Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target.

Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, the development of more efficacious strategies and the exploration of potential targets for patients with metastatic breast cancer are urgently needed. The data of six patients with breast cancer brain metastases (BCBrM) from two centres were collected, and a comprehensive landscape of the entire tumour ecosystem was generated through the utilisation of single-cell RNA sequencing. We utilised the Monocle2 and CellChat algorithms to investigate the interrelationships among each subcluster. In addition, multiple signatures were collected to evaluate key components of the subclusters through multi-omics methodologies. Finally, we elucidated common expression programs of malignant cells, and experiments were conducted in vitro and in vivo to determine the functions of interleukin enhancer-binding factor 2 (ILF2), which is a key gene in the metastasis module, in BCBrM progression. We found that subclusters in each major cell type exhibited diverse characteristics. Besides, our study indicated that ILF2 was specifically associated with BCBrM, and experimental validations further demonstrated that ILF2 deficiency hindered BCBrM progression. Our study offers novel perspectives on the heterogeneity of BCBrM and suggests that ILF2 could serve as a promising biomarker or therapeutic target for BCBrM.

Methylated ctDNA predicts early recurrence risk in patients undergoing resection of initially unresectable colorectal cancer liver metastases.

Background: Patients with initially unresectable colorectal cancer liver metastases (IU-CRLM) might benefit from using an effective systemic treatment followed by resection of liver metastases but the curative success rate is quite low. Indeed, nearly one-third of patients exhibit early recurrence within the first 6 months after surgery, and these individuals often have poor overall survival. Objectives: This study aims to clarify the application value of serial circulating tumor DNA (ctDNA) analysis in predicting the clinical outcome of IU-CRLM patients following liver metastasectomy. Design: A retrospective study was conducted on a cohort of patients with IU-CRLM between February 2018 and April 2021. Methods: Plasma samples at different time points during CRLM treatment [baseline (BL), preoperation (PRE), postoperation (POST), end-of-treatment (EOT), and progressive disease (PD)] were retrospectively collected from patients with initially unresectable CRLM enrolled at the Sun Yat-sen University Cancer Center. Dynamic changes of SEPTIN 9 (SEPT9) and Neuropeptide Y (NPY) methylated circulating tumor DNA (MetctDNA) levels in serial plasma samples were detected using droplet-digital PCR (ddPCR). Results: SEPT9 and NPY genes were hypermethylated in colon cancer cell lines and tissues while no difference was observed between primary and metastatic tumors. Patients with MetctDNA positive at POST or EOT had significantly lower recurrence-free survival (RFS) compared to patients with MetctDNA negative at these time points [POST: Hazard ratio (HR) 9.44, 95% confidence interval (CI) 5.15-17.30, p < 0.001; EOT: HR 11.48, 95% CI 3.27-40.31, p < 0.001]. Multivariate analysis demonstrated that POST (OR 33.96, 95% CI 4.03-286.10, p = 0.001) and EOT (OR 18.36, 95% CI 1.14-295.71, p = 0.04) MetctDNA was an independent risk factor for early recurrence. Time-dependent receiver operating characteristic curve (T-ROC) analysis revealed that area under the curve (AUC) value was greatest at the relapse time point of 6 months post-intervention, with POST-AUC and EOT-AUC values of 0.74 (95% CI 0.66-0.81) and 0.73 (95% CI 0.53-0.94), respectively. Serial MetctDNA analysis showed that RFS was significantly lower in patients with no MetctDNA clearance compared with those with MetctDNA clearance (HR 26.05, 95% CI 4.92-137.81, p < 0.001). Conclusion: Our study confirmed that serial ctDNA analysis of NPY and SEPT9 gene methylation could effectively predict early recurrence in IU-CRLM patients, especially at POST and EOT.

Covalent-organic framework nanobionics for robust cytoprotection.

We present a novel study introducing a durable and robust covalent-organic framework (COF) nanocoating, developed in situ on living cells. This COF nanocoating demonstrates remarkable resistance against a diverse range of lethal stressors, including high temperature, extreme pH, ultraviolet radiation, toxic metal ions, organic pollutants, and strong oxidative stress. Notably, the nanocoating exhibits exceptional cell survival enhancement under high temperature and strongly acidic conditions, an aspect yet unexplored in the case of metal-organic framework nanocoatings and other nanomaterials. Moreover, functionalization of the nanocoating with an exogenous enzyme catalase enables yeast fermentation and ethanol production even under strong oxidative stress. Our findings establish the durable and robust COF nanocoating as a reliable platform for safeguarding vulnerable microorganisms to allow their utilisation in a wide range of adverse environments.

Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.

Single-cell histone chaperones patterns guide intercellular communication of tumor microenvironment that contribute to breast cancer metastases.

BACKGROUND: Histone chaperones (HCs) are crucial for governing genome stability and gene expression in multiple cancers. However, the functioning of HCs in the tumor microenvironment (TME) is still not clearly understood. METHODS: Self-tested single-cell RNA-seq data derived from 6 breast cancer (BC) patients with brain and liver metastases were reanalyzed by nonnegative matrix factorization (NMF) algorithm for 36 HCs. TME subclusters were observed with BC and immunotherapy public cohorts to assess their prognosis and immune response. The biological effect of HSPA8, one of the HCs, was verified by transwell assay and wound-healing assays. RESULTS: Cells including fibroblasts, macrophages, B cells, and T cells, were classified into various subclusters based on marker genes. Additionally, it showed that HCs might be strongly associated with biological and clinical features of BC metastases, along with the pseudotime trajectory of each TME cell type. Besides, the results of bulk-seq analysis revealed that TME cell subclusters mediated by HCs distinguished significant prognostic value for BC patients and were relevant to patients' immunotherapy responses, especially for B cells and macrophages. In particular, CellChat analysis exhibited that HCs-related TME cell subclusters revealed extensive and diverse interactions with malignant cells. Finally, transwell and wound-healing assays exhibited that HSPA8 deficiency inhibited BC cell migration and invasion. CONCLUSIONS: Collectively, our study first dissected HCs-guided intercellular communication of TME that contribute to BC metastases.

Circular RNA: A promising new star of vaccine.

Circular RNAs (circRNAs) are a class of single-stranded RNAs with covalently closed structures. Owing to their not having 3' or 5' ends, circRNAs are highly durable and insusceptible to exonuclease-mediated degradation. Moreover, some circRNAs with certain structures are translatable, making them novel vaccines. Vaccines are efficient tools for immunotherapy, such as for the prevention of infectious diseases and cancer treatment. The immune system is activated during immunotherapy to fight against abnormal allies or invaders. CircRNA vaccines represent a potential new avenue in the vaccine era. Recently, several circRNA vaccines have been synthesized and tested in vitro and in vivo. Our review briefly introduces the current understanding of the biology and function of translatable circRNAs, molecular biology, synthetic methods, delivery of circRNA, and current circRNA vaccines. We also discussed the challenges and future directions in the field by summarizing the developments in circRNA vaccines in the past few years.

Deep learning-derived spatial organization features on histology images predicts prognosis in colorectal liver metastasis patients after hepatectomy.

Histopathological images of colorectal liver metastases (CRLM) contain rich morphometric information that may predict patients' outcomes. However, to our knowledge, no study has reported any practical deep learning framework based on the histology images of CRLM, and their direct association with prognosis remains largely unknown. In this study, we developed a deep learning-based framework for fully automated tissue classification and quantification of clinically relevant spatial organization features (SOFs) in H&E-stained images of CRLM. The SOFs based risk-scoring system demonstrated a strong and robust prognostic value that is independent of the current clinical risk score (CRS) system in independent clinical cohorts. Our framework enables fully automated tissue classification of H&E images of CRLM, which could significantly reduce assessment subjectivity and the workload of pathologists. The risk-scoring system provides a time- and cost-efficient tool to assist clinical decision-making for patients with CRLM, which could potentially be implemented in clinical practice.

Nanobiohybrids: Synthesis strategies and environmental applications from micropollutants sensing and removal to global warming mitigation.

Micropollutants contamination and global warming are critical environmental issues that require urgent attention due to natural and anthropogenic activities posing serious threats to human health and ecosystems. However, traditional technologies, such as adsorption, precipitation, biodegradation, and membrane separation, are facing challenges of low utilization efficiency of oxidants, poor selectivity, and complex in-situ monitoring operations. To address these technical bottlenecks, nanobiohybrids, synthesized by interfacing the nanomaterials and biosystems, have recently emerged as eco-friendly technologies. In this review, we summarize the synthesis approaches of nanobiohybrids and their utilization as emerging environmental technologies for addressing environmental problems. Studies demonstrate that enzymes, cells, and living plants can be integrated with a wide range of nanomaterials including reticular frameworks, semiconductor nanoparticles and single-walled carbon nanotubes. Moreover, nanobiohybrids demonstrate excellent performance for micropollutant removal, carbon dioxide conversion, and sensing of toxic metal ions and organic micropollutants. Therefore, nanobiohybrids are expected to be environmental friendly, efficient, and cost-effective techniques for addressing environmental micropollutants issues and mitigating global warming, benefiting both humans and ecosystems alike.

Strategies for managing group caregiving following hip-fracture surgery among family members: A grounded theory study.

BACKGROUND: Family members in many countries often share caregiving responsibilities for an older relative recovering from an injury. However, few studies have examined strategies employed when multiple family members provide care for an older relative recovering from hip-fracture surgery. OBJECTIVE: This study aimed to understand family group caregiving strategies when two or more family members provide caregiving for an older relative recovering from hip-fracture surgery. METHODS: This study used a grounded theory design. Semistructured interviews were conducted over 1 year with 13 Taiwanese family caregivers from five families. Caregivers shared caregiving responsibilities for an older relative (62-92 years of age) recovering from hip-fracture surgery. Transcribed interviews were analysed using open, axial and selective coding. RESULTS: The core category describing caregiving among family members was 'Preventive Group Management: strategies for family group caregiving'. Three strategies were employed: explicit division of labour (two stem/patriarchal families and one older two-generation/democratic family); disconnected caregiving (one nuclear/noncommunicative family) and patriarchal caregiving (one extended/traditional Chinese family). Strategies reflected family type, structure, cultural values, communication patterns and available outside support. Components of family group caregiving involved family type's division of labour, approaches to caregiving and implementation challenges and allowed family caregivers to maximise safety and stability and prevent harmful events during their relative's recovery from surgery. CONCLUSIONS: There was no one-size-fits-all approach for the strategies of family group caregiving. Components of Preventive Group Management varied with family type, cultural values, communication patterns and available outside support. Healthcare professionals should be sensitive to the dynamics of family caregivers. IMPLICATIONS FOR PRACTICE: Enhance group management for family caregivers by developing interventions to optimize collaboration, thereby better addressing the needs of older adults recovering from hip fracture surgery.

Formation Mechanisms of Nitro Products from Transformation of Aliphatic Amines by UV/Chlorine Treatment.

Formation of nitrogenous disinfection byproducts from aliphatic amines is a widespread concern owing to the serious health risks associated with them. However, the mechanisms of transforming aliphatic amines and forming nitro products in the UV/chlorine process have rarely been discussed, which are investigated in this work. Initially, secondary amines (R1R2NH) are transformed into secondary organic chloramines (R1R2NCl) via chlorination. Subsequently, radicals, such as HO• and Cl•, are found to contribute predominantly to such transformations. The rate constants at which HO•, Cl•, and Cl2•- react with R1R2NCl are (2.4-5.1) × 109, (1.5-3.8) × 109, and (1.2-6.1) × 107 M-1 s-1, respectively. Consequently, R1R2NCl are transformed into primary amines (R1NH2/R2NH2) and chlorinated primary amines (R1NHCl/R2NHCl and R1NCl2/R2NCl2) by excess chlorine. Furthermore, primarily driven by UV photolysis, chlorinated primary amines can be transformed into nitroalkanes with conversion rates of ∼10%. Dissolved oxygen and free chlorine play crucial roles in forming nitroalkanes, and post-chlorination can further form chloronitroalkanes, such as trichloronitromethane (TCNM). Radicals are involved in forming TCNM in the UV/chlorine process. This study provides new insights into the mechanisms of transforming aliphatic amines and forming nitro products using the UV/chlorine process.

Insight into Bioactivity of In-situ Trapped Enzyme-Covalent-Organic Frameworks.

Selecting a suitable support material for enzyme immobilization with excellent biocatalytic activity and stability is a critical aspect in the development of functional biosystems. The highly stable and metal-free properties of covalent-organic frameworks (COFs) make them ideal supports for enzyme immobilization. Herein, we constructed three kinds of COFs via a biofriendly and one-pot synthetic strategy at room temperature in aqueous solution. Among the three developed COFs (COF-LZU1, RT-COF-1 and ACOF-1), the horseradish peroxidase (HRP)-incorporated COF-LZU1 is found to retain the highest activity. Structural analysis reveals that a weakest interaction between the hydrated enzyme and COF-LZU1, an easiest accessibility by the COF-LZU1 to the substrate, as well as an optimal conformation of enzyme together promote the bioactivity of HRP-COF-LZU1. Furthermore, the COF-LZU1 is revealed to be a versatile nanoplatform for encapsulating multiple enzymes. The COF-LZU1 also offers superior protection for the immobilized enzymes under harsh conditions and during recycling. The comprehensive understanding of interfacial interactions of COF host and enzyme guest, the substrate diffusion, as well as the enzyme conformation alteration within COF matrices represents an opportunity to design the ideal biocatalysts and opens a broad range of applications of these nanosystems.

Dissecting the role of cancer-associated fibroblast-derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single-cell transcriptomic study.

INTRODUCTION: Cancer-associated fibroblasts (CAFs) are correlated with the immunotherapy response. However, the culprits that link CAFs to immunotherapy resistance are still rarely investigated in real-world studies. OBJECTIVES: This study aims to systematically assess the landscape of fibroblasts in cancer patients by combining single-cell and bulk profiling data from pan-cancer cohorts. We further sought to decipher the expression, survival predictive value and association with immunotherapy response of biglycan (BGN), a proteoglycan in the extracellular matrix, in multiple cohorts. METHODS: Pan-cancer tumor bulks and 27 single-cell RNA sequencing cohorts were enrolled to investigate the correlations and crosstalk between CAFs and tumor or immune cells. Specific secreting factors of CAFs were then identified by expression profiling at tissue microdissection, isolated primary fibroblasts and single-cell level. The role of BGN was further dissected in additional three bulk and five single-cell profiling datasets from immunotherapy cohorts and validated in real-world patients who have received PD-1 blockade using immunohistochemistry and immunofluorescence. RESULTS: CAFs were closely correlated with immune components. Frequent crosstalk between CAFs and other cells was revealed by the CellChat analysis. Single-cell regulatory network inference and clustering identified common and distinct regulators for CAFs across cancers. The BGN was determined to be a specific secreting factor of CAFs. The BGN served as an unfavourable indicator for overall survival and immunotherapy response. In the real-world immunotherapy cohort, patients with high BGN levels presented a higher proportion of poor response compared with those with low BGN (46.7% vs. 11.8%) and a lower level of infiltrating CD8+ T cells was also observed. CONCLUSIONS: We highlighted the importance of CAFs in the tumor microenvironment and revealed that the BGN, which is mainly derived from CAFs, may be applicable in clinical practice and serve as a therapeutic target in immunotherapy resistance.

Site-Specific Antibody Assembly on Nanoparticles via a Versatile Coating Method for Improved Cell Targeting.

Antibody-nanoparticle conjugates are promising candidates for precision medicine. However, developing a controllable method for conjugating antibodies to nanoparticles without compromising the antibody activity represents a critical challenge. Here, a facile and generalizable film-coating method is presented using zeolitic imidazole framework-8 (ZIF-8) to immobilize antibodies on various nanoparticles in a favorable orientation for enhanced cell targeting. Different model and therapeutic antibodies (e.g., Herceptin) are assembled on nanoparticles via a biomineralized film-coating method and exhibited high antibody loading and targeting efficiencies. Importantly, the antibodies selectively bind to ZIF-8 via their Fc regions, which favorably exposes the functional Fab regions to the biological target, thus improving the cell targeting ability of antibody-coated nanoparticles. In combination, molecular dynamics simulations and experimental studies on antibody immobilization, orientation efficiency, and biofunctionality collectively demonstrate that this versatile site-specific antibody conjugation method provides effective control over antibody orientation and leads to improved cell targeting for a variety of nanoparticles.

Locking the Ultrasound-Induced Active Conformation of Metalloenzymes in Metal-Organic Frameworks.

Enhancing the enzymatic activity inside metal-organic frameworks (MOFs) is a critical challenge in chemical technology and bio-technology, which, if addressed, will broaden their scope in energy, food, environmental, and pharmaceutical industries. Here, we report a simple yet versatile and effective strategy to optimize biocatalytic activity by using MOFs to rapidly "lock" the ultrasound (US)-activated but more fragile conformation of metalloenzymes. The results demonstrate that up to 5.3-fold and 9.3-fold biocatalytic activity enhancement of the free and MOF-immobilized enzymes could be achieved compared to those without US pretreatment, respectively. Using horseradish peroxidase as a model, molecular dynamics simulation demonstrates that the improved activity of the enzyme is driven by an opened gate conformation of the heme active site, which allows more efficient substrate binding to the enzyme. The intact heme active site is confirmed by solid-state UV-vis and electron paramagnetic resonance, while the US-induced enzyme conformation change is confirmed by circular dichroism spectroscopy and Fourier-transform infrared spectroscopy. In addition, the improved activity of the biocomposites does not compromise their stability upon heating or exposure to organic solvent and a digestion cocktail. This rapid locking and immobilization strategy of the US-induced active enzyme conformation in MOFs gives rise to new possibilities for the exploitation of highly efficient biocatalysts for diverse applications.

Regulating the Coordination Environment of Mesopore-Confined Single Atoms from Metalloprotein-MOFs for Highly Efficient Biocatalysis.

Single-atom catalysts (SACs) exhibit unparalleled atomic utilization and catalytic efficiency, yet it is challenging to modulate SACs with highly dispersed single-atoms, mesopores, and well-regulated coordination environment simultaneously and ultimately maximize their catalytic efficiency. Here, a generalized strategy to construct highly active ferric-centered SACs (Fe-SACs) is developed successfully via a biomineralization strategy that enables the homogeneous encapsulation of metalloproteins within metal-organic frameworks (MOFs) followed by pyrolysis. The results demonstrate that the constructed metalloprotein-MOF-templated Fe-SACs achieve up to 23-fold and 47-fold higher activity compared to those using metal ions as the single-atom source and those with large mesopores induced by Zn evaporation, respectively, as well as up to a 25-fold and 1900-fold higher catalytic efficiency compared to natural enzymes and natural-enzyme-immobilized MOFs. Furthermore, this strategy can be generalized to a variety of metal-containing metalloproteins and enzymes. The enhanced catalytic activity of Fe-SACs benefits from the highly dispersed atoms, mesopores, as well as the regulated coordination environment of single-atom active sites induced by metalloproteins. Furthermore, the developed Fe-SACs act as an excellent and effective therapeutic platform for suppressing tumor cell growth. This work advances the development of highly efficient SACs using metalloproteins-MOFs as a template with diverse biotechnological applications.

Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer.

Cancer-associated fibroblasts (CAFs) are essential for tumor microenvironment remodeling and correlate with tumor progression. However, interactions between CAFs and tumor cells and immune cells in triple-negative breast cancer (TNBC) are still poorly explored. Here, we investigate the role of CAFs in TNBC and potential novel mediators of their functions. The clustering of classic markers was applied to estimate the relative abundance of CAFs in TNBC cohorts. Primary fibroblasts were isolated from normal and tumor samples. The RNA and culture medium of fibroblasts were subjected to RNA sequencing and mass spectrometry to explore the upregulated signatures in CAFs. Microdissection and single-cell RNA sequencing datasets were used to examine the expression profiles. CAFs were associated with hallmark signalings and immune components in TNBC. Clustering based on CAF markers in the literature revealed different CAF infiltration groups in TNBC: low, medium and high. Most of the cancer hallmark signaling pathways were enriched in the high CAF infiltration group. Furthermore, RNA sequencing and mass spectrometry identified biglycan (BGN), a soluble secreted protein, as upregulated in CAFs compared to normal cancer-adjacent fibroblasts (NAFs). The expression of biglycan was negatively correlated with CD8 + T cells. Biglycan indicated poor prognostic outcomes and might be correlated with the immunosuppressive tumor microenvironment (TME). In conclusion, CAFs play an essential role in tumor progression and the TME. We identified an extracellular protein, biglycan, as a prognostic marker and potential therapeutic target in TNBC.

Circulating PD-L1 is associated with T cell infiltration and predicts prognosis in patients with CRLM following hepatic resection.

BACKGROUND: Exosomal PD-L1 (exoPD-L1) could induce immunosuppression functionally, thus impairing patients' survival in melanoma, NSCLC, and gastric cancer. However, no evidence demonstrates the feasibility of circulating exoPD-L1 and soluble PD-L1 (sPD-L1) as biomarkers for prognosis and early recurrence in colorectal liver metastasis (CRLM) patients following hepatectomy or their association with T cell infiltration at liver metastases. METHODS: In cohort 1, exoPD-L1 and sPD-L1 were preoperatively tested using ELISA. CD3, CD8, granzyme B (GB) and PD1 expressed at liver metastases were evaluated using immunohistochemistry. In cohort 2, exoPD-L1 and sPD-L1 were detected at baseline, before hepatectomy, after hepatectomy, and after disease progression. RESULTS: In cohort 1, higher preoperative exoPD-L1 or sPD-L1 significantly impaired RFS (exoPD-L1, P = 0.0043; sPD-L1, P = 0.0041) and OS (exoPD-L1, P = 0.0034; sPD-L1, P = 0.0061). Furthermore, preoperative exoPD-L1 was negatively correlated with CD3 + T-lymphocytes infiltrated at tumor center (CT), and GB and PD1 were expressed at tumor invasive margin (IM). Preoperative sPD-L1 was negatively correlated with CD3 + and CD8 + T-lymphocytes' infiltration at IM and CT, GB and PD1 expression at IM. In cohort 2, exoPD-L1 and sPD-L1 levels decreased following hepatectomy but increased when tumor progressed. Moreover, higher postoperative exoPD-L1 and sPD-L1 or a small reduction in exoPD-L1 and sPD-L1 levels after hepatectomy suggested higher early recurrence rate. CONCLUSIONS: Both preoperative exoPD-L1 and sPD-L1 had promising prognostic values and were associated with T cell infiltration at liver metastases in CRLM patients following hepatectomy. Dynamically tracking exoPD-L1 and sPD-L1 levels could monitor disease status and detect early recurrence.

De Novo Engineering of Metal-Organic Framework-Printed In Vitro Diagnostic Devices for Specific Capture and Release of Tumor Cells.

Herein, a paper-based in vitro diagnostic device (IVD) is developed via inkjet printing of de novo engineered, boronic acid-rich metal-organic frameworks (BMOFs). The newly developed BMOFs simultaneously possess crystalline and amorphous structure, mesopore size, large surface area, and retain a high level of boronic acid integration. After printing the BMOFs on the filter paper, the BMOF-printed paper IVD shows a rapid response time (40 min) towards cancer cell capture and its maximum cell capture capacity reaches approximately (4.5 ±1.1) ×104 cells cm-2 . Furthermore, the BMOF-printed IVD shows nine times higher capture ability of cancer cells than non-cancerous cells, suggesting its excellent selectivity. Importantly, the pH-tunable affinity of BMOF to glucose enables its dual-responsive behavior without affecting cell viability. In addition, a desired cell pattern could be achieved by directly drawing BMOFs onto a silicon substrate, highlighting its capacity as a miniaturized device for tumor cell capture and analysis. This simple and label-free nanoplatform enables new opportunities for designing MOF-based smart devices for diverse biomedical applications such as a cost-effective IVD technologies for cancer diagnosis, genotyping, and prognosis.

A Prehepatectomy Circulating Exosomal microRNA Signature Predicts the Prognosis and Adjuvant Chemotherapeutic Benefits in Colorectal Liver Metastasis.

BACKGROUND: The clinical risk score (CRS) for prediction and treatment decision in colorectal liver metastasis (CRLM) is important, but imprecise. Exosomal miRNAs play critical roles in CRLM-related biological behavior. However, an exosomal miRNA score system for predicting posthepatectomy survival and the adjuvant chemotherapy benefit of CRLM remains elusive. METHODS: miRNA sequencing was used to identify differentially expressed miRNAs, and the LASSO model was used to select miRNAs to construct the intent model. The predictive performance of the model was evaluated by the area under the ROC curve (AUC) in the training, internal validation, and external validation cohorts. RESULTS: Sixteen differentially expressed exosomal miRNAs were identified, and four miRNAs were selected for model construction. Our model performed well in predicting prognosis with five-year AUCs of 0.70 (95% CI: 0.59-0.81), 0.70 (0.61-0.81), and 0.72 (057-0.86) in the training, internal, and external validation cohorts, respectively. miRNA classifier high-risk patients had better survival benefit from adjuvant chemotherapy regardless of CRS. All four miRNAs target signaling molecules play crucial roles in colorectal cancer metastasis, vesicle-related processing, and T cell activation. It also negatively correlated with the liver metastasis Immunoscore. CONCLUSION: We developed a circulating exosomal miRNA signature that can predict the prognosis and guide adjuvant chemotherapy decisions after hepatectomy in CRLM.

Superstructured mesocrystals through multiple inherent molecular interactions for highly reversible sodium ion batteries.

Soft structures in nature, such as supercoiled DNA and proteins, can organize into complex hierarchical architectures through multiple noncovalent molecular interactions. Identifying new classes of natural building blocks capable of facilitating long-range hierarchical structuring has remained an elusive goal. We report the bottom-up synthesis of a hierarchical metal-phenolic mesocrystal where self-assembly proceeds on different length scales in a spatiotemporally controlled manner. Phenolic-based coordination complexes organize into supramolecular threads that assemble into tertiary nanoscale filaments, lastly packing into quaternary mesocrystals. The hierarchically ordered structures are preserved after thermal conversion into a metal-carbon hybrid framework and can impart outstanding performance to sodium ion batteries, which affords a capability of 72.5 milliampere hours per gram at an ultrahigh rate of 200 amperes per gram and a 90% capacity retention over 15,000 cycles at a current density of 5.0 amperes per gram. This hierarchical structuring of natural polyphenols is expected to find widespread applications.