Acidity-unlocked glucose oxidase as drug vector to boost intratumor copper homeostatic imbalance-enhanced cuproptosis for metastasis inhibition and anti-tumor immunity.

As one of the key tools of biocatalysis, natural enzymes have received extensive attention due to their unique activity. However, the non-selective catalysis and early leakage induced by delivery dependency of natural enzymes can cause side effects on normal tissues. Moreover, although cuproptosis is an emerging tumor-inhibiting programmed cell death, the occurrence of cuproptosis leads to high expression of Cu-dependent lysyl oxidase-like 2 (LOXL2), which promotes tumor metastasis.

The efferocytosis dilemma: how neutrophil extracellular traps and PI3K/Rac1 complicate diabetic wound healing.

Aims/hypothesis: The resolution of apoptotic cells (ACs) is crucial for wound healing and tissue remodeling and is often impaired by persistent inflammation. This study aimed to elucidate the impact of neutrophil extracellular traps (NETs) on diabetic wound healing by targeting the phosphoinositide 3-kinase/Ras-related C3 botulinum toxin substrate 1 (PI3K/Rac1) signaling pathway, which is pivotal for macrophage efferocytosis.

Methods: A streptozotocin-induced diabetic mouse model was used to assess the impact of NETs on efferocytosis in vivo.

Inflammatory memory-activated biomimetic nanovesicles regulate neutrophil plasticity and metabolic reprogramming for rapid diabetic wound healing via targeting miR-193a-5p/TLR4/JNK/P38 MAPK pathways.

Diabetic wound therapy faces significant challenges due to the complexity of the wound microenvironment, especially dysregulated immune cell responses and persistent pro-inflammatory sate. Targeting immune cells to reverse pathological wound conditions has increasingly become a promising strategy to promote diabetic wound healing. It has been reported that prolonged memory to acute inflammation sensitizes epidermal stem cells (EpSCs) to tissue damage.

An Asymmetric Bacterial Cellulose Membrane Incorporating CuPt Nanozymes and Curcumin for Accelerating Wound Healing.

Damaged skin compromises its ability to effectively prevent the invasion of harmful bacteria into the tissue, leading to bacterial infection of the wound and hindering the healing process. To address this challenge, we have developed a multifunctional asymmetric wound dressing (CuPt-Cur-ABC) that effectively addresses the lack of bactericidal activity and the release of active ingredients in conventional bacterial cellulose (BC), which can be employed to create a barrier of defense between the wound and its surrounding environment. Compared with BC, asymmetric bacterial cellulose (ABC) used starch as a pore-causing agent, forming holes of different sizes at the top and bottom, which enhanced the ability of ABC to load and moderate-release drugs.

The effect of sarcopenic obesity on glycaemic status based on fasting plasma glucose and glycated haemoglobin: A prospective cohort study.

Aim: To investigate the effect of sarcopenic obesity on the progression of glycaemic status in middle-aged and older adults without diabetes.

Materials And Methods: This research involved 4637 participants without diabetes from the China Health and Retirement Longitudinal Study 2011-2015. Sarcopenic obesity at baseline was evaluated based on the Asian Working Group for Sarcopenia 2019 criteria.

Multifunctional Copper-Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy.

The overexpression of polyamines in tumor cells contributes to the establishment of immunosuppressive microenvironment and facilitates tumor growth. Here, it have ingeniously designed multifunctional copper-piceatannol/HA nanopills (Cu-Pic/HA NPs) that effectively cause total intracellular polyamines depletion by inhibiting polyamines synthesis, depleting intracellular polyamines, and impairing polyamines uptake, resulting in enhanced pyroptosis and cuproptosis, thus activating a powerful immune response to achieve anti-tumor therapy. Mitochondrial dysfunction resulting from overall intracellular polyamines depletion not only leads to the surge of copper ions in mitochondria, thereby causing the aggregation of toxic proteins to induce cuproptosis, but also triggers the accumulation of reactive oxygen species (ROS) within mitochondria, which further upregulates the expression of zDHHC5 and zDHHC9 to promote the palmitoylation of gasdermin D (GSDMD) and GSDMD-N, ultimately inducing enhanced pyroptosis.

Machine learning assisted designing of conjugated organic chromophores, light absorption, and emission behavior prediction.

Organic materials have several important characteristics that make them suitable for use in optoelectronics and optical signal processing applications. For absorption and emission maxima, the stabilities and photoactivities of conjugated organic chromophores can be tailored by selecting a suitable parent structure and incorporating substituents that predictably change the optical characteristics. However, a high-throughput design of efficient conjugated organic chromophores without using trial-and-error experimental approaches is required.

Fasting-Mimicking Diet Facilitates Anti-tumor Therapeutic Effects by Nutrient-Sensitive Nanocomposites.

Cancer cells support their uncontrolled proliferation primarily by regulating energy metabolism. Inhibiting tumor growth by blocking the supply of nutrients is an effective treatment strategy. Fasting-mimicking diet (FMD), as a low-calorie, low-protein, low-sugar, high-fat diet, can effectively reduce the nutrient supply to tumor cells.

"Three Musketeers" Enhances Photodynamic Effects by Reducing Tumor Reactive Oxygen Species Resistance.

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) has been widely used in the treatment of a variety of tumors. Compared with other therapeutic methods, this treatment has the advantages of high efficiency, strong penetration, and controllable treatment range. PDT kills tumors by generating a large amount of reactive oxygen species (ROS), which causes oxidative stress in the tumor.

Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy.

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME.

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing.

Background: Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles in angiogenesis and tissue repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, their exact mechanisms of action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes.

Tumor Microenvironment-Specific Driven Nanoagents for Synergistic Mitochondria Damage-Related Immunogenic Cell Death and Alleviated Immunosuppression.

Despite significant breakthroughs in immunotherapy, the limitations of inadequate immune stimulation and stubborn immune resistance continue to present opportunities and challenges. Therefore, a two-pronged approach, encompassing the activation of immunogenic cell death (ICD) and blocking the indoleamine 2,3-dioxygenase (IDO)-mediated pathway, is devised to elicit systemic anti-tumor immunity and alleviate immunosuppression. Herein, a tumor microenvironment (TME)-specific driven nanoagent is composed of a tetrasulfide bond-bridged mesoporous silica layer (MON) coated up-conversion nanoparticles as a nano-carrier, combines Fe, curcumin, and indoximod for operating chemodynamic therapy/chemotherapy/immunotherapy.

Near-Infrared Light-Triggered Thermoresponsive Pyroptosis System for Synergistic Tumor Immunotherapy.

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light-triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as Pt/GOx) are prepared as the mild-temperature triggered pyroptosis inducer.

Data mining and library generation to search electron-rich and electron-deficient building blocks for the designing of polymers for photoacoustic imaging.

Photoacoustic imaging is a good method for biological imaging, for this purpose, materials with strong near infrared (NIR) absorbance are required. In the present study, machine learning models are used to predict the light absorption behavior of polymers. Molecular descriptors are utilized to train a variety of machine learning models.

Photothermal-Enhanced Dual Inhibition of Lactate/Kynurenine Metabolism for Promoting Tumor Immunotherapy.

Traditionally referred to as "metabolic junk", lactate has now been recognized as essential "energy currency" and crucial "messenger" that contributes to tumor evolution, immunosuppression, etc., thus presenting a promising strategy for antitumor interventions. Similarly, kynurenine (Kyn) also exerts an immunosuppressive function, thereby significantly compromising the effectiveness of immunotherapy.

Rationally Integrated Precise ER-Targeted and Oxygen-Compensated Photodynamic Immunostimulant for Immunogenicity-Boosted Tumor Therapy.

Notwithstanding that immunotherapy has made eminent clinical breakthroughs, activating the immunogenicity and breaking the immunosuppressive tumor microenvironment (ITME) remains tempting yet challenging. Herein, a customized-designed immunostimulant is engineered for attenuating ITME and eliciting an immune response to address this challenge head-on. This immunostimulant is equipped with dual silica layers coated upconversion nanoparticles (UCNPs) as nanocarriers modified with endoplasmic reticulum (ER)-targeted molecular N-p-Tosylglycine, in which the dense silica for chlorin e6 (Ce6) and the glutathione (GSH)-responsive degradable silica for loading resveratrol (RES) - (UCSMR ).

Construction of mPt/ICG-αA nanoparticles with enhanced phototherapeutic activities for multidrug-resistant bacterial eradication and wound healing.

The emergence of multidrug-resistant (MDR) bacterial infections calls for novel strategies for effective bacterial inhibition and wound healing. Phototherapeutic approaches are promising in treating bacterial infection because of their high efficiency, noninvasiveness, and few side effects; however, their antibacterial effect is limited by the formation of biofilms in wounds. Herein, we report novel composite nanoparticles (mPt/ICG-αA NPs) combining mesoporous platinum (mPt) nanoparticles, indocyanine green (ICG) and α-amylase (αA) for combating MDR bacteria and treating wound infection, which integrates a triple bacterial inhibition mechanism arising from the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and α-amylase enzymatic activities.

Novel PdPtCu Nanozymes for Reprogramming Tumor Microenvironment to Boost Immunotherapy Through Endoplasmic Reticulum Stress and Blocking IDO-Mediated Immune Escape.

Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting tumor growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCT ) is prepared to boost immunotherapy. First, PNBCT has three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), and peroxidase (POD)-like activities, which can reshape the TME.

Preliminary study based on methylation and transcriptome gene sequencing of lncRNAs and immune infiltration in hypopharyngeal carcinoma.

Background: Hypopharyngeal squamous cell cancer (HSCC) is one of the most malignant tumors of the head and neck. It is not easy to detect in the early stage due to its hidden location; thus, lymph node metastasis is highly likely at diagnosis, leading to a poor prognosis. It is believed that epigenetic modification is related to cancer invasion and metastasis.

PtBi-β-CD-Ce6 Nanozyme for Combined Trimodal Imaging-Guided Photodynamic Therapy and NIR-II Responsive Photothermal Therapy.

Combined photothermal/photodynamic therapy is a promising strategy to achieve an enhanced anticancer effect. However, hypoxia is one of the representative characteristics of the microenvironment of solid tumors, which not only attenuates the therapeutic effects but also promotes tumor invasion and metastasis. Herein, a PtBi-β-CD-Ce6 nanoplatform for the generation of sustained O was constructed for more effective tumor therapy.

Insight into the photoelectrical properties of metal adsorption on a two-dimensional organic-inorganic hybrid perovskite surface: theoretical and experimental research.

In order to study the photoelectric properties of the adsorption of different metal atoms on a two-dimensional (2D) perovskite surface, in this article, we built many models of Ag, Au, and Bi atoms adsorbed on 2D perovskite. We studied the rules influencing 2D perovskite adsorbing metal atoms with different values (the value is the number of inorganic layers of 2D perovskite; here = 1, 2, and 3). Based on = 2 2D perovskite, we successively used Ag, Au, and Bi metal atoms to adsorb on the 2D perovskite surface.