Bimetallic Manganese Catalysts: A Route to Controlled and Switchable Polymerization of Lactones.

The sustainable solution to the environmental problem of polymeric materials calls for efficient and well-controlled ring-opening polymerization catalytic systems. Inspired by the highly reactive and stereospecific bimetallic catalysts, three kinds of bimetallic Salen-Mn catalysts supported by biaryl linking moieties are synthesized and applied to polymerization catalysis of lactide (LA) and ϵ-caprolactone (ϵ-CL) in this work. The polymerization is initiated in situ by the ring-opening of epoxide compounds, in which the ionic cocatalyst could accelerate the reaction process. The Mn-Mn coordination effect contributes to the higher activity and iso-selectivity towards LA compared to the mononuclear Salen-Mn catalyst. The reactivity and stereoselectivity are determined by the conformation of catalysts, specifically the Mn-Mn separation and dihedral angle. Finally, the CO2 -controlled switchable polymerizations are carried out with LA and ϵ-CL. The reversibility of the on-off switching operation is influenced by the combination between CO2 molecules and active species. The success in binuclear Salen-Mn catalysts not only expands the range of bimetallic catalyst analogues but also claims the promising potential of Mn-based catalysts in practical and theoretical research.

A Multiple Targeting Nanoprobe for Identifying Cancer Metastatic Sites Based on Detection of Various mRNAs in Circulating Tumor Cells.

Identification of cancer metastatic sites is of importance for adjusting therapeutic interventions and treatment choice. However, identifying the location of metastatic lesions with easy accessibility and high safety is challenging. Here we demonstrate that cancer metastatic sites can be accurately detected by a triple targeting nanoprobe. Through coencapsulating molecular beacons probing a cancer biomarker (CXCR4 mRNA), a lung metastatic biomarker (CTSC mRNA), and a bone metastatic biomarker (JAG1 mRNA), the nanoprobe decorated by SYL3C conjugated hyaluronic acid and ICAM-1 specific aptamer conjugated hyaluronic acid can target diverse phenotyped circulating tumor cells (CTCs) during epithelial-mesenchymal and mesenchymal-epithelial transitions in whole blood for sensitive probing. The detection of CTCs from cancer patients shows that the nanoprobe can provide accurate information to distinguish different cancer metastasis statuses including nonmetastasis, lung metastasis, and bone metastasis. This study proposes an efficient screening tool for identifying the location of distant metastatic lesions via facile blood biopsy.

Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.

Copper-Coordinated Covalent Organic Framework Produced a Robust Fenton-Like Effect Inducing Immunogenic Cell Death of Tumors.

Increasing infiltration of CD8+ T cells can enhance the response rate to immune checkpoint blockade (ICB) therapies. In contrast, immunogenic cell death (ICD) induced by intracellular reactive oxygen species (ROS) is an effective strategy to increase CD8+ T cell infiltration. Cuproptosis is newly defined and reported by Tsvetkov et al. A Cu-coordinated covalent organic framework (COF) in which two valence states of copper ions are simultaneously loaded is prepared. On the one hand, Cu2+ undergoes a valence shift generating Cu+ which acts as an effective Fenton-like reagent to catalyze the production of · OH and 1 O2 from cellular overexpressed H2 O2 , causing DNA damage and lipid peroxidation (LPO), which directly produce cytotoxicity. On the other hand, residual Cu2+ can effectively deplete endogenous cellular glutathione (GSH), converting it into glutathione disulfide (GSSG), further increasing intracellular oxidative stress and reducing the scavenging of ROS, thus further enhancing the Fenton-like effect and bringing toxic effects on tumor cells. The synergy of these two functions achieves ICD, helping for transforming "cold tumor" into "hot tumor" and efficient anti-tumor effects eventually. This work provides new insights into coordinated COF and inspire the development of more versatile COF for biomedical applications.

Electrochemically Controlled Switchable Copolymerization of Lactide, Carbon Dioxide, and Epoxides.

Electrochemical redox-control is an emerging strategy for the regulation of polymerization process without the addition of external oxidants and reductants, which enables the control over composition, microstructure and properties of the polymer products. In this paper, based on the chemical selectivity of heterometallic Salen-Co-Mn complexes of different valences, an electrochemically switchable strategy was developed for the copolymerization of lactide (LA), CO2 and epoxides. The switchable redox reactions endowed this system with the capability to easily synthesize a multi-block copolymer of polylactide (PLA) and polycarbonate (PC). Moreover, the multi-block copolymer could be further modified by introducing various monomers with different microstructures and functional groups.

One-Pot Precision Synthesis of AB, ABA and ABC Block Copolymers via Switchable Catalysis.

The switchable catalysis using a commercial salenMn catalyst was firstly developed and applied in the one-pot selective copolymerization from anhydrides, epoxides, CO2 and ϵ-caprolactone (ϵ-CL) mixtures for the precise synthesis of AB, ABA and novel ABC block copolymers. The observed unique double switch process comprising three different polymerization cycles was rationalized by theoretical calculations. Surprisingly, the first block turned out to be an efficient macromolecular initiator for the consecutive introduction of carbonate linkages into copolymers, albeit with dominant cyclization with the catalyst alone. Further, through the selective reaction on different epoxides, the switchable copolymerization of up to five monomers was achieved yielding well-defined multi-block copolymers with structural diversity and functionality.

Monomer Controlled Switchable Copolymerization: A Feasible Route for the Functionalization of Poly(lactide).

Switchable polymerization is an attractive strategy to enable the sequential selectivity of multi-block polyesters. Besides, these well-defined multi-block polyesters could enable further modification for wider applications. Herein, based on the reversible insertion of CO2 by Salen-MnIII , a new monomer controlled self-switchable polymerization route was developed. Chemoselective ring opening copolymerization of O-carboxyanhydrides (OCAs) and lactide (LA) was explored without cocatalyst. The sequential conversion of OCAs and LA into the polymer chain could form multi-block polyesters. Based on this strategy, a series of multi-block polyesters with different pendant groups were synthesized. Furthermore, by modifying the propargyl-containing copolymers with quaternary ammonium groups, we have realized antibacterial functionalization of PLA. These results imply the potential application of this strategy for the fabrication of functional polymers for biomedical applications.

Multi-Functional Organofluoride Catalysts for Polyesters Production and Upcycling Degradation.

The production and degradation of polyesters are two crucial processes in polyester materials' life cycle. In this work, multi-functional organocatalysts based on fluorides for both processes are described. Organofluorides were developed as catalysts for ring-opening polymerization of lactide (lactone). Compared with a series of organohalides, organofluoride performed the best catalytic reactivity because of the hydrogen bond interaction between F- and alcohol initiator. The Mn values of polyester products could be up to 72 kg mol-1 . With organofluoride catalysts, the ring-opening copolymerization between various anhydrides and epoxides could be established. Furthermore, terpolymerization of anhydride, epoxide, and lactide could be constructed by the self-switchable organofluoride catalyst to yield a block polymer with a strictly controlled polymerization sequence. Organofluorides were also efficient catalysts for upcycling polyester plastic wastes via alcoholysis. Mixed polyester materials could also be hierarchically recycled.

The Design of PAN-Based Janus Membrane with Adjustable Asymmetric Wettability in Wastewater Purification.

In this paper, an environmentally friendly polyacrylonitrile-based (PAN-based) composite membrane with a Janus structure for wastewater treatment was successfully fabricated. To achieve the optimum adsorption of PAN-based Janus composite membrane, the asymmetric wettability was regulated through electrospinning, resulting in TiO2 modifying PAN as the hydrophilic substrate layer, and PCL gaining a different thickness as the hydrophobic layer. The prepared Janus composite membrane (PAN/TiO2-PCL20) showed excellent oil/water separation performance for diverse surfactant-stabilized oil-in-water emulsions. For n-hexane-in-water emulsion, the permeate flux and separation efficiency reached 1344 L m-2 h-1 and 99.52%, respectively. Even after 20 cycles of separation, it still had outstanding reusability and the separation efficiency remained above 99.15%. Meanwhile, the PAN/TiO2-PCL20 also exhibited an excellent photocatalytic activity, and the removal rate for RhB reached 93.2%. In addition, the research revealed that PAN/TiO2-PCL20 possessed good mechanical property and unidirectional water transfer capability. All results indicated that PAN/TiO2-PCL20 with photocatalysis and oil/water separation performance could be used for practical complex wastewater purification.

Solvent-Promoted Catalyst-Free Recycling of Waste Polyester and Polycarbonate Materials.

Polymeric materials are indispensable in our daily lives. However, the generation of vast amounts of waste polymers poses significant environmental and ecological challenges. Instead of resorting to landfilling or incineration, strategies for polymer recycling offer a promising approach to mitigate environmental pollution. Pioneering studies have demonstrated the alcoholysis of waste polyesters and polycarbonates; however, these processes typically require the use of catalysts. Moreover, the development of strategies for catalyst removal and recycling is crucial, particularly in some industrial applications. In contrast, we present a catalyst-free method for the alcoholysis of common polyester and polycarbonate materials into small organic molecules. Certain polar organic solvents exhibit remarkable efficiency in polymer degradation under catalyst-free conditions. Employing these polar solvents, both polymer resins and commercially available products could be effectively degraded via alcoholysis. Our design contributes a straightforward route for recycling waste polymeric materials.

A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBCs), known as an immunologically cold tumor, is difficult to completely eliminate with existing monotherapies, let alone metastasis and recurrence. It is urgent to design a rational combination of multiple therapies to programmatically reconstitute tumor microenvironment (TME) and reverse the immune "cold" into "hot" inflammatory tumors to improve the therapeutic effect. Hence, in this work, a multifunctional nanosystem (FeSH NPs) that integrates metal-polyphenol coordination complex as a photothermal agent and polyphenol, salvianolic acid B (SAB) as immunomodulator is designed and fabricated for synergistic photothermal-immunotherapy of TNBCs combined with anti-PD-L1 antibody. Guided by photothermal/photoacoustic dual-mode imaging, photothermal therapy (PTT) caused by FeSH NPs induces immunogenic cell death (ICD) under 808 nm laser irradiation. Subsequently, the loaded SAB is released with the addition of deferoxamine mesylate (DFO) to remodel TME, specifically TGF-ß inhibition and PD-L1 upregulation, and eliminate the primary tumors. The combination of PTT and TME reprogramming by FeSH NPs further synergizes with anti-PD-L1 antibody to eradicate recurrence and inhibit metastasis of TNBCs concurrently. Given the biosafety of FeSH NPs throughout the lifecycle, this work provides a protocol with high clinical translational promise for comprehensive programmed therapeutics of immunologically cold tumors TNBCs.

pH-Triggered charge-reversal polypeptide nanoparticles for cisplatin delivery: preparation and in vitro evaluation.

A series of pH-responsive random copolymer poly(l-glutamic acid-co-l-lysine) [P(Glu-co-Lys)] were synthesized through the ring-opening polymerization (ROP) of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) and 3-benzyloxycarbonyl-l-lysine N-carboxyanhydride (ZLys-NCA) and the subsequent deprotection. The chemical structure of the P(Glu-co-Lys)s was confirmed by NMR. Critical aggregation concentration and transmission electron microscopy measurements indicated that the P(Glu-co-Lys)s could self-assemble into aggregates in phosphate buffer. The surface charge of P(Glu-co-Lys) aggregates was greatly affected by the solution's pH and l-glutamic acid/l-lysine ratio because the carboxyl and amino groups present on the P(Glu-co-Lys) aggregates could be protonated or deprotonated to become charged. The pH value of the solution at which the surface charge of the P(Glu-co-Lys) aggregates reversed could be manipulated by the feed ratio of BLG-NCA and ZLys-NCA. In vitro methyl thiazolyl tetrazolium assays demonstrated that negatively charged P(Glu-co-Lys)s were nontoxic and biocompatible. Positive charged P(Glu-co-Lys)s showed some cytotoxicity to Hela cells. Cisplatin (CDDP) was used as a model anticancer drug to evaluate the charge-reversal drug delivery system. By the manipulation of CDDP loading content, the surface charge of the CDDP/P(Glu-co-Lys) nanoparticles could be reversed to positive from negative at tumor extracellular pH (pHe 6.5-7.2). An enhanced drug uptake and inhibition of cancer cell proliferation were observed for the tumoral pHe triggered charge-reversal CDDP/P(Glu-co-Lys) drug delivery system. These indicated that the CDDP/P(Glu-co-Lys) nanoparticles could be used as intelligent drug delivery systems for cancer therapy.

Linking downstream river water quality to urbanization signatures in subtropical climate.

Urbanization has several hydro-ecological effects on receiving waters. Hence, understanding how urbanization influences river water quality is essential for proper river management. However, an inappropriate approach that correlates urbanization signatures with water quality may result in spurious correlations. This study aimed to investigate the relationship of urbanization signatures with two key pollutants of stream flows: nutrients and pathogens. In contrast to the commonly used approaches that are based on economic or demographic metrics, our approach represents urbanization signatures using related anthropogenic activities and evaluates the effect of such activities on water quality parameters. The approach was also applied to evaluate the impacts of urbanization on nutrient and pathogen trends in the river waters of Hong Kong. The data were collected for the period of 1986-2020 from the Environmental Protection Department and monthly measurements were performed. Total nitrogen (TN), total phosphorus (TP), Escherichia. coli (E. coli), and fecal coliforms (FC) showed consistently decreasing trends. However, the long-term seasonality of nutrients differed from that of pathogens. TP and TN exhibited homogenous seasonality with an approximately sinusoidal relationship from January to December, whereas the seasonality of pathogens was more complex and not dependent on river flow dilution effects. Additionally, urbanization impacts on station nutrients and pathogen characteristics were found to be unevenly distributed; under high water temperatures, nutrient concentrations were found to be decreased because of the rainfall dilution effect on river flows. Both urban point and diffuse sources of pollution significantly contributed to nutrient pollution in rivers. Furthermore, the concentrations of FC were not highly influenced by suspended solids, and dissolved oxygen was negatively correlated with all pathogens. Furthermore, the river flow rate was found to improve the water quality in terms of both nutrients and pathogens; urban point source pollution and river temperature alteration were shown to mainly contribute to seasonal variations in both nutrients and pathogens.

Valence-variable Catalysts for Redox-controlled Switchable Ring-opening Polymerization.

As a representative class of sustainable polymer materials, biodegradable polymers have attracted increasing interest in recent years. Despite significant advance of related polymerization techniques, realizing high sequence-control and easy-handling in ring-opening (co)polymerizations still remains a central challenge. To this end, a promising solution is the development of valence-variable metal-based catalysts for redox-induced switchable polymerization of cyclic esters, cyclic ethers, epoxides, and CO2 . Through a valence-determined electron effect, the switch between different catalytically active states as well as dormant state contributes to convenient formation of polymer products with desired microstructures and various practical performances. This redox-controlled switchable strategy for controlled synthesis of polymers is overviewed in this Review with a focus on potential applications and challenges for further studies.

Aptamer/Peptide-Functionalized Nanoprobe for Detecting Multiple miRNAs in Circulating Malignant Cells to Study Tumor Heterogeneity.

Identification of diverse biomarkers in heterogenic circulating malignant cells (CMCs) such as circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) has crucial significance in tumor diagnosis. However, it remains a substantial challenge to achieve in situ detection of multiple miRNA markers in living cells in blood. Herein, we demonstrate that an aptamer/peptide-functionalized vector can deliver molecular beacons into targeted living CMCs in peripheral blood of patients for in situ detection of multiple cancer biomarkers, including miRNA-21 (miR-21) and miRNA-221 (miR-221). Based on miR-21 and miR-221 levels, heterogenic CMCs are identified for both nondistant metastatic and distant metastatic cancer patients. CMCs from nondistant metastatic and distant metastatic cancer patients exhibit similar miR-21 levels, while the miR-221 level in CMCs of the distant metastatic cancer patient is higher than that of the nondistant metastatic cancer patient. With the capability to realize precise probing of multiple intracellular biomarkers in living CMCs at the single-cell resolution, the nanoprobe can reveal the tumor heterogeneity and provide useful information for diagnosis and prognosis. The nanoprobe we developed would accelerate the progress toward noninvasive precise cancer diagnosis.

Biodegradable covalent organic frameworks achieving tumor micro-environment responsive drug release and antitumor treatment.

The emergence of nanocarriers has greatly improved the therapeutic efficacy of chemotherapeutic drugs. As emerging nanocarriers, covalent organic frameworks (COFs) have been increasingly used in biomedicine in recent years. However, due to their inherent chemical stability, existing COF nanocarriers hardly undergo in vivo degradation, which brings potential safety hazards to further applications. In this work, we introduce the azo bond into COFs. When the nanocarrier enters the cell, ˙OH generated by the coordinated Fe response to the H2O2 in the cell will break the azo bond and cause the degradation of the framework structure, accelerating the release of internally loaded DOX to effectively realize tumor treatment. We verified the degradation ability of the materials by constructing model compounds, in vitro drug release, MTT assay and antitumor experiments. Compared with the control groups, the degradable COF accelerates the release of DOX and shows a stronger killing effect on 4T1 cells. Serum biochemical analysis and H&E sections of organs show good biocompatibility for both COFs and degradation products. This work provides a new idea for the design of biodegradable COFs in vivo, and greatly explores the potential application of COF materials in the biomedical field.

Multi-Targeting Nano-Systems Targeting Heterogeneous Cancer Cells for Therapeutics and Biomarker Detection.

Cancer heterogeneity plays a vital part in cancer resistance and metastasis. To provide a reliable approach to exert a therapy action and evaluate its efficiency in heterogeneous cancer cells, a multiple targeting delivery vector composed of histone encapsulating the therapeutic or diagnostic agent, hyaluronic acid targeting CD44 overexpressed in stem tumor cells, SYL3C aptamer targeting epithelial cell adhesion molecule (EpCAM) overexpressed in epithelial cancer cells, and CL4 aptamer targeting epidermal growth factor receptor (EGFR) overexpressed in mesenchymal cancer cells, is developed. The vector can efficiently target different cancer cells and circulating tumor cells (CTCs) in the peripheral blood of patients for mucin 1 (MUC1) knockout. Furthermore, the multiple targeting vector can be used to co-encapsulate three types of molecular beacons for probing various mRNA biomarkers at single-cell resolution after genome editing. This study provides an efficient approach for exerting therapeutic actions in heterogeneous cancer cells and assessing the therapeutic efficacy by detection of cancer biomarkers via liquid biopsy.

A Multifunctional Delivery System for Remodulating Cell Behaviors of Circulating Malignant Cells to Prevent Cell Fusion.

Cell fusion plays a critical role in cancer progression and metastasis. However, effective modulation of the cell fusion behavior and timely evaluation on the cell fusion to provide accurate information for personalized therapy are facing challenges. Here, it demonstrates that the cancer cell fusion behavior can be efficiently modulated and precisely detected through employing a multifunctional delivery vector to realize cancer targeting delivery of a genome editing plasmid and a molecular beacon-based AND logic gate. The multifunctional delivery vector decorated by AS1411 conjugated hyaluronic acid and NLS-GE11 peptide conjugated hyaluronic acid can specifically target circulating malignant cells (CMCs) of cancer patients to deliver the genome editing plasmid for epidermal growth factor receptor (EGFR) knockout. The cell fusion between CMCs and endothelial cells can be detected by the AND logic gate delivered by the multifunctional vector. After EGFR knockout, the edited CMCs exhibit dramatically inhibited cell fusion capability, while unedited CMCs can easily fuse with human umbilical vein endothelial cells (HUVEC) to form hybrid cells. This study provides a new therapeutic strategy for preventing cancer progression and a reliable tool for evaluating cancer cell fusion for precise personalized therapy.

Synthesis of biodegradable and electroactive tetraaniline grafted poly(ester amide) copolymers for bone tissue engineering.

Biodegradable poly(ester amide)s have recently been used as biomaterials due to their desirable chemical and biological characteristics as well as their mechanical properties, which are amendable for material processing. In this study, electroactive tetraaniline (TA) grafted poly(ester amide)s were successfully synthesized and characterized. The poly(ester amide)s-graft-tetraaniline copolymers (PEA-g-TA) exhibited good electroactivity, mechanical properties, and biodegradability. The biocompatibility of the PEA-g-TA copolymers in vitro was systematically studied, which demonstrated that they were nontoxic and led to favorable adhesion and proliferation of mouse preosteoblastic MC3T3-E1 cells. Moreover, the PEA-g-TA copolymers stimulated by pulsed electrical signal could serve to promote the differentiation of MC3T3-E1 cells compared with TCPs. Hence, the biodegradable and electroactive PEA-g-TA copolymers possessed the properties in favor of the long-time potential application in vivo (electrical stimulation directly to the desired area) as bone repair scaffold materials in tissue engineering.

Urban hydrological responses to climate change and urbanization in cold climates.

This study explores hydrological response of urban catchment in Southern Finland to climate change and urbanization. Process-based urban hydrological modelling and statistical analysis are applied to various urbanization and climate scenarios. Future changes in precipitation and temperature under Representative Concentration Pathways 4.5 and 8.5 (RCP4.5 and RCP8.5, respectively) clearly influence urban streamflow all year-round. We found snowpack shrinks during 2061 to 2090, snowmelt becomes earlier and the amount of melted runoff is reduced under both climate scenarios. The most significant runoff increase occurs in winter with the growth rates of 79% and 127%, respectively. It is also found that the dominant portion of urban streamflow shifts from summer to autumn in the future under both RCP4.5 and RCP8.5. Results indicate that urbanization has direct impact on hydrological response due to the change of imperviousness, but climate change will have more significant impact on seasonal distribution of urban streamflow. Additionally, urbanization impacts shrink monthly streamflow differences along with climate change.