Abstract The large-scale consumption and low recycling rate of plastics necessitate effective chemical recycling solutions. High-density polyethylene (HDPE) serves as an ideal carbon source for synthesizing high-value carbon materials such as carbon nanotubes. In this study, a powdered Fe/MgO catalyst was prepared to convert the HDPE into high-quality SWCNTs in a two-stage reactor. Concurrently, reactive force field molecular dynamics simulations elucidated the adsorption, cracking, and carbon diffusion behaviors of pyrolytic intermediates on the Fe surface, along with the kinetics of iron carbide formation. The results demonstrate that Fe/MgO efficiently converts HDPE into SWCNTs, achieving a maximum yield of 33.7% with 1 g of the catalyst containing 2 wt % Fe at 900 °C. The catalyst preferentially adsorbs olefins such as ethylene, suppresses the polymerization and cyclization of small molecules, and thereby promotes SWCNT growth. The high efficiency of the Fe/MgO catalyst is attributed to a unique high-temperature inversion of its spinel structure, which triggers Fe3+ migration from the bulk to the surface. This work not only presents a high-value route for plastic waste utilization but also provides atomic insights into SWCNT synthesis from HDPE using Fe/MgO.
Acute ischemic stroke (AIS) is associated with a high mortality rate and poor prognosis, with a lack of effective therapeutic drugs for post-thrombolytic treatment. MicroRNA-based gene therapy is a promising approach for treating AIS, but its clinical application has been limited due to challenges, such as poor targeting efficiency, unsatisfactory stability, and inadequate cellular uptake. In this study, we successfully developed a microRNA-targeted delivery system based on the tetrahedral framework nucleic acid (tFNA). This nanodelivery system, guided by stroke-homing peptides, effectively targeted and delivered miRNA124 to the ischemic hemisphere. With the assistance of tFNA, miRNA124 efficiently entered cells and exerted therapeutic effects. Additionally, it promoted the transformation of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, reducing neuronal apoptosis and, ultimately, decreasing the infarct size and mortality rate. These findings present a promising therapeutic strategy for the targeted treatment of AIS.
Bone malignant tumors are diseases that endanger human lives and compromise patients' quality of life. Tumors are conventionally treated via chemotherapy; however, nonspecific damage to healthy cells and inefficient targeting of tumor sites often occur, necessitating the development of an innovative treatment paradigm. In this study, a long-circulating thermosensitive liposome encapsulating DOX-loaded BPQDs was constructed to release drugs via pH/NIR response for photothermal-chemotherapy synergistic treatment of osteosarcoma. Initially, BPQDs were synthesized through liquid-phase exfoliation coupled with a solvothermal reaction. Subsequently, DOX was immobilized onto the BPQD surface via electrostatic interactions to ensure efficient chemotherapeutic drug loading. Ultimately, the high-performance Lip-BPQDs-DOX drug delivery system was fabricated by encapsulating BPQDs-DOX within long-circulating thermosensitive liposomes using a thin-film dispersion-extrusion method. The drug delivery system demonstrates a transition in size from large to small, superior photothermal conversion efficiency, pH/NIR-responsive drug release, favorable ex vivo and in vivo biocompatibility, and liposome-mediated, photothermal-chemotherapeutic synergistic anti-tumor effects. These characteristics offer valuable insights for designing multifunctional nanotherapeutic systems for related tumors like osteosarcoma.
In order to enhance the separation efficiency of fine-grained Bayan Obo Niobium Ore, a novel gravity separation equipment named Slime Vibrating Table (SVT) was developed. The SVT employs an electromagnetic drive to generate a reciprocating motion for the table, with a lower stroke and higher frequency than a conventional Slime Shaking Table (SST). Key parameters of SVT, including table slope, wash-water flow rate, vibration voltage, and vibration frequency, were tested for a niobium ore assaying 0.19% Nb2O5 with a particle size below 74 um by 68.78%. Under the optimized condition, SVT was able to obtain a primary concentrate assaying 1.31% Nb2O5 with a recovery of 52.64%, which was 0.22% and 26.59% higher than that of SST, respectively. Size-by-size analysis indicated that the enhanced separation performance of SVT was mainly attributed to its superior recovery of Nb2O5 in the −38 μm fraction. The SVT introduced in this study shows great potential for efficient recovery of fine-grained strategic metals, including rare earths, tantalum, tungsten, tin, and antimony, etc.
Gout is a disease caused by the deposition of sodium urate (MSU) crystals in the joints and tissues. Colchicine (COL) has become the first-line drug for the treatment of acute gout due to its low price and efficacy. However, colchicine is highly cytotoxic and oral administration is prone to cause severe adverse effects on the gastrointestinal tract, liver and kidney. Therefore, this study aimed to develop a novel dermal delivery formulation for addressing the safety concerns of this drug. The researchers used ethosomes encapsulation technology to improve the skin permeability of COL. In addition, in order to improve the performance of the ethosomes, it was screened and determined that the addition of 1.0-1.5 mg of ceramide III (Cer3) per mL of ethosomes as a modifier could significantly enhance the stability of the ethosomes, Cer3/COL-ethosomes (CCE) were successfully constructed. The CCE was then mixed with a cataplasm matrix to produce a colchicine-carrying CCE cataplasm, which demonstrated the superimposed effect of the advantages of the two dosage forms, the ethosomes and the cataplasm. Compared with the traditional delivery method of COL, this topical formulation is an attractive alternative for the treatment of gout as it can achieve effective blood levels without causing fluctuations in blood levels, and has good efficacy and higher safety profile.
beta-amyloid protein (A(3) deposition and plaque formation are key pathological markers leading to Alzheimer's disease (AD), and effective detection of A beta can help in the diagnosis and treatment of AD. Near-infrared fluorescence (NIRF) imaging has emerged as an advanced technique for A beta detection due to its low cost and convenience. In this study, BPQD@PDA-F nanocomposite consisting of black phosphorus quantum dots (BPQD), polydopamine (PDA) and fluorescent probe F were designed for fluorescence detection and modulation of A beta 42 aggregates. BPQD@PDA-F nanocomposite had a good fluorescence response (emission wavelength > 650 nm, and the fluorescence intensity was significantly increased when combined with A beta 42 aggregates), selectivity, fluorescence stability, and could be used for specific fluorescence imaging of A beta plaques in AD mouse brain slices. Meanwhile, BPQD@PDA-F nanocomposite was a multifunctional nanoplatform that could inhibit A beta 42 aggregates and significantly disaggregate A beta 42 aggregates under near-infrared (NIR) irradiation, reduce the toxicity of A beta 42 aggregates to SH-SY5Y cells. In particular, it could better penetrate the blood-brain barrier (BBB) under NIR irradiation. Therefore, BPQD@PDA-F nanocomposite provided an effective strategy for the detection and modulation of A beta 42 aggregates, which was expected to be used for the diagnosis and treatment of AD.
To address the poor solubility and low bioavailability of BCS Class II drugs, exemplified by Bazedoxifene (BZA), in aqueous environments, we utilized gamma-cyclodextrin (gamma-CD), gamma-cyclodextrin metal-organic frameworks (3D-CD-MOFs), and gamma-cyclodextrin metal-organic framework nanosheets (2D-CD-MOFs) as carriers for BZA, and investigated their effects on the drug's solubility and bioavailability. The synthesis and drug-loading processes were optimized, and the impact on the morphology and properties of the CD-MOFs was explored. Molecular docking simulations were conducted to examine the distribution and binding sites of BZA within the CD-MOFs. Finally, the drug loading capacity, solubility, in vitro release, and pharmacokinetics were assessed. The experimental results indicated that the 2D-CD-MOF possessed a high BZA loading capacity and significantly improved drug solubility and bioavailability. The bioavailability of BZA@2D-CD-MOF was 4.47, 1.38 and 4.41 times higher than that of BZA, BZA@3D-CD-MOF and BZA@gamma-CD groups, respectively. This study demonstrates that 2D-CD-MOF nanosheets significantly outperform 3D-CD-MOFs and gamma-CD in enhancing BZA solubility and bioavailability, exhibiting favorable safety profiles. Employing gamma-cyclodextrin metal-organic framework nanosheets for BZA loading presents considerable feasibility and potential for enhancing its solubility and bioavailability.
Ischemic stroke is the leading cause of death in China, accounting for approximately one-third of all stroke-associated deaths worldwide. Currently, thrombolysis is employed for ischemic strokes. However, due to the limited therapeutic window of thrombolytic agents, most patients do not receive the drug at the right time. Moreover, these agents are associated with risks of hemorrhage and reperfusion damage. Herein, Angiopep-2 (ANG)-black phosphorus (BP)-resveratrol (RES), a drug-loaded system, was used to deliver drugs across the blood–brain barrier (BBB). ANG-BP-RES has a uniform size, stable structure, good photothermal effect, and strong drug release ability under near-infrared (NIR) irradiation and acidic conditions. Furthermore, ANG-BP-RES can efficiently target the brain and improve BBB permeability, exerting a significant therapeutic effect against ischemic brain injury, especially after NIR irradiation. ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues. This study offers novel insights into the therapeutic management of ischemic brain injury.
Uncontrolled bleeding, bacterial infections, and slow healing are challenges in wound treatment. Hence, there is an urgent need to develop multifunctional wound dressing materials that can meet the needs of all stages of wound healing and minimize human injury. This study focuses on the combination of two-dimensional nanomaterials with novel composite sponge wound dressings through the in situ modification technique. Inorganic metal particles were modified on the surface of negatively charged MXene nanosheets, and the resulting MXeneAgNPs nanocomposites were crosslinked to form a dopamine-bacterial cellulose (BC) filamentous gel network, and bacterial cellulose-PDA-MXene-AgNPs composite sponges (BCP-MAg composite sponges) were prepared through low-temperature freeze-drying. During the hemostatic phase, the high density of BCP-MAg composite sponges with high porosity, specific surface area, and excellent fluid-absorbing ability achieved rapid hemostasis. In the subsequent inflammatory phase, BCP-MAg composite sponge combined with photothermal therapy (PTT) down-regulates pro-inflammatory factors (TNF-alpha, IL-6) to reduce inflammation and facilitate the transition to the proliferative phase. During the proliferative phase, BCP-MAg composite sponges promote collagen deposition and re-epithelialization as well as angiogenesis, providing comprehensive support for wound repair and regeneration and accelerating the healing process. During the remodeling phase, the good biocompatibility of BCP-MAg composite sponge helps the wound to heal more naturally during the remodeling phase. Overall, the composite sponge has good biocompatibility, excellent rapid hemostatic properties, strong antimicrobial efficacy, and effective promotion of wound healing.
In diabetic wounds, the presence of hyperglycemia is often accompanied by a persistent inflammatory response, oxidative stress damage, impaired angiogenesis and bacterial infections around the wound, resulting in impaired proliferation of dermal and epidermal cells and impaired skin regeneration in diabetic wounds. To solve the above problems, this study designed a near-infrared (NIR) light-responsive multifunctional poloxamer hydrogel (EGF/PDA-MXene Gel). The Gel is composed of two-dimensional nanomaterials (2D NMs) MXene as the core, modified by polymer, further loaded with epidermal growth factor (EGF), and has antibacterial, antioxidant, photothermal properties. Meanwhile, EGF/PDA-MXene Gel can be used as a drug repository, alleviating the problem of short half-life, and realizing the sustained release of EGF. The NIR photothermal property induces protein denaturation leading to the death of pathogenic bacteria, avoiding the common clinical problem of antibiotic resistance. In addition, EGF/PDA-MXene Gel promotes diabetic chronic wound healing by promoting epidermal regeneration, collagen deposition, angiogenesis, and several other mechanisms. Therefore, the Gel preparation strategies that combine bioactive molecules with 2D NMs, which maintains the activity of EGF while exploiting the antimicrobial advantages of 2D NMs photothermally, provide a new and promising therapeutic approach for accelerating the repair of chronic infected wounds.
Background Injectable bone cement is commonly used in clinical orthopaedics to fill bone defects, treat vertebral compression fractures, and fix joint prostheses during joint replacement surgery. Poly(propylene fumarate) (PPF) has been proposed as a biodegradable and injectable alternative to polymethylmethacrylate (PMMA) bone cement. Recently, there has been considerable interest in two-dimensional (2D) black phosphorus nanomaterials (BPNSs) in the biomedical field due to their excellent photothermal and osteogenic properties. In this study, we investigated the biological and physicochemical qualities of BPNSs mixed with PPF bone cement created through thermal cross-linking. Methods PPF was prepared through a two-step process, and BPNSs were prepared via a liquid phase stripping method. BP/PPF was subsequently prepared through thermal cross-linking, and its characteristics were thoroughly analysed. The mechanical properties, cytocompatibility, osteogenic performance, degradation performance, photothermal performance, and in vivo toxicity of BP/PPF were evaluated. Results BP/PPF exhibited low cytotoxicity levels and mechanical properties similar to that of bone, whereas the inclusion of BPNSs promoted preosteoblast adherence, proliferation, and differentiation on the surface of the bone cement. Furthermore, 200 BP/PPF demonstrated superior cytocompatibility and osteogenic effects, leading to the degradation of PPF bone cement and enabling it to possess photothermal properties. When exposed to an 808-nm laser, the temperature of the bone cement increased to 45–55 °C. Furthermore, haematoxylin and eosin-stained sections from the in vivo toxicity test did not display any anomalous tissue changes. Conclusion BP/PPF exhibited mechanical properties similar to that of bone: outstanding photothermal properties, cytocompatibility, and osteoinductivity. BP/PPF serves as an effective degradable bone cement and holds great potential in the field of bone regeneration.
The cell membrane serves as a barrier against the free entry of foreign substances into the cell. Limited by factors such as solubility and targeting, it is difficult for some drugs to pass through the cell membrane barrier and exert the expected therapeutic effect. Two-dimensional nanomaterial (2D NM) has the advantages of high drug loading capacity, flexible modification, and multimodal combination therapy, making them a novel drug delivery vehicle for drug membrane attachment and intracellular transport. By modulating the surface properties of nanocarriers, it is capable of carrying drugs to break through the cell membrane barrier and achieve precise treatment. In this review, we review the classification of various common 2D NMs, the primary parameters affecting their adhesion to cell membranes, and the uptake mechanisms of intracellular transport. Furthermore, we discuss the therapeutic potential of 2D NMs for several major disorders. We anticipate this review will deepen researchers' understanding of the interaction of 2D NM drug carriers with cell membrane barriers, and provide insights for the subsequent development of novel intelligent nanomaterials capable of intracellular transport.
Glycyrrhiza inflata Bat. produces a lot of licorice waste after water extraction, which also retains abundant total flavonoids (TFs) and licochalcone A. However, licorice residue is often wasted due to the lack of good utilization of resources in practical applications. This study first screened the optimal membrane pore size and resin type and then explored the mechanism and conditions of the adsorption of TFs on the resin. Then, different combinations and sequences of membrane and macroporous resin (MR) methods were investigated. It was found that using the membrane method for initial purification, followed by the MR method for further purification, yielded the best purification results. Next, response surface methodology was utilized to investigate the resin’s dynamic desorption conditions for TFs. Finally, the TF purity increased from 32.9% to 78.2% (2.38-fold) after purification by a combined membrane–MR process; the purity of licochalcone A increased from 11.63 mg·g−1 to 22.70 mg·g−1 (1.95-fold). This study verified the feasibility of enriching TFs and licochalcone A from licorice residue using a membrane–MR coupling method. In addition, a quality-control method was established using a fingerprinting method on the basis of ultrahigh-performance liquid chromatography (UPLC) to ensure the stability of the enrichment process.
The management of osteosarcoma presents a significant challenge, and the creation of an intelligent synergistic drug delivery system is broadly acknowledged as a promising approach to therapy. Hence, in this study, a temperature-sensitive hydrogel containing DOX-loaded and folic acid-modified BPNSs that can be injected was developed to enable drug release via a pH/NIR response, aimed at synergistic photothermal-chemotherapeutic treatment of osteosarcoma. The active targeting of BPNSs-PEG-FA/DOX involved liquid-phase stripping and electrostatic adsorption, leading to the preparation of the BPNSs-PEG-FA/DOX aqueous dispersion hybrid hydrogel matrix as a BPNSs-PEG-FA/DOX@Hydrogel through a cold method. This composite hydrogel exhibits favorable through-needle properties, superior photothermal conversion efficiency, pH/NIR intelligent responsiveness, and controlled delayed-release drug release capabilities, along with favorable in vitro cellular biocompatibility. It also demonstrates effective in vitro and in vivo active targeting, controlled delayed release, and synergistic photothermal-chemotherapeutic anti-osteosarcoma activity, showing considerable promise for the treatment of superficial tumors such as osteosarcoma.
Abstract Alhagi honey (AH) is produced in arid and hot areas of Central Asia, and its polysaccharides (AP) are widely known for their activity in the treatment of intestinal diseases such as diarrhea. However, the therapeutic potential and mechanism of AP in ulcerative colitis (UC) remain unclear. Here, AH polysaccharide‐2 (AP2), a polysaccharide with the highest content in AP, was isolated and evaluated for its effects on dextran sulfate sodium (DSS)‐induced UC in mice. AP2 was found to alleviate UC symptoms and regulate gut microbiota dysbiosis by decreasing Helicobacter levels and increasing Lactobacillus levels. Analysis of PICRUSt2 predicted that AP2 may regulate carbohydrate and amino acid metabolism, and metabolomic analysis confirmed that AP2 promotes the metabolism of tryptophan to produce kynurenic acid (kyna). Moreover, kyna acted as an aryl hydrocarbon receptor (AhR) ligand, which activated AhR to increase the expression of the tight junction proteins claudin‐1 and occludin. Interestingly, AP2 showed similar effects in protecting the intestinal barrier and alleviating colitis as the AhR agonist 6‐formylindolo[3,2‐b]carbazole, and the AhR antagonist CH223191 partially blocked the therapeutic effect of AP2 in UC mice, indicating that the anti‐UC effect of AP2 was AhR dependent. These findings demonstrate that AP2 alleviates UC by regulating the gut microbiota and promoting tryptophan metabolism to generate kyna‐activated AhR. The insights gained from this study could help in the future development of AP2 as a drug candidate or functional food for the treatment of UC.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammation, joint pain, and cartilage degradation. The fluctuating nature of RA often necessitates long-term oral administration of treatment drugs, which can unfortunately lead to adverse effects such as gastrointestinal discomfort and hepatic and renal dysfunction. Therefore, a percutaneous local delivery method for the release of inflammatory modulators in arthritic joints represents a promising therapeutic approach for RA. In this study, we have developed a unique and innovative therapeutic platform (named BP-Rut@Gel). This hydrogel was formulated by incorporating the drug Rutin (Rut) into Black phosphorus nanosheets (BP) and subsequently integrating them within a Hyaluronic Acid (HA) and Polyvinyl Alcohol (PVA) matrix to create a composite hydrogel. Notably, Secondly, photothermal therapy (PTT) under Near-Infrared Irradiation (NIR) and anti-inflammatory drugs synergistically worked together to efficiently quell inflammation and enhance therapeutic effectiveness. Additionally, toxicity experiments have revealed that our synthesized black phosphorus nanosheet composite hydrogel possesses excellent biocompatibility and significantly reduces the inflammatory response in RA joints. Given these remarkable properties, our BP-Rut@Gel hydrogel held significant promise and demonstrated immense clinical potential for the treatment of RA.
The use of facile methods to synthesize environmentally friendly and multifunctional hydrogel dressings is still a major challenge in development. Herein, Turkish gall extract (TGE) and carboxymethyl chitosan (CMCS) were combined and sprayed using a dual syringe to form a multifunctional TGE-CMCS hydrogel (TC gel) in one step through abundant hydrogen bonding between functional groups as a green approach. TC gel showed rapid gelation at 19.0 ± 2.9 s. Apart from the advantage of being able to adapt to different wound shapes, TC gel retained the antioxidant, antibacterial, hemostatic and anti-inflammatory properties of TGE. In vitro antibacterial experiments showed that TC-gel eliminated 98.27 ± 0.79 % of Staphylococcus aureus and 98.87 ± 1.08 % of Escherichia coli. Compared with TGE or CMCS alone, TC gel accelerates skin wound healing due to its three-dimensional network structure and continuous release of active components at the wound site, enhancing re-epithelialization, improving collagen deposition, and increasing angiogenesis. The wound healing rate of full-thickness skin defect rats treated with TC gel was 93.98 ± 0.63 % on the 10th day. These results suggest that TC gel combined with a facile and scalable manufacturing method is a promising multifunctional wound dressing for clinical wound management.
The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 μM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 μM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.
To date, plant medicine research has focused mainly on the chemical compositions of plant extracts and their medicinal effects. However, the therapeutic or toxic effects of nanoparticles in plant extracts remain unclear. In this study, large numbers of spherical nanoparticles were discovered in some plant extracts. Nanoparticles in Turkish galls extracts were used as an example to examine their pH responsiveness, free radical scavenging, and antibacterial capabilities. By utilizing the underlying formation mechanism of these nanoparticles, a general platform to produce spherical nanoparticles via direct self-assembly of Turkish gall extracts and various functional proteins was developed. The results showed that the nanoparticles retained both the antibacterial ability and intracellular carrier ability of the original protein or catechol. This work introduces a new member of the plant-derived edible nanoparticle (PDEN) family, establishes a simple and versatile platform for mass production nanoparticles, and provides new insight into the formation mechanism of nanoparticles during plant extraction.