NIR light-activated nanocomposites combat biofilm formation and enhance antibacterial efficacy for improved wound healing.

Nanoparticle-based therapies are emerging as a pivotal frontier in biomedical research, showing their potential in combating infections and facilitating wound recovery. Herein, selenium-tellurium dopped copper oxide nanoparticles (SeTe-CuO NPs) with dual photodynamic and photothermal properties were synthesized, presenting an efficient strategy for combating bacterial infections. In vitro evaluations revealed robust antibacterial activity of SeTe-CuO NPs, achieving up to 99% eradication of bacteria and significant biofilm inhibition upon near-infrared (NIR) irradiation. Moreover, in vivo studies demonstrated accelerated wound closure upon treatment with NIR-activated SeTe-CuO NPs, demonstrating their efficacy in promoting wound healing. Furthermore, SeTe-CuO NPs exhibited rapid bacterial clearance within wounds, offering a promising solution for wound care. Overall, this versatile platform holds great promise for combating multidrug-resistant bacteria and advancing therapeutic interventions in wound management.

Glutathione-Scavenging Celastrol-Cu Nanoparticles Induce Self-Amplified Cuproptosis for Augmented Cancer Immunotherapy.

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis is highly dependent on intracellular copper accumulation and counteracted by a high level of glutathione (GSH) in tumor cells. Here, this work develops a self-amplified cuproptosis nanoparticles (Cel-Cu NP) using celastrol (Cel), a natural product isolated from medical plant. In Cel-Cu NP, Cel serves as a versatile copper ionophore, exhibiting an ideal coordination capacity toward copper ions without compromising the cuproptosis induction. Notably, Cel can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, this self-amplified cuproptosis further activates immunogenic cell death (ICD) to elicit robust immune response. Combining with immune checkpoint blockade, Cel-Cu NP effectively eradicates metastatic tumors in a mouse lung metastasis model. This study provides an efficient nanomedicine by inducing self-amplified cuproptosis for robust immunotherapy.

Untargeted Metabolome Analyses Revealed Potential Metabolic Mechanisms of Leymus chinensis in Response to Simulated Animal Feeding.

Leymus chinensis (Trin.) Tzvel., also known as the "Alkali Grass", is a major forage grass in the eastern and northeastern steppe vegetation in the Songnen Prairie. It is of great practical significance for grassland management to understand the influence of animal saliva on L. chinensis during animal feeding. In this study, we used clipping and daubing animal saliva to simulate responses to grazing by L. chinensis, and analyzed the physiological and metabolomic changes in response to simulated animal feeding. Results showed that the effects of animal saliva on physiological and metabolic processes of the treated plants produced a recovery phenomenon. Moreover, the effects of animal saliva produced a large number of differential metabolites related to several known metabolic pathways, among which the flavonoid biosynthesis pathway has undergone significant and persistent changes. We posit that the potential metabolic mechanisms of L. chinensis in response to simulated animal feeding are closely related to flavonoid biosynthesis.

Individual and family factors correlated with children's fruit consumption.

Background: Fruits are essential for health, yet their consumption in children is inadequate, with unclear influencing factors. Methods: A cross-sectional study was conducted among students in grades 3-12 in Beijing, China, from September 2020 to June 2021. Fruit consumption in children was surveyed using a self-administered food frequency questionnaire. Additionally, children's food and nutrition literacy and family food environments were assessed using the "Food and Nutrition Literacy Questionnaire for Chinese School-age Children" and the "Family Food Environment Questionnaire for Chinese School-age Children," respectively. Results: Out of 10,000 participating children, 62.5% consumed fruit daily, with a lower frequency among boys (59.3%) compared to girls (65.8%), and among senior students (48.6%) compared to junior (63.6%) and primary students (71.2%). Fruit consumption was positively associated with other healthy foods (vegetables, whole grains, etc.) and negatively with unhealthy foods (sugared soft drinks). Children with higher food and nutrition literacy consumed fruits daily more frequently (82.4% vs. 59.9%, ORs = 2.438, 95%CI: 2.072-2.868). A significant positive correlation was found between children's fruit consumption and a healthy family food environment (66.4% vs. 50.2%, OR = 1.507, 95%CI: 1.363-1.667). Conclusion: The results indicate that individual food and nutrition literacy and family food environment are key positive predictors of children's fruit consumption. Future interventions should focus on educating children and encouraging parents to foster supportive family environments.

A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR-Light Triggered Hyperthermia.

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG-Mngel) formed by crosslinking sodium alginate (SA) with manganese-doped bioactive glass (BG-Mn) is developed as a versatile platform for anti-tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune-suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG-Mngel with anti-PD-1 antibody (α-PD-1) for the treatment of malignant melanoma, it shows enhanced anti-tumor immune response and long-term immune memory response. Remarkably, BG-Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

A Polyplatin with Hands-Holding Near-Infrared-II Fluorophores and Prodrugs at a Precise Ratio for Tracking Drug Fate with Realtime Readout and Treatment Feedback.

The in vivo fate of chemotherapeutic drugs plays a vital role in understanding the therapeutic outcome, side effects, and the mechanism. However, the lack of imaging abilities of drugs, tedious labeling processes, and premature leakage of imaging agents result in loss of fidelity between the drugs and imaging signals. Herein, an amphiphilic polymer is created by copolymerization of a near-infrared-II (NIR-II) fluorophore tracer (T) and an anticancer Pt(IV) prodrug (D) of cisplatin in a hand-holding manner into one polymer chain for the first time. The obtained PolyplatinDT is capable of delivering the drugs and the fluorophores concomitantly at a precise D/T ratio, thereby resulting in tracking the platinum drugs and even readout of them in real-time via NIR-II imaging. PolyplatinDT can self-assemble into nanoparticles, referred to as NanoplatinDT. Furthermore, a caspase-3 cleavable peptide that serves as an apoptosis reporter is attached to NanoplatinDT, resulting in NanoplatinDTR that are capable of simultaneously tracking platinum drugs and evaluating the therapeutic efficacy. Overall, it is reported here the design of the first theranostic polymer with anticancer drugs, drug tracers, and drug efficacy reporters that can work in concert to provide insight into the drug fate and mechanism of action.

Antibody-platinum (IV) prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma.

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.

Nanomedomics.

Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.

Dyeing of Tussah Silk with Reactive Dyes: Dye Selection, Dyeing Conditions, Dye Fixation Characteristics, and Comparison with Mulberry Silk.

Tussah silk is one of the most widely used wild silks. It is usually dyed with acid dyes, despite the shortcoming of poor wet fastness. Reactive dyeing is a good solution to this problem. In our work, sulfatoethylsulfone (SES), sulfatoethylsulfone/monochlorotriazine (SES/MCT), monochlorotriazine (MCT), and bis(monochlorotriazine) (Bis(MCT)) dyes were used to dye tussah silk. All of these dyes showed lower exhaustion and fixation on tussah silk than on mulberry silk under alkaline conditions. Among them, SES dyes were more applicable, with a fixation of 70-85% (at 4%owf dye) at 90 °C when using sodium bicarbonate as an alkali. SES dyes also showed a rapid fixation speed. The dyeing of tussah silk required lower sodium bicarbonate dosage, the use of more neutral electrolytes, and a higher dye quantity to achieve deep effects compared to mulberry silk. Dyed tussah silk displayed lower apparent color depth and brilliance than dyed mulberry silk. The neutral boiling dyeing of tussah silk with SES dyes exhibited higher exhaustion, higher fixation (82-92% at 4%owf dye), and a slower fixation speed compared with alkaline dyeing. Furthermore, in this dyeing method, SES dyes showed higher and more efficient fixation on tussah silk than on mulberry silk. All dyed tussah silk had excellent color fastness to soaping.

Intergrating Hollow Multishelled Structure and High Entropy Engineering toward Enhanced Mechano-Electrochemical Properties in Lithium Battery.

Hollow multishelled structures (HoMSs) are attracting great interest in lithium-ion batteries as the conversion anodes, owing to their superior buffering effect and mechanical stability. Given the synthetic challenges, especially elemental diffusion barrier in the multimetal combinations, this complex structure design has been realized in low- and medium-entropy compounds so far. It means that poor reaction reversibility and low intrinsic conductivity remain largely unresolved. Here, a hollow multishelled (LiFeZnNiCoMn)3O4 high entropy oxide (HEO) is developed through integrating molecule and microstructure engineering. As expected, the HoMS design exhibits significant targeting functionality, yielding satisfactory structure and cycling stability. Meanwhile, the abundant oxygen defects and optimized electronic structure of HEO accelerate the lithiation kinetics, while the retention of the parent lattice matrix enables reversible lithium storage, which is validated by rigorous in situ tests and theoretical simulations. Benefiting from these combined properties, such hollow multishelled HEO anode can deliver a specific capacity of 967 mAh g-1 (89% capacity retention) after 500 cycles at 0.5 A g-1. The synergistic lattice and volume stability showcased in this work holds great promise in guiding the material innovations for the next-generation energy storage devices.

Organic-inorganic composite hydrogels: compositions, properties, and applications in regenerative medicine.

Hydrogels, formed from crosslinked hydrophilic macromolecules, provide a three-dimensional microenvironment that mimics the extracellular matrix. They served as scaffold materials in regenerative medicine with an ever-growing demand. However, hydrogels composed of only organic components may not fully meet the performance and functionalization requirements for various tissue defects. Composite hydrogels, containing inorganic components, have attracted tremendous attention due to their unique compositions and properties. Rigid inorganic particles, rods, fibers, etc., can form organic-inorganic composite hydrogels through physical interaction and chemical bonding with polymer chains, which can not only adjust strength and modulus, but also act as carriers of bioactive components, enhancing the properties and biological functions of the composite hydrogels. Notably, incorporating environmental or stimulus-responsive inorganic particles imparts smartness to hydrogels, hence providing a flexible diagnostic platform for in vitro cell culture and in vivo tissue regeneration. In this review, we discuss and compare a set of materials currently used for developing organic-inorganic composite hydrogels, including the modification strategies for organic and inorganic components and their unique contributions to regenerative medicine. Specific emphasis is placed on the interactions between the organic or inorganic components and the biological functions introduced by the inorganic components. The advantages of these composite hydrogels indicate their potential to offer adaptable and intelligent therapeutic solutions for diverse tissue repair demands within the realm of regenerative medicine.

Stimulus-Responsive Copper Complex Nanoparticles Induce Cuproptosis for Augmented Cancer Immunotherapy.

Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy of cuproptosis remains limited by the poor delivery efficiency of copper ion carriers. Herein, copper complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver copper complex into cancer cells to induce cuproptosis. Cu(I) NP demonstrate stimulus-responsive release of copper complexes, which results in mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), leading to cuproptosis. Notably, Cu(I) NP not only induce cuproptosis, but also elicit robust immune responses to suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis-based cancer therapy.

Platinum Prodrug Nanoparticles with COX-2 Inhibition Amplify Pyroptosis for Enhanced Chemotherapy and Immune Activation of Pancreatic Cancer.

Pyroptosis, an emerging mechanism of programmed cell death, holds great potential to trigger a robust antitumor immune response. Platinum-based chemotherapeutic agents can induce pyroptosis via caspase-3 activation. However, these agents also enhance cyclooxygenase-2 (COX-2) expression in tumor tissues, leading to drug resistance and immune evasion in pancreatic cancer and significantly limiting the effectiveness of chemotherapy-induced pyroptosis. Here, an amphiphilic polymer (denoted as PHDT-Pt-In) containing both indomethacin (In, a COX-2 inhibitor) and platinum(IV) prodrug (Pt(IV)) is developed, which is responsive to glutathione (GSH). This polymer self-assemble into nanoparticles (denoted as Pt-In NP) that can disintegrate in cancer cells due to the GSH responsiveness, releasing In to inhibit the COX-2 expression, hence overcoming the chemoresistance and amplifying cisplatin-induced pyroptosis. In a pancreatic cancer mouse model, Pt-In NP significantly inhibit tumor growth and elicit both innate and adaptive immune responses. Moreover, when combined with anti-programmed death ligand (α-PD-L1) treatment, Pt-In NP demonstrate the ability to completely suppress metastatic tumors, transforming "cold tumors" into "hot tumors". Overall, the sustained release of Pt(IV) and In from Pt-In NP amplifies platinum-drug-induced pyroptosis to elicit long-term immune responses, hence presenting a generalizable strategy for pancreatic cancer.

Engineered Silica Nanoparticles for Nucleic Acid Delivery.

The development of nucleic acid-based drugs holds great promise for therapeutic applications, but their effective delivery into cells is hindered by poor cellular membrane permeability and inherent instability. To overcome these challenges, delivery vehicles are required to protect and deliver nucleic acids efficiently. Silica nanoparticles (SiNPs) have emerged as promising nanovectors and recently bioregulators for gene delivery due to their unique advantages. In this review, a summary of recent advancements in the design of SiNPs for nucleic acid delivery and their applications is provided, mainly according to the specific type of nucleic acids. First, the structural characteristics and working mechanisms of various types of nucleic acids are introduced and classified according to their functions. Subsequently, for each nucleic acid type, the use of SiNPs for enhancing delivery performance and their biomedical applications are summarized. The tailored design of SiNPs for selected type of nucleic acid delivery will be highlighted considering the characteristics of nucleic acids. Lastly, the limitations in current research and personal perspectives on future directions in this field are presented. It is expected this opportune review will provide insights into a burgeoning research area for the development of next-generation SiNP-based nucleic acid delivery systems.

Boosting catalytic activity toward methanol oxidation reaction for platinum via heterostructure engineering.

Direct methanol fuel cell (DMFC) is hampered by the sluggish methanol oxidation reaction. In this work, we have invited rhodium phosphides (Rh2P) to platinum (Pt) as robust MOR electrocatalyst ascribing the excellent water dissociation capability of Rh2P to generate Pt(OH)ads species to mitigate the CO poisoning. MOR mass activity of Rh2P-Pt/C is enhanced by 2- and 3.5-time with relative to commercial Pt/C and PtRu/C, respectively; additionally, the CO anti-poisoning ability is also boosted by 2.4 folds than Pt/C. The in-situ electrochemical impedance spectroscopy test reveals that the water dissociation is accelerated by Rh2P; moreover, the mutual electronic interplay between Pt and Rh2P contributes to a superior resistance towards electrochemical dissolution and coalescence. The theoretical investigation also indicates that d band center of Pt in Rh2P-Pt is downshifted resulting in a lower CO binding strength.

Enhancing near-infrared II photodynamic therapy with nitric oxide for eradicating multidrug-resistant biofilms in deep tissues.

Nitric oxide (NO) enhanced photodynamic therapy (PDT) is a promising approach to overcome drug tolerance and resistance to biofilm but is limited by its short excitation wavelengths and low yield of reactive oxygen species (ROS). Herein, we develop a compelling degradable polymer-based near-infrared II (NIR-II, 1000-1700 nm) photosensitizer (PNIR-II), which can maintain 50 % PDT efficacy even under a 2.6 cm tissue barrier. Remarkably, PNIR-II is synthesized by alternately connecting the electron donor thiophene to the electron acceptors diketopyrrolopyrrole (DPP) and boron dipyrromethene (BODIPY), where the intramolecular charge transfer properties can be tuned to increase the intersystem crossover rate and decrease the internal conversion rate, thereby stabilizing the NIR-II photodynamic rather than photothermal effect. For exerting a combination therapy to eradicate multidrug-resistant biofilms, PNIR-II is further assembled into nanoparticles (NPs) with a synthetic glutathione-triggered NO donor polymer. Under 1064 nm laser radiation, NPs precisely release ROS and NO that triggered by over-expressed GSH in the biofilm microenvironment, thereby forming more bactericidal reactive nitrogen species (RNS) in vitro and in vivo in the mice model that orderly destroy biofilm of multidrug-resistant Staphylococcus aureus cultures from clinical patients. It thus provides a new outlook for destroy the biofilm of deep tissues.

Spatiotemporal Modulated Scaffold for Endogenous Bone Regeneration via Harnessing Sequentially Released Guiding Signals.

The design of a scaffold that can regulate the sequential differentiation of bone marrow mesenchymal stromal cells (BMSCs) according to the endochondral ossification (ECO) mechanism is highly desirable for effective bone regeneration. In this study, we successfully fabricated a dual-networked composite hydrogel composed of gelatin and hyaluronic acid (termed GCDH-M), which can sequentially release chondroitin sulfate (CS) and magnesium/silicon (Mg/Si) ions to provide spatiotemporal guidance for chondrogenesis, angiogenesis, and osteogenesis. The fast release of CS is from the GCDH hydrogel, and the sustained releases of Mg/Si ions are from poly(lactide-co-glycolide) microspheres embedded in the hydrogel. There is a difference in the release rates between CS and ions, resulting in the ability for the fast release of CS and sustained release of ions. The dual networks between the modified gelatin and hyaluronic acid via covalent bonding and host-guest interactions render the hydrogel with some dynamic feature to meet the differentiation development of BMSCs laden inside the hydrogel, i.e., transforming into a chondrogenic phenotype, further to a hypertrophic phenotype and eventually to an osteogenic phenotype. As evidenced by the results of in vitro and in vivo evaluations, this GCDH-M composite hydrogel was proved to be able to create an optimal microenvironment for embedded BMSCs responding to the sequential guiding signals, which aligns with the rhythm of the ECO process and ultimately boosts bone regeneration. The promising outcome achieved with this innovative hydrogel system sheds light on novel scaffold design targeting bone tissue engineering.

Photoacoustic speckle pattern interferometry for detecting cracks of different sizes.

A system and method for non-destructive detection of cracks of different width and depths based on digital speckle interferometry coupled with pulsed laser excitation is introduced and tested. Based on photoacoustic effect, acoustic waves are induced onto the rear of the samples by pumping a pulsed laser beam on it. The generated mechanical wave propagates from the rear surface of the sample to the front while front surface is monitored by speckle interferometry. In order to acquire information about surface deformation, the front surface is illuminated by continuous wave laser and interference are imaged onto the camera as speckle images. After processing the produced fringe patterns, it indicates the presence and location of the cracks in qualitative way. In this study, the system and method mentioned above are validated by detecting medium density fiberboard with simulated cracks. The fringe patterns from areas with or without defects are compared and discussed. Besides, the system and method to distinguish and predict cracks sizes is proposed and validated.

Fabrication of High Surface Area Fe/Fe3 O4 with Enhanced Performance for Electrocatalytic Nitrogen Reduction Reaction.

The development of high-efficient and large-scale non-precious electrocatalysts to improve sluggish reaction kinetics plays a key role in enhancing electrocatalytic nitrogen reduction reaction (NRR) for ammonia production under mild condition. Herein, Fe3 O4 and Fe supported by porous carbon (denoted as Fe/Fe3 O4 /PC-800) composite with a high specific surface area of 1004.1 m2 g-1 was prepared via a simple template method. On one hand, the high surface area of Fe/Fe3 O4 /PC-800 provides a large area to enhance N2 adsorption and promote more protons and electrons to accelerate the reaction, thereby greatly improving the dynamics. On the other hand, mesoporous Fe/Fe3 O4 /PC-800 provides high electrochemically active surface area for promoting the occurrence of catalytic kinetics. As a result, Fe/Fe3 O4 /PC-800 exhibited significantly enhanced NRR performance with an ammonia yield of 31.15 µg h-1 mg-1 cat. and faraday efficiency of 22.26 % at -0.1 V vs. reversible hydrogen electrode (RHE). This study is expected to provide a new strategy for the synthesis of catalysts with large specific area and pave the way for the foundational research in NRR.

Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway.

Tumor metastases are considered the leading cause of cancer-associated deaths. While clinically applied drugs have demonstrated to efficiently remove the primary tumor, metastases remain poorly accessible. To overcome this limitation, herein, the development of a theranostic nanomaterial by incorporating a chromophore for imaging and a photosensitizer for treatment of metastatic tumor sites is presented. The mechanism of action reveals that the nanoparticles are able to intervene by local generation of cellular damage through photodynamic therapy as well as by systemic induction of an immune response by immunotherapy upon inhibition of the mTOR signaling pathway which is of crucial importance for tumor onset, progression and metastatic spreading. The nanomaterial is able to strongly reduce the volume of the primary tumor as well as eradicates tumor metastases in a metastatic breast cancer and a multi-drug resistant patient-derived hepatocellular carcinoma models in female mice.