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.

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.

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.

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.

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.

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.

Metal-Organic Frameworks as a Versatile Materials Platform for Unlocking New Potentials in Biocatalysis.

Biocatalysts immobilization with nanomaterials has promoted the development of biocatalysis significantly and made it an indispensable part of catalysis industries nowadays. Metal-organic frameworks (MOFs), constructed from organic linkers and metal ions or clusters, have raised significant interests for biocatalysts immobilization in recent years. The diversity of building units, molecular-scale tunability, and modular synthetic routes of MOFs greatly expand its ability as the host to integrate with biocatalysts. In this review, the general synthetic strategies of MOFs with biocatalysts are first summarized. Then, the recent progress of MOFs as a versatile host for a series of biocatalysts, including natural enzymes, nanozymes, and organism-based biocatalysts, followed by the introduction of MOFs themselves as biocatalysts, is discussed. Furthermore, the stimuli-responsive properties of MOFs themselves or the additional functionalization of protein, polymer, and peptide within/on MOF that enable the biocatalysts with the controllable and tunable behavior are also summarized, which could unlock new potentials in biocatalysis. Finally, a perspective of the upcoming challenges, potential impacts, and future directions of biocatalytic MOFs is provided.

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.

Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study.

Background Gemcitabine plus cisplatin is regarded as the standard first-line therapy for patients with advanced biliary tract cancer (BTC); however, no standard chemotherapy has yet been recommended after treatment failure. Modified FOLFIRINOX (mFOLFIRINOX) appears to be a better-tolerated regimen, which leads to improved survival in metastatic pancreatic cancer that has histological and molecular similarities with BTC. We assessed the efficacy and safety of mFOLFIRINOX as salvage therapy in advanced BTC patients who were refractory to previous chemotherapy. Methods A total of 15 consecutive patients with documented unresectable locally advanced or metastatic BCT who received the mFOLFIRINOX regimen were included in the study. Patients were intravenously administrated with oxaliplatin (65 mg/m2), leucovorin (400 mg/m2), irinotecan (150 mg/m2), and continuous infusion of fluorouracil (2400 mg/m2) over 46 h. The objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were recorded. Results At least three cycles of mFOLFIRINOX regimen were delivered to 15 patients with a median number of 6.0 cycles (IQR 5.5-11.0). The median duration of treatment was 3.8 months (IQR 2.9-8.5). Four patients (26.7%) achieved an ORR, and 12 patients (80.0%) had a DCR. The median PFS and OS were 6.7 months (95%CI 2.3-11.1) and 13.2 months (95%CI 7.3-19.1), respectively. Five patients (33.3%) had treatment-related grade 3/4 AEs. The most common grade 3/4 AE was neutropenia (n = 3, 20.0%), while there was no occurrence of febrile neutropenia. Conclusion Treatment with mFOLFIRINOX has promising efficacy and favorable tolerance as salvage therapy in patients with refractory advanced BCT.

Hierarchically Porous Biocatalytic MOF Microreactor as a Versatile Platform towards Enhanced Multienzyme and Cofactor-Dependent Biocatalysis.

Metal-organic frameworks (MOFs) have recently emerged as excellent hosting matrices for enzyme immobilization, offering superior physical and chemical protection for biocatalytic reactions. However, for multienzyme and cofactor-dependent biocatalysis, the subtle orchestration of enzymes and cofactors is largely disrupted upon immobilizing in the rigid crystalline MOF network, which leads to a much reduced biocatalytic efficiency. Herein, we constructed hierarchically porous MOFs by controlled structural etching to enhance multienzyme and cofactor-dependent enzyme biocatalysis. The expanded size of the pores can provide sufficient space for accommodated enzymes to reorientate and spread within MOFs in their lower surface energy state as well as to decrease the inherent barriers to accelerate the diffusion rate of reactants and intermediates. Moreover, the developed hierarchically porous MOFs demonstrated outstanding tolerance to inhospitable surroundings and recyclability.

Development and validation of a stromal immune phenotype classifier for predicting immune activity and prognosis in triple-negative breast cancer.

Our study aims to construct a prognosis-related immune phenotype classifier for predicting clinical prognosis and immune activity in triple-negative breast cancer (TNBC). A total of 237 patients with TNBC from Sun Yat-sen University Cancer Center (SYSUCC) and 533 patients with TNBC from public datasets were included in our study. A stromal immune quantified index was generated with a LASSO Cox regression model based on five prognosis-related immune cells evaluated by CIBERSORT or IHC and was used to determine immune phenotypes. Immune features were evaluated in the samples before chemotherapy. A total of 119 patients in the SYSUCC training cohort were classified into immune Phenotypes A and B according to the density of stromal CD4+ T cells, γδ T cells, monocytes, M1 macrophages and M2 macrophages. Phenotype A predicted better survival than Phenotype B, and the classification was further validated in the testing cohort of 118 patients and the validation cohort of 533 patients. In the combined cohort, significant differences were found in Phenotype A compared to Phenotype B for the 5-year overall survival (83.5% vs 65.8%, respectively, P < .01) and the 5-year disease-free survival (87.3% vs 76.0%, respectively, P < .01). In Phenotype A, immune-related pathways were significantly enriched, and a higher level of immune checkpoint molecules, including PD-L1, PD-1 and CTLA-4, could be observed. The immune phenotype classification was an independent prognostic indicator for TNBC and might serve as a potential predictor for immune activity within the tumor microenvironment.

Histopathological growth patterns correlate with the immunoscore in colorectal cancer liver metastasis patients after hepatectomy.

Various scoring systems have been proposed to predict the postoperative prognosis of colorectal liver metastasis (CRLM), including the clinical risk score (CRS), the immunoscore and so on. Recently, histopathological growth patterns (HGPs) have been recognized. However, the correlation between HGPs and the immunoscore, and their prognostic values in patients with CRLM after liver resection remain undetermined. In this study, HGPs were retrospectively evaluated in H&E-stained slides from 166 CRLM patients. The immunoscore was calculated according to the densities of immunostained CD3 + and CD8 + cells. A risk score combining HGPs, the immunoscore and the CRS was defined and divided patients into the low-, medium- and high-risk group. Our results showed that the densities of CD3 + and CD8 + cells were higher in the desmoplastic HGP (dHGP) group than in the non-dHGP group, and the proportion of high immunoscores was also higher in the dHGP group (51.9% vs. 33.0%, respectively, P = 0.020). Patients with the dHGP had significantly longer relapse-free survival (RFS) and overall survival (OS) than those with the non-HGP. The low-risk group showed significantly higher 2-year RFS and 5-year OS rates than the other two groups (RFS: 76.2%, 43.7% and 33.1%, respectively; P < 0.001; OS: 89.7%, 54.4% and 33.3%, respectively; P < 0.001). In conclusion, the dHGP correlates with relatively high immunoscores, predicting a favorable prognosis independent of the immunoscore and CRS. A novel risk score combining HGPs, the immunoscore and the CRS may be used for the stratification of CRLM patients' survival.

Multi-enzyme Cascade Reactions in Metal-organic Frameworks.

Multi-enzyme cascade reactions are indispensable in biotechnology and many industrial (bio)chemical processes. However, most natural enzymes have poor stability and reusability, and tend to inactivate in toxic media or high temperature, which significantly limit their broader applications. Metal-organic frameworks (MOFs) are promising candidates for enzymes immobilization to produce nanocomposite structures that not only could shield the enzymes from harsh environments, but also facilitate selective diffusion of substrates and intermediates to the reactive site via their tailorable and ordered pore network. Multi-enzyme cascade reactions in MOFs have recently attracted considerable attention. This Personal Account discusses the different strategies for multi-enzyme-MOF interfaces and their cutting-edge applications from biosensing and catalytic nanomedicine to artificial/hybrid cells. At last, we provide a critical evaluation and future prospects to outline future research directions.

Metal-Organic Framework-Plant Nanobiohybrids as Living Sensors for On-Site Environmental Pollutant Detection.

Photoluminescent metal-organic frameworks (MOFs) were grown in a living plant (Syngonium podophyllum) via immersing their roots in an aqueous solution of disodium terephthalate and terbium chloride hexahydrate sequentially for 12 h without affecting their viability. Then, app-assisted living MOF-plant nanobiohybrids were used for the detection of various toxic metal ions and organic pollutants. Their performance and sensing mechanism were also evaluated. The results demonstrated that the living plants served as self-powered preconcentrators via their passive fluid transport systems and accumulated the pollutants around the embedded MOFs, resulting in relative changes in fluorescence intensity. Therefore, the living MOF-plant nanobiohybrids initiate superior selectivity and sensitivity (0.05-0.5 µM) in water for Ag+, Cd2+, and aniline with a "turn-up" fluorescence response and for Fe3+ and Cu2+ with "turn-down" fluorescence response in the linear range of 0.05-10 µM with excellent precision and accuracy of 5 and 10%, respectively. With the easy-to-read visual signals under ultraviolet light, the app translates plant luminescent signals into digital information on a smartphone for on-site monitoring of environmental pollutants with high sensitivity and specificity. These results suggest that interfacing synthetic and living materials may contribute to the development of smart sensors for on-site environmental pollutant sensing with high accuracy.

Algal toxicity induced by effluents from textile-dyeing wastewater treatment plants.

This research aimed to evaluate the alga Scenedesmus obliquus toxicity induced by textile-dyeing effluents (TDE). The toxicity indicator of TDE in alga at the physiological (algal growth), biochemical (chlorophyll-a (Chl-a) synthesis and superoxide dismutase (SOD) activity) and structural (cell membrane integrity) level were investigated. Then we further study the relationship among toxicity indicators at physiological and biochemical level, and supplemented by research on algal biomacromolecules. According to the analysis of various endpoints of the alga, the general sensitivity sequence of toxicity endpoints of Scenedesmus obliquus was: SOD activity > Chl-a synthesis > algal growth. The stimulation rate of SOD activity increased from day 3 (57.25%~83.02%) to day 6 (57.25%~103.81%), and then decreased on day 15 (-4.23%~-32.96%), which indicated that the antioxidant balance system of the algal cells was destroyed. The rate of Chl-a synthesis inhibition increased gradually, reaching 19.70%~79.39% on day 15, while the rate of growth inhibition increased from day 3 (-12.90%~10.16%) to day 15 (-21.27%~72.46%). Moreover, the algal growth inhibition rate was positively correlated with the inhibition rate of SOD activity or Chl-a synthesis, with the correlation coefficients were 0.6713 and 0.5217, respectively. Algal cells would be stimulating to produce excessive reactive oxygen species, which would cause peroxidation in the cells, thereby destroying chloroplasts, inhibiting chlorophyll synthesis and reducing photosynthesis. With increasing exposure time, irreversible damage to algae can lead to death. This study is expected to enhance our understanding of the ecological risks through algal tests caused by TDE.

Treatment of 3,3'-dimethoxybenzidine in sludge by advance oxidation process: Degradation products and toxicity evaluation.

Studies on the oxidation products of organic pollutants and their toxicity in textile dyeing sludge after the sludge was treated by the advance oxidation processes were limited, since textile dyeing sludge was a complicated mixture. For the first time, simulated sludge was used to study the degradation mechanism of 3,3'-dimethoxybenzidine (DMB) during the combined ultrasound-Mn(VII) treatment. The toxicity of DMB and its products was also evaluated. The results indicated that the compositions and microstructures of polyaluminium chloride (PAC)- and polyferric sulphate (PFS)-based simulated sludge were similar to those of real textile dyeing sludge. The optimum conditions of ultrasound-Mn(VII) treatment were: a KMnO4 dosage of 40 µM, an ultrasound power density of 0.36 W cm-3, and a reaction time of 20 min. 98.24% of DMB and 63.04% of total organic carbon (TOC) in the simulated sludge were removed. Six products, that is, 2-nitroanisole, 3-methoxy-4-nitrophenol, vanillylmandelic acid, vanillyl alcohol, m-anisic acid, and benzoic acid, were identified by GC-MS and LC-MS-MS. It was noted that all of these identified products were also detected in the real textile dyeing sludge after the ultrasound-Mn(VII) treatment. All of them were less toxic than DMB. Moreover, 53.30% and 54.80% of toxicity toward the alga Desmodesmus subspicatus and the bacterium Vibrio fischeri were removed in simulated sludge, respectively. Therefore, simulated sludge was helpful for studying a pollutant's degradation mechanism in the complex sludge mixtures. The results would also provide some useful suggestions for the sludge disposal after the sludge was treated by the advance oxidation processes.

Toxicity evaluation of textile dyeing effluent and its possible relationship with chemical oxygen demand.

Textile dyeing wastewater was the focus of much research because of its adverse effect on aquatic biota. In the present research, textile dyeing influent and effluent samples were collected from four textile dyeing wastewater treatment plants (TDPs) in Guangdong province, China, and their conventional indicators and toxicity were examined to reveal relationships. The relationship between toxicity and chemical oxygen demand (COD) was clearly established at individual TDPs. Results indicated the highest removal efficiencies of 94.4%, 90.6%, 91.9%, 94.6%, 92.8% and 97.5% for TOC, mixed-liquor volatile suspended solids (MLVSS), COD, ammonia nitrogen (NH3-N), total phosphorus (TP) and colour, respectively. The primary clarifier used in TDP3 and TDP4 was beneficial for removing macromolecular organic substances, and membrane filtration and sedimentation basin employed at TDP1 and TDP2, respectively, helped to remove toxic substances. Toxicity to V. fischeri or D. subspicatus was found to be related to certain conventional indicators such as TOC, COD, TP, colour, and MLVSS, and was positively correlated with COD in different textile dyeing effluents (R2 > 0.84). It was recommended that the relationship between toxicity and COD in wastewater should be established individually at each plant. Therefore, this study could be useful in providing suggestions for guiding effluent management when no toxicity experiments were conducted.

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.

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.