antibiotic in biofilms induces a greater sensitivity of ARG compared to the planktonic bacteria. This study provides a fresh perspective on the development of antibiotic resistance and offers an innovative approach for assessing the risk of sublethal antibiotic in the environment.

Risk Factors and Clinical Significance of Ultra-Long-Term Microischemia After Intracranial Aneurysm Embolization.

INTRODUCTION: This study aimed to explore influencing factors and clinical significance of ultra-long-term microischemia following intracranial aneurysm (IA) embolization and establish a theoretical foundation for reducing both the incidence of ultra-long-term microischemia and cognitive dysfunction in patients post embolization. METHODS: A retrospective analysis was conducted on data from 147 patients who received endovascular treatment for IAs. Patients were categorized into microischemic and control (non-microischemic) groups on the based on the findings of high-resolution magnetic resonance vessel wall imaging (HR-VWI) examinations performed 3 days postoperatively and 6 months postoperatively. Risk factors for the occurrence of ultra-long-term microischemia were determined by univariate analysis and multivariate logistic regression analysis. RESULTS: Out of 147 patients included in the study, 51 (34.69%) developed microischemia while the remaining 96 (65.31%) did not experience this condition. Analysis revealed that factors such as sex, age, history of underlying diseases (hypertension, diabetes mellitus), aneurysmal site characteristics, the presence or absence of stenosis in the aneurysm-bearing artery, modified Fisher score at admission, Barthel's index at discharge, immunoinflammatory index at 3 days postoperatively and at the 6-month follow-up, the presence or absence of aneurysmal wall enhancement, and the presence or absence of aneurysmal lumen showed no statistically significant differences between the two groups (all P > 0.05). By contrast, variables like in operative time, rupture status of the aneurysm before surgery according to World Federation of Neurologic Surgeons (WFNS) grade, aneurysm size, number of stents used, number of guidewires and catheters used, and Evans index between the two groups were found to have statistically significant disparities between those who developed microischemia and those who did not (P < 0.05). A subsequent multivariate analysis revealed that aneurysm size, Evans index, and the number of stents used were independent risk factors for the occurrence of ultra-long-term microischemia after surgical intervention of aneurysms (P < 0.05). The receiver operating characteristic (ROC) curves of the patients were constructed on the basis of risk factors determined through multivariate logistic regression analysis. Results indicated that aneurysm size (area under ROC curve (AUC) 0.619, sensitivity 94.7%, specificity 17.1%, P = 0.049), Evans index (AUC 0.670, sensitivity 96.4%, specificity 26.8%, P = 0.004), and number of stents (AUC 0.639, sensitivity 44.6%, specificity 90.2%, P < 0.001) effectively predicted the occurrence of microischemia. The incidence of cognitive dysfunction was higher in the microischemic group than in the control group (P < 0.05), and a greater number of microischemic foci was associated with a higher incidence of cognitive dysfunction. The proportion of microschemia foci in the thalamus and basal ganglia in patients with cognitive dysfunction (60.87%) was significantly higher than that in patients without cognitive dysfunction (34.55%) (P < 0.05). CONCLUSION: Aneurysm size, Evans index > 0.3, and the quantity of stents were independent risk factors for the occurrence of ultra-long-term microischemia after aneurysm embolization and provided good predictive performance. Cognitive dysfunction was closely associated with microischemia, with its severity increasing with an increase in the number of ischemic foci.

Effect of metabolic dysfunction on the risk of liver-related events in patients cured of hepatitis C virus.

The impact of metabolic dysfunction or metabolic dysfunction-associated fatty liver disease (MAFLD) on liver-related events (LREs) in patients with chronic hepatitis C (CHC) who had achieved a sustained virologic response (SVR) to direct-acting antiviral agents (DAAs) is unknown. A total of 924 patients with cured CHC and documented body mass index (BMI) were included in the analysis, and the data period was from September 2012 to April 2022. Hepatic steatosis was identified either through ultrasonography or blood biomarkers. Metabolic dysfunction was defined as the presence of overweight or obesity (BMI ≥ 23 kg/m2), type 2 diabetes mellitus (DM), and metabolic dysregulation. Patients may have more than one metabolic dysfunction. Variables at 12 or 24 weeks after DAA therapy (PW12) were used to identify predictors of LREs. The median age of the 924 patients was 58 (49-65) years. Of the participants, 418 (45.2%) were male. The median BMI was 24.01 (21.78-26.73) kg/m2, and 174 (18.8%) patients had DM. A multivariable Cox regression analysis revealed that age, male, albumin, total bilirubin, alpha-fetoprotein (AFP), metabolic dysfunction (hazard ratio: 1.709, 95% confidence interval: 1.128-2.591, P = .011), and FIB-4 > 3.25 were independent predictors of LREs. Type 2 DM and metabolic dysregulation exhibited a larger time-dependent area under the receiver operating characteristic curve for LREs than did overweight or obesity. Moreover, metabolic dysfunction was identified to be an independent predictor of hepatocellular carcinoma. Metabolic dysfunction increased the risk of LREs and HCC in patients with CHC who had achieved an SVR to DAA therapy.

Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage.

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1ß, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.

Enhanced Copper Bonding Interfaces by Quenching to Form Wrinkled Surfaces.

For decades, Moore's Law has been approaching its limits, posing a huge challenge for further downsizing to nanometer dimensions. A promising avenue to replace Moore's Law lies in three-dimensional integrated circuits, where Cu-Cu bonding plays a critical role. However, the atomic diffusion rate is notably low at temperatures below 300 °C, resulting in a distinct weak bonding interface, which leads to reliability issues. In this study, a quenching treatment of the Cu film surface was investigated. During the quenching treatment, strain energy was induced due to the variation in thermal expansion coefficients between the Si substrate and the Cu film, resulting in a wrinkled surface morphology on the Cu film. Grain growth was observed at the Cu-Cu bonding interface following bonding at 300 °C for 2 and 4 h. Remarkably, these procedures effectively eliminated the bonding interface.

Sulfonated Azocalix[4]arene-Modified Metal-Organic Framework Nanosheets for Doxorubicin Removal from Serum.

Chemotherapy is one of the most commonly used methods for treating cancer, but its side effects severely limit its application and impair treatment effectiveness. Removing off-target chemotherapy drugs from the serum promptly through adsorption is the most direct approach to minimize their side effects. In this study, we synthesized a series of adsorption materials to remove the chemotherapy drug doxorubicin by modifying MOF nanosheets with sulfonated azocalix[4]arenes. The strong affinity of sulfonated azocalix[4]arenes for doxorubicin results in high adsorption strength (Langmuir adsorption constant = 2.45-5.73 L mg-1) and more complete removal of the drug. The extensive external surface area of the 2D nanosheets facilitates the exposure of a large number of accessible adsorption sites, which capture DOX molecules without internal diffusion, leading to a high adsorption rate (pseudo-second-order rate constant = 0.0058-0.0065 g mg-1 min-1). These adsorbents perform effectively in physiological environments and exhibit low cytotoxicity and good hemocompatibility. These features make them suitable for removing doxorubicin from serum during "drug capture" procedures. The optimal adsorbent can remove 91% of the clinical concentration of doxorubicin within 5 min.

GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction.

BACKGROUND: A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types. METHODS: In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database. RESULT: Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells. CONCLUSION: Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.

Autophagy receptor ZmNBR1 promotes the autophagic degradation of ZmBRI1a and enhances drought tolerance in maize.

Drought stress is a crucial environmental factor that limits plant growth, development, and productivity. Autophagy of misfolded proteins can help alleviate the damage caused in plants experiencing drought. However, the mechanism of autophagy-mediated drought tolerance in plants remains largely unknown. Here, we cloned the gene for a maize (Zea mays) selective autophagy receptor, NEXT TO BRCA1 GENE 1 (ZmNBR1), and identified its role in the response to drought stress. We observed that drought stress increased the accumulation of autophagosomes. RNA sequencing and reverse transcription-quantitative polymerase chain reaction showed that ZmNBR1 is markedly induced by drought stress. ZmNBR1 overexpression enhanced drought tolerance, while its knockdown reduced drought tolerance in maize. Our results established that ZmNBR1 mediates the increase in autophagosomes and autophagic activity under drought stress. ZmNBR1 also affects the expression of genes related to autophagy under drought stress. Moreover, we determined that BRASSINOSTEROID INSENSITIVE 1A (ZmBRI1a), a brassinosteroid receptor of the BRI1-like family, interacts with ZmNBR1. Phenotype analysis showed that ZmBRI1a negatively regulates drought tolerance in maize, and genetic analysis indicated that ZmNBR1 acts upstream of ZmBRI1a in regulating drought tolerance. Furthermore, ZmNBR1 facilitates the autophagic degradation of ZmBRI1a under drought stress. Taken together, our results reveal that ZmNBR1 regulates the expression of autophagy-related genes, thereby increasing autophagic activity and promoting the autophagic degradation of ZmBRI1a under drought stress, thus enhancing drought tolerance in maize. These findings provide new insights into the autophagy degradation of brassinosteroid signaling components by the autophagy receptor NBR1 under drought stress.