Ligand-enabled ruthenium-catalyzed meta-C-H alkylation of (hetero)aromatic carboxylic acids.

Carboxylates are ideal directing groups because they are widely available, readily cleavable and excellent linchpins for diverse follow-up reactions. However, their use in meta-selective C-H functionalizations remains a substantial unmet catalytic challenge. Herein, we report the ruthenium-catalyzed meta-C-H alkylation of aromatic carboxylic acids with various functionalized alkyl halides. A bidentate N-ligand increases the electron density at the metal center of ortho-benzoate ruthenacycles to the extent that single-electron reductions of alkyl halides can take place. The subsequent addition of alkyl radicals is exclusively directed to the position para to the CAr-Ru bond, i.e., meta to the carboxylate group. The resulting catalytic meta-C-H alkylation extends to a wide range of (hetero)aromatic carboxylic acids including benzofused five-membered ring heteroarenes but no pyridine derivatives in combination with secondary/tertiary alkyl halides, including fluorinated derivatives. It also allows site-selective C5-H alkylation of 1-naphthoic acids. The products are shown to be synthetic hubs en route to meta-alkylated aryl ketones, nitriles, amides, esters and other functionalized products.

Multifunctional Therapeutic Nanodiamond Hydrogels for Infected-Wound Healing and Cancer Therapy.

Wound infection and tumor recurrence are the two main threats to cancer patients after surgery. Although researchers have developed new treatment systems to address the two significant challenges simultaneously, the potential side effects of the heavy-metal-ion-based treatment systems still severely limit their widespread application in therapy. In addition, the wounds from tumor removal compared with general operative wounds are more complex. The tumor wounds mainly exhibit more hemorrhage, larger trauma area, greater vulnerability to bacterial infection, and residual tumor cells. Therefore, a multifunctional treatment platform is urgently needed to integrate rapid hemostasis, sterilization, wound healing promotion, and antitumor functions. In this work, nanodiamonds (NDs), a material that has been well proven to have excellent biocompatibility, are added into a solution of acrylic-grafted chitosan (CEC) and oxidized hyaluronic acid (OHA) to construct a multifunctional treatment platform (CEC-OHA-NDs). The hydrogels exhibit rapid hemostasis, a wound-healing-promoting effect, excellent self-healing, and injectable abilities. Moreover, CEC-OHA-NDs can effectively eliminate bacteria and inhibit tumor proliferation by the warm photothermal effect of NDs under tissue-penetrable near-infrared laser irradiation (NIR) without cytotoxicity. Consequently, we adopt a simple and convenient strategy to construct a multifunctional treatment platform using carbon-based nanomaterials with excellent biocompatibility to promote the healing of infected wounds and to inhibit tumor cell proliferation simultaneously.

Delocalization Engineering of Heme-Mimetic Artificial Enzymes for Augmented Reactive Oxygen Catalysis.

Developing artificial enzymes based on organic molecules or polymers for reactive oxygen species (ROS)-related catalysis has broad applicability. Herein, inspired by porphyrin-based heme mimics, we report the synthesis of polyphthalocyanine-based conjugated polymers (Fe-PPc-AE) as a new porphyrin-evolving structure to serve as efficient and versatile artificial enzymes for augmented reactive oxygen catalysis. Owing to the structural advantages, such as enhanced π-conjugation networks and π-electron delocalization, promoted electron transfer, and unique Fe-N coordination centers, Fe-PPc-AE showed more efficient ROS-production activity in terms of Vmax and turnover numbers as compared with porphyrin-based conjugated polymers (Fe-PPor-AE), which also surpassed reported state-of-the-art artificial enzymes in their activity. More interestingly, by changing the reaction medium and substrates, Fe-PPc-AE also revealed significantly improved activity and environmental adaptivity in many other ROS-related biocatalytic processes, validating the potential of Fe-PPc-AE to replace conventional (poly)porphyrin-based heme mimics for ROS-related catalysis, biosensors, or biotherapeutics. It is suggested that this study will offer essential guidance for designing artificial enzymes based on organic molecules or polymers.

Ruthenium-Catalyzed C-H Arylation of Aromatic Acids with ortho-Haloaniline To Access Phenanthridinones.

Phenanthridinone is a significant moiety in pharmaceutical and material science; thus, it is highly desirable to develop an efficient and robust method to construct phenanthridinone from readily available starting materials. Herein, we report a Ru-catalyzed C-H arylation of aromatic carboxylic acids with ortho-haloanilines, followed by intramolecular dehydration to afford phenanthridinones in high yields.

Effect of zwitterionic sulfobetaine incorporation on blood behaviours, phagocytosis, and in vivo biodistribution of pH-responsive micelles with positive charges.

pH-responsive micelles with positive charges are challenged by their significant effect on the cells/proteins and compromise their final fate due to electrostatic interactions. As one of the promising strategies, zwitterion incorporation in micelles has attracted considerable attention and displayed improved protein adsorption and blood circulation performances. However, previous reports in this field have been mostly limited in hemolysis for studying blood behaviour and lack a comprehensive understanding of their interactions with blood components. Herein, we present a prelimilary study on the effect of zwitterionic sulfobetaine incorporation on blood behaviour, phagocytosis, and in vivo biodistribution of pH-responsive micelles with positive charges. Amphiphilic triblock copolymers, namely poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-(N-(3-sulfopropyl-N-methacryloxyethy-N,N-diethylammonium betaine)) (PCL-PDEAPSx, x = 2, 6, 10), containing different numbers of sulfobetaine groups were synthesized through four steps to prepare the pH-responsive micelles with positive charges. The effect of the sulfobetaine incorporation displayed different profiles, e.g., the micelles had no effect on RBC aggregation, thrombin time (TT), and platelet aggregation, while the cytotoxicity, hemolysis, RBC deformability, activated partial thromboplastin time (APTT), prothrombin time (PT), platelet activation, protein (albumin, fibrinogen, plasma) adsorption, phagocytosis, and in vivo biodistribution decreased with the increase in the sulfobetaine number, in which the transition mainly occurred at a sulfobetaine/tertiary amine group ratio of 3/7-1/1 compared to that of the mPEG control. In addition, the micelles displayed a strong inhibitory effect on the intrinsic coagulation pathway, which was associated with a significant decrease in the coagulation factor activity. Based on these findings, the related mechanism is discussed and proposed, which can aid the rational design of pH-responsive micelles for improved therapeutics.

Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis.

Solar dermatitis, a form of acute radiation burn that affects the skin, results from overexposure to ultraviolet B (UVB) radiation in strong sunlight. Cell damage caused by the accumulation of reactive oxygen species (ROS) produced by UVB radiation plays an important role in UVB-induced inflammation in the skin. Here, for efficiently scavenging excess ROS, modulating the microenvironment, and alleviating solar dermatitis, a π-conjugated network polyphthalocyanine supporting a highly surface-exposed Ru active site-based artificial antioxidase (HSE-PPcRu) is designed and fabricated with excellent ROS-scavenging, antioxidant, and anti-inflammatory capabilities. In photodamaged human keratinocyte cells, HSE-PPcRu could modulate mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B signaling pathways, prevent DNA damage, suppress apoptosis, inhibit pro-inflammatory cytokine secretion, and alleviate cell damage. In vivo animal experiments reveal the higher antioxidant and anti-inflammatory efficacies of HSE-PPcRu by reversing the activation of p38 and c-Jun N-terminal kinase, inhibiting expression of cyclooxygenase-2, interleukin-6, interleukin-8, and tumor necrosis factor-α. This work not only provides an idea for alleviating solar dermatitis via catalytically scavenging ROS and modulating the microenvironment but also offers a strategy to design an intelligent conjugated network-based artificial antioxidase with a highly surface-exposed active site.

Effect of serum inflammatory factors in predicting co-infection with influenza viruses and Omicron.

OBJECTIVES: To identify the key differences in laboratory indicators between mono-infection and co-infection by influenza viruses and Omicron to facilitate timely adjustments in patient treatment strategies. METHODS: Prealbumin and C-reactive protein (CRP) levels were analyzed in 161 COVID-19 cases infected by SARS-CoV-2 (wild type), 299 cases infected by Omicron, 95 cases infected by influenza virus A/B (Flu A/B) and 133 co-infection cases infected with Flu A/B and Omicron. The receiver operating characteristic (ROC) curve and logistic regression equation were used to analyze the clinical predictive capacity of prealbumin and CRP in coinfected patients. RESULTS: The co-infected and wild-type infected patients had significantly different CRP and prealbumin levels compared to mono-infected patients with Omicron or Flu A/B (p < .001). The ROC curve results indicated that prealbumin was more efficient than CRP in identifying co-infection from Omicron (AUC: 0.867 vs. 0.724) or Flu A/B (AUC: 0.797 vs. 0.730), and joint prediction significantly improved the diagnostic ability to discriminate co-infection from mono-infection (AUC: 0.934 and 0.887). CONCLUSION: The findings suggest that prealbumin is a valuable indicator that can warn of co-infection and guide timely treatment decisions. Joint prediction may offer an even more effective diagnostic tool for discriminating co-infection from mono-infection.

Ultralow Ru Single Atoms Confined in Cerium Oxide Nanoglues for Highly-Sensitive and Robust H2 O2 -Related Biocatalytic Diagnosis.

Exploring highly efficient, portable, and robust biocatalysts is a great challenge in colorimetric biosensors. To overcome the challenging states in creating single-atom biocatalysts, such as insufficient activity and stability, here, this work has engineered a unique CeO2 support as nanoglue to tightly anchor the Ru single-atom sites (CeO2 -Ru) with strong electronic coupling for achieving highly sensitive and robust H2 O2 -related biocatalytic diagnosis. The morphology and chemical/electronic structure analysis demonstrates that the Ru atoms are well-dispersed on CeO2 surface to form high-density active sites. Benefiting from the unique structure, the prepared CeO2 -Ru exhibits outstanding peroxidase (POD) like catalytic activity and selectivity to H2 O2 . Steady-state kinetic study results show that the CeO2 -Ru presents the highest Vmax and turnover number than the state-of-the-art POD-like biocatalysts. Consequently, the CeO2 -Ru discloses a high efficiency, good selectivity, and robust stability in the colorimetric detection of L-cysteine, glucose, and uric acid. Notably, the limit of detection (LOD) can reach 0.176 × 10-3 m for the L-cysteine, 0.095 × 10-3 m for the glucose, and 0.088 × 10-3 m for the uric acid via cascade reaction. This work suggests that the proposed unique CeO2 nanoglue will offer a new path to create single-atom noble metal biocatalysts and take a step closer to future biotherapeutic and biocatalytic applications.

Mn-Oxygen Compounds Coordinated Ruthenium Sites with Deprotonated and Low Oxophilic Microenvironments for Membrane Electrolyzer-Based H2 -Production.

Among the platinum-group metals, ruthenium (Ru), with a low water dissociation energy, is considered a promising alternative to substitute Pt for catalyzing hydrogen evolution reaction (HER). However, optimizing the adsorption-desorption energies of H* and OH* intermediates on Ru catalytic sites is extremely desirable but remains challenging. Inspired by the natural catalytic characteristics of Mn-oxygen complex, this study reports to design Mn-oxygen compounds coordinated Ru sites (MOC-Ru) with deprotonated and low oxophilic microenvironments for modulating the adsorption-desorption of H* and OH* to promote HER kinetics. Benefiting from the unique advantages of MOC structures, including weakened HOH bond at interface, electron donation ability, and deprotonation capability, the MOC-Ru exhibits extremely low overpotential and ultralong stability in both acidic and alkaline electrolytes. Experimental observations and theoretical calculations elucidate that the MOC can accelerate water dissociation kinetics and promote OH* desorption in alkaline conditions and trigger the long-range H* spillover for H2 -release in acid conditions. The outstanding activity and stability of membrane electrolyzer display that the MOC-Ru catalyst holds great potential as cathode for H2 -production. This study provides essential insights into the crucial roles of deprotonated and low oxophilic microenvironments in HER catalysis and offers a new pathway to create an efficient water-splitting cathode.

Microenvironment Restruction of Emerging 2D Materials and their Roles in Therapeutic and Diagnostic Nano-Bio-Platforms.

Engineering advanced therapeutic and diagnostic nano-bio-platforms (NBPFs) have emerged as rapidly-developed pathways against a wide range of challenges in antitumor, antipathogen, tissue regeneration, bioimaging, and biosensing applications. Emerged 2D materials have attracted extensive scientific interest as fundamental building blocks or nanostructures among material scientists, chemists, biologists, and doctors due to their advantageous physicochemical and biological properties. This timely review provides a comprehensive summary of creating advanced NBPFs via emerging 2D materials (2D-NBPFs) with unique insights into the corresponding molecularly restructured microenvironments and biofunctionalities. First, it is focused on an up-to-date overview of the synthetic strategies for designing 2D-NBPFs with a cross-comparison of their advantages and disadvantages. After that, the recent key achievements are summarized in tuning the biofunctionalities of 2D-NBPFs via molecularly programmed microenvironments, including physiological stability, biocompatibility, bio-adhesiveness, specific binding to pathogens, broad-spectrum pathogen inhibitors, stimuli-responsive systems, and enzyme-mimetics. Moreover, the representative therapeutic and diagnostic applications of 2D-NBPFs are also discussed with detailed disclosure of their critical design principles and parameters. Finally, current challenges and future research directions are also discussed. Overall, this review will provide cutting-edge and multidisciplinary guidance for accelerating future developments and therapeutic/diagnostic applications of 2D-NBPFs.

Manganese-Based Antioxidase-Inspired Biocatalysts with Axial Mn-N5 Sites and 2D d-π-Conjugated Networks for Rescuing Stem Cell Fate.

Constructing highly effective biocatalysts with controllable coordination geometry for eliminating reactive oxygen species (ROS) to address the current bottlenecks in stem-cell-based therapeutics remains challenging. Herein, inspired by the coordination structure of manganese-based antioxidase, we report a manganese-coordinated polyphthalocyanine-based biocatalyst (Mn-PcBC) with axial Mn-N5 sites and 2D d-π-conjugated networks that serves as an artificial antioxidase to rescue stem cell fate. Owing to the unique chemical and electronic structures, Mn-PcBC displays efficient, multifaceted, and robust ROS-scavenging activities, including elimination of H2 O2 and O2 ⋅- . Consequently, Mn-PcBC efficiently rescues the bioactivity and functionality of stem cells in high-ROS-level microenvironments by protecting the transcription of osteogenesis-related genes. This study offers essential insight into the crucial functions of axially coordinated Mn-N5 sites in ROS scavenging and suggests new strategies to create efficient artificial antioxidases for stem-cell therapies.

Metal Alloys-Structured Electrocatalysts: Metal-Metal Interactions, Coordination Microenvironments, and Structural Property-Reactivity Relationships.

Metal alloys-structured electrocatalysts (MAECs) have made essential contributions to accelerating the practical applications of electrocatalytic devices in renewable energy systems. However, due to the complex atomic structures, varied electronic states, and abundant supports, precisely decoding the metal-metal interactions and structure-activity relationships of MAECs still confronts great challenges, which is critical to direct the future engineering and optimization of MAECs. Here, this timely review comprehensively summarizes the latest advances in creating the MAECs, including the metal-metal interactions, coordination microenvironments, and structure-activity relationships. First, the fundamental classification, design, characterization, and structural reconstruction of MAECs are outlined. Then, the electrocatalytic merits and modulation strategies of recent breakthroughs for noble and non-noble metal-structured MAECs are thoroughly discussed, such as solid solution alloys, intermetallic alloys, and single-atom alloys. Particularly, unique insights into the bond interactions, theoretical understanding, and operando techniques for mechanism disclosure are given. Thereafter, the current states of diverse MAECs with a unique focus on structural property-reactivity relationships, reaction pathways, and performance comparisons are discussed. Finally, the future challenges and perspectives for MAECs are systematically discussed. It is believed that this comprehensive review can offer a substantial impact on stimulating the widespread utilization of metal alloys-structured materials in electrocatalysis.

Semiconducting Titanate Supported Ruthenium Clusterzymes for Ultrasound-Amplified Biocatalytic Tumor Nanotherapies.

The external-stimulation-induced reactive-oxygen-species (ROS) generation has attracted increasing attention in therapeutics for malignant tumors. However, engineering a nanoplatform that integrates with efficient biocatalytic ROS generation, ultrasound-amplified ROS production, and simultaneous relief of tumor hypoxia is still a great challenge. Here, we create new semiconducting titanate-supported Ru clusterzymes (RuNC/BTO) for ultrasound-amplified biocatalytic tumor nanotherapies. The morphology and chemical/electronic structure analysis prove that the biocatalyst consists of Ru nanoclusters that are tightly stabilized by Ru-O coordination on BaTiO3 . The peroxidase (POD)- and halogenperoxidase-like biocatalysis reveals that the RuNC/BTO can produce abundant •O2 - radicals. Notably, the RuNC/BTO exhibits the highest turnover number (63.29 × 10-3 s-1 ) among the state-of-the-art POD-mimics. Moreover, the catalase-like activity of the RuNC/BTO facilitates the decomposition of H2 O2 to produce O2 for relieving the hypoxia of the tumor and amplifying the ROS level via ultrasound irradiation. Finally, the systematic cellular and animal experiments have validated that the multi-modal strategy presents superior tumor cell-killing effects and suppression abilities. We believe that this work will offer an effective clusterzyme that can adapt to the tumor microenvironment-specific catalytic therapy and also provide a new pathway for engineering high-performance ROS production materials across broad therapeutics and biomedical fields.

Electronic Structure-Dependent Water-Dissociation Pathways of Ruthenium-Based Catalysts in Alkaline H2 -Evolution.

Ruthenium (Ru)-based catalysts have displayed compelling hydrogen evolution activities, which hold the promising potential to substitute platinum in alkaline H2 -evolution. In the challenging alkaline electrolytes, the water-dissociation process involves multistep reactions, while the profound origin and intrinsic factors of diverse Ru species on water-dissociation pathways and reaction principles remain ambiguous. Here the fundamental origin of water-dissociation pathways of Ru-based catalysts in alkaline media to be from their unique electronic structures in complex coordination environments are disclosed. These theoretical results validate that the modulated electronic structures with delocalization-localization coexistence at their boundaries between the Ru nanocluster and single-atom site have a profound influence on water-dissociation pathways, which push H2 O* migration and binding orientation during the splitting process, thus enhancing the dissociation kinetics. By creating Ru catalysts with well-defined nanocluster, single-atom site, and also complex site, the electrocatalytic data shows that both the nanocluster and single-atom play essential roles in water-dissociation, while the complex site possesses synergistically enhanced roles in alkaline electrolytes. This study discloses a new electronic structure-dependent water-dissociation pathway and reaction principle in Ru-based catalysts, thus offering new inspiration to design efficient and durable catalysts for the practical production of H2 in alkaline electrolytes.

Electrocatalytic Porphyrin/Phthalocyanine-Based Organic Frameworks: Building Blocks, Coordination Microenvironments, Structure-Performance Relationships.

Metal-porphyrins or metal-phthalocyanines-based organic frameworks (POFs), an emerging family of metal-N-C materials, have attracted widespread interest for application in electrocatalysis due to their unique metal-N4 coordination structure, high conjugated π-electron system, tunable components, and chemical stability. The key challenges of POFs as high-performance electrocatalysts are the need for rational design for porphyrins/phthalocyanines building blocks and an in-depth understanding of structure-activity relationships. Herein, the synthesis methods, the catalytic activity modulation principles, and the electrocatalytic behaviors of 2D/3D POFs are summarized. Notably, detailed pathways are given for modulating the intrinsic activity of the M-N4 site by the microenvironments, including central metal ions, substituent groups, and heteroatom dopants. Meanwhile, the topology tuning and hybrid system, which affect the conjugation network or conductivity of POFs, are also considered. Furthermore, the representative electrocatalytic applications of structured POFs in efficient and environmental-friendly energy conversion areas, such as carbon dioxide reduction reaction, oxygen reduction reaction, and water splitting are briefly discussed. Overall, this comprehensive review focusing on the frontier will provide multidisciplinary and multi-perspective guidance for the subsequent experimental and theoretical progress of POFs and reveal their key challenges and application prospects in future electrocatalytic energy conversion systems.

Metal-oxo Cluster Mediated Atomic Rh with High Accessibility for Efficient Hydrogen Evolution.

Achieving single-atom catalysts (SACs) with high metal content and outstanding performance as well as robust stability is critically needed for clean and sustainable energy. However, most of the synthesized SACs are undesired on the loading content of the metal due to the anchored metals and the supports as well as the synthesizing methods. Herein, a Rh-SAC with high accessibility by loading it on the metal nodes of metal-porphyrin-based PCN MOFs (PCN-224) as supporting material is reported. Significantly, the PCN-Rh15.9 /KB catalyst with a high Rh content of 15.9 wt% exhibits excellent hydrogen evolution activity with a low overpotential of 25 mV at a current density of 10 mA cm-2 and a mass activity of 7.7 A mg-1 Rh at overpotential of 150 mV, which is much better than that of the commercial Rh/C. Various characterizations reveal the Rh species is stabilized by the metal nodes bearing -O/OHx in MOFs, which is of importance for the high loading amount and the good activity. This work establishes an efficient approach to synthesize high content SACs on the nodes of MOFs for wide catalyst design.

Modulating Electronic Environment of Ru Nanoclusters via Local Charge Transfer for Accelerating Alkaline Water Electrolysis.

Compared to platinum catalysts, ruthenium (Ru) is disclosed as a promising alternative for alkaline water electrolysis due to its similar hydrogen adsorption energy and relatively lower water dissociation barrier. However, in the challenging alkaline media, the dissatisfied Volmer step during water dissociation of Ru metal prohibits its practical applications. Here, a new pathway to modulate the electronic environment of Ru catalysts via a local charge transfer strategy for tuning the water dissociation kinetics and accelerating the alkaline water electrolysis is proposed. The obtained catalysts are engineered by assembling and subsequently pyrolyzing the layer-stacked and 2D porphyrin-based Ru-N coordination polymers on nanocarbon supports. Benefiting from the well-defined Ru nanocluster-Nx -coordination bonds (Runc -Nx ), unique electronic environments, and local charge transfer properties, the catalysts exhibit the exceptional activity of 17 mV overpotential at 10 mA cm-2 and robust stability in water, which is more efficient than state-of-the-art Ru catalysts. The theoretical calculation suggests that the Runc -Nx sites enhance the nucleophilic attack of water and weaken the HOH bond. This study manifests that tailoring the bond environments of Ru clusters can significantly modulate their intrinsic catalytic activities and stabilities, which may open new avenues for developing high-active and durable catalysts for water electrolysis.

Interpretable machine learning for 28-day all-cause in-hospital mortality prediction in critically ill patients with heart failure combined with hypertension: A retrospective cohort study based on medical information mart for intensive care database-IV and eICU databases.

Background: Heart failure (HF) combined with hypertension is an extremely important cause of in-hospital mortality, especially for the intensive care unit (ICU) patients. However, under intense working pressure, the medical staff are easily overwhelmed by the large number of clinical signals generated in the ICU, which may lead to treatment delay, sub-optimal care, or even wrong clinical decisions. Individual risk stratification is an essential strategy for managing ICU patients with HF combined with hypertension. Artificial intelligence, especially machine learning (ML), can develop superior models to predict the prognosis of these patients. This study aimed to develop a machine learning method to predict the 28-day mortality for ICU patients with HF combined with hypertension. Methods: We enrolled all critically ill patients with HF combined with hypertension in the Medical Information Mart for IntensiveCare Database-IV (MIMIC-IV, v.1.4) and the eICU Collaborative Research Database (eICU-CRD) from 2008 to 2019. Subsequently, MIMIC-IV was divided into training cohort and testing cohort in an 8:2 ratio, and eICU-CRD was designated as the external validation cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression with internal tenfold cross-validation was used for data dimension reduction and identifying the most valuable predictive features for 28-day mortality. Based on its accuracy and area under the curve (AUC), the best model in the validation cohort was selected. In addition, we utilized the Shapley Additive Explanations (SHAP) method to highlight the importance of model features, analyze the impact of individual features on model output, and visualize an individual's Shapley values. Results: A total of 3,458 and 6582 patients with HF combined with hypertension in MIMIC-IV and eICU-CRD were included. The patients, including 1,756 males, had a median (Q1, Q3) age of 75 (65, 84) years. After selection, 22 out of a total of 58 clinical parameters were extracted to develop the machine-learning models. Among four constructed models, the Neural Networks (NN) model performed the best predictive performance with an AUC of 0.764 and 0.674 in the test cohort and external validation cohort, respectively. In addition, a simplified model including seven variables was built based on NN, which also had good predictive performance (AUC: 0.741). Feature importance analysis showed that age, mechanical ventilation (MECHVENT), chloride, bun, anion gap, paraplegia, rdw (RDW), hyperlipidemia, peripheral capillary oxygen saturation (SpO2), respiratory rate, cerebrovascular disease, heart rate, white blood cell (WBC), international normalized ratio (INR), mean corpuscular hemoglobin concentration (MCHC), glucose, AIDS, mean corpuscular volume (MCV), N-terminal pro-brain natriuretic peptide (Npro. BNP), calcium, renal replacement therapy (RRT), and partial thromboplastin time (PTT) were the top 22 features of the NN model with the greatest impact. Finally, after hyperparameter optimization, SHAP plots were employed to make the NN-based model interpretable with an analytical description of how the constructed model visualizes the prediction of death. Conclusion: We developed a predictive model to predict the 28-day mortality for ICU patients with HF combined with hypertension, which proved superior to the traditional logistic regression analysis. The SHAP method enables machine learning models to be more interpretable, thereby helping clinicians to better understand the reasoning behind the outcome and assess in-hospital outcomes for critically ill patients.

CuS-PNIPAm nanoparticles with the ability to initiatively capture bacteria for photothermal treatment of infected skin.

Copper sulfide nanoparticles (CuS NPs) have shown great potential in various application fields, especially in biomedical engineering fields. CuS NPs, with the ability to actively capture and kill bacteria and without the worry of biocompatibility, will greatly expand their applications. Herein, a four-arm star thermo-sensitive polyisopropylacrylamide (4sPNIPAm) was used to modify CuS NPs (CuS-PNIPAm NPs). The obtained NPs displayed the controlled release of copper ions and higher photothermal conversion ability in comparison with contrast materials CuS-PEG NPs and CuS NPs. Aggregation of CuS-PNIPAm NPs at above 34°C resulted in capturing bacteria by forming the aggregates of NPs-bacteria. Both Staphylococcus aureus and Escherichia coli co-cultured with CuS-PNIPAm NPs were completely killed upon near-infrared irradiation in minutes. Furthermore, CuS-PNIPAm NPs were verified to be a photothermal agent without toxic effect. In in vivo experiment, the NPs effectively killed the bacteria in the wound and accelerated the process of wound repairment. Overall, photothermal treatment by CuS-PNIPAm NPs demonstrates the ability to actively capture and kill bacteria, and has a potential in the treatment of infected skin and the regeneration of skin tissues. The therapy will exert a far-reaching impact on the regeneration of stubborn chronic wounds.

π-Conjugated Copper Phthalocyanine Nanoparticles as Highly Sensitive Sensor for Colorimetric Detection of Biomarkers.

Though numerous nanomaterials with enzyme-like activities have been utilized as probes and sensors for detecting biological molecules, it is still challenging to construct highly sensitive detectors for biomarkers using polymeric materials. Benefiting from the π-d delocalization effect of electrons, excellent metal-chelating property, high electron transferability, and good chemical stability of π-conjugated phthalocyanine, the design of the copper phthalocyanine-based conjugated polymer nanoparticles (Cu-PcCP NPs) as a colorimetric sensor for a variety of biomarkers is reported. The Cu-PcCP NPs are synthesized through a simple microwave-assisted polymerization, and their chemical structures are thoroughly characterized. The colorimetric results of Cu-PcCP NPs demonstrate excellent peroxidase-like detecting activity and also great substrate selectivity than most of the reported Cu-based nanomaterials. The Cu-PcCP NPs can achieve a detection limit of 4.88 µM for the H2 O2 , 4.27 µM for the L-cysteine, and 21.10 µM for the glucose via a cascade catalytic system, which shows comparable detecting sensitivity as that of many earlier reported enzyme-like nanomaterials. Moreover, Cu-PcCP NPs present remarkable resistance to harsh conditions, including high temperature, low pH, and excessive salts. These highly specific π-conjugated copper-phthalocyanine nanoparticles not only overcome the current limitation of polymeric material-based sensors but also provide a new direction for designing next-generation enzyme-like nanomaterial-based colorimetric biosensors.