NAD+ precursors promote the restoration of spermatogenesis in busulfan-treated mice through inhibiting Sirt2-regulated ferroptosis.

Rationale: In recent years, nicotinamide adenine dinucleotide (NAD+) precursors (Npre) have been widely employed to ameliorate female reproductive problems in both humans and animal models. However, whether and how Npre plays a role in the male reproductive disorder has not been fully clarified. Methods: In the present study, a busulfan-induced non-obstructive azoospermic mouse model was used, and Npre was administered for five weeks following the drug injection, with the objective of reinstating spermatogenesis and fertility. Initially, we assessed the NAD+ level, germ cell types, semen parameters and sperm fertilization capability. Subsequently, testis tissues were examined through RNA sequencing analysis, ELISA, H&E, immunofluorescence, quantitative real-time PCR, and Western blotting techniques. Results: The results indicated that Npre restored normal level of NAD+ in blood and significantly alleviated the deleterious effects of busulfan (BU) on spermatogenesis, thereby partially reestablishing fertilization capacity. Transcriptome analysis, along with recovery of testicular Fe2+, GSH, NADPH, and MDA levels, impaired by BU, and the fact that Fer-1, an inhibitor of ferroptosis, restored spermatogenesis and semen parameters close to CTRL values, supported such possibility. Interestingly, the reduction in SIRT2 protein level by the specific inhibitor AGK2 attenuated the beneficial effects of Npre on spermatogenesis and ferroptosis by affecting PGC-1α and ACLY protein levels, thus suggesting how these compounds might confer spermatogenesis protection. Conclusion: Collectively, these findings indicate that NAD+ protects spermatogenesis against ferroptosis, probably through SIRT2 dependent mechanisms. This underscores the considerable potential of Npre supplementation as a feasible strategy for preserving or restoring spermatogenesis in specific conditions of male infertility and as adjuvant therapy to preserve male fertility in cancer patients receiving sterilizing treatments.

Natural Nano-Minerals (NNMs): Conception, Classification and Their Biomedical Composites.

Natural nano-minerals (NNMs) are minerals that are derived from nature with a size of less than 100 nm in at least one dimension in size. NNMs have a number of excellent properties due to their unique nanostructure and have been applied in various fields in recent years. They are rising stars in various disciplines, such as materials, biomedicine, and chemistry, taking advantage of their huge surface area, multiple active sites, excellent adsorption capacity, large quantity, low cost, and nontoxicity, etc. To provide a more comprehensive overview of NNMs and the biomedical applications of NNMs-based nanocomposites, this review classifies NNMs into three types by dimension, lists the structure and properties of typical NNMs, and illustrates their biomedical applications. Furthermore, a novel concept of natural nanomineral medical materials (NNMMs) is proposed, focusing on the medical value of NNMs. In addition, this review attempts to address the current challenges and delineate future directions for the advancement of NNMs. With the deepening of biomedical applications, it is believed that NNMMMs will inevitably play an important role in the field of human health and contribute to its promotion.

The mechanism of intrinsic peroxidase (POD)-like activity of attapulgite.

Natural attapulgite (ATP) is a promising substitute for existing artificial nanozymes due to its intrinsic enzymatic activity. However, the active center of ATP's inherent enzymatic activity has not yet been revealed, which limits its further design and activity optimization. Studying the active center of mineral materials can be extremely challenging due to their complexity. Here, we demonstrated that Fe is the primary element in ATP responsible for peroxidase (POD)-like activity through theoretical speculation and experimental verification. More importantly, we found that the ratio of Fe2+/Fe3+ is responsible for the district POD-like activity of ATP from different regions with the same Fe content. Additionally, three facile strategies, including grinding, heat treatment, and acid treatment, were demonstrated to increase the relative Fe content and thus optimize the POD-like activity of ATP. Finally, ATP was used to detect the concentration of H2O2, enabling the detection of low concentrations (0.11-1.76 mM) of H2O2. This study serves as a novel reference for the future design and performance optimization of nanozymes that are based on ATP and clay minerals.

The hemostatic performance and mechanism of palygorskite with structural regulate by oxalic acid gradient leaching.

Palygorskite (Pal) is a naturally available one-dimensional clay mineral, featuring rod-shaped morphology, nanoporous structure, permanent negative charges as well as abundant surface hydroxyl groups, exhibiting promising potential as a natural hemostatic material. In this study, the hemostatic performance and mechanisms of Pal were systematically investigated based on the structural regulate induced by oxalic acid (OA) gradient leaching from perspectives of structure, surface attributes and ion release.In vitroandin vivohemostasis evaluation showed that Pal with OA leaching for 1 h exhibited a superior blood procoagulant effect compared with the raw Pal as well as the others leached for prolonging time. This phenomenon might be ascribed to the synergistic effect of the intact nanorod-like morphology, the increase in the surface negative charge, the release of metal ions (Fe3+and Mg2+), and the improved blood affinity, which promoted the intrinsic coagulation pathway, the fibrinogenesis and the adhesion of blood cells, thereby accelerating the formation of robust blood clots. This work is expected to provide experimental and theoretical basis for the construction of hemostatic biomaterials based on clay minerals.

PGC-1α-Coordinated Hypothalamic Antioxidant Defense Is Linked to SP1-LanCL1 Axis during High-Fat-Diet-Induced Obesity in Male Mice.

High-fat-diet (HFD)-induced obesity parallels hypothalamic inflammation and oxidative stress, but the correlations between them are not well-defined. Here, with mouse models targeting the antioxidant gene LanCL1 in the hypothalamus, we demonstrate that impaired hypothalamic antioxidant defense aggravates HFD-induced hypothalamic inflammation and obesity progress, and these could be improved in mice with elevated hypothalamic antioxidant defense. We also show that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a critical transcriptional coactivator, is implicated in regulating hypothalamic LanCL1 transcription, in collaboration with SP1 through a direct interaction, in response to HFD-induced palmitic acid (PA) accumulation. According to our results, when exposed to HFD, mice undergo a process of overwhelming hypothalamic antioxidant defense; short-time HFD exposure induces ROS production to activate PGC-1α and elevate LanCL1-mediated antioxidant defense, while long-time exposure promotes ubiquitin-mediated PGC-1α degradation and suppresses LanCL1 expression. Our findings show the critical importance of the hypothalamic PGC-1α-SP1-LanCL1 axis in regulating HFD-induced obesity, and provide new insights describing the correlations of hypothalamic inflammation and oxidative stress during this process.

Modulation of Deep-Red to Near-Infrared Room-Temperature Charge-Transfer Phosphorescence of Crystalline "Pyrene Box" Cages by Coupled Ion/Guest Structural Self-Assembly.

Organic cocrystals obtained from multicomponent self-assembly have garnered considerable attention due to their distinct phosphorescence properties and broad applications. Yet, there have been limited reports on cocrystal systems that showcase efficient deep-red to near-infrared (NIR) charge-transfer (CT) phosphorescence. Furthermore, effective strategies to modulate the emission pathways of both fluorescence and phosphorescence remain underexplored. In this work, we dedicated our work to four distinct self-assembled cocrystals called "pyrene box" cages using 1,3,6,8-pyrenetetrasulfonate anions (PTS4-), 4-iodoaniline (1), guanidinium (G+), diaminoguanidinium (A2G+), and hydrated K+ countercations. The binding of such cations to PTS4- platforms adaptively modulates their supramolecular stacking self-assembly with guest molecules 1, allowing to steer the fluorescence and phosphorescence pathways. Notably, the confinement of guest molecule 1 within "pyrene box" PTSK{1} and PTSG{1} cages leads to an efficient deep-red to NIR CT phosphorescence emission. The addition of fuming gases like triethylamine and HCl allows reversible pH modulations of guest binding, which in turn induce a reversible transition of the "pyrene box" cage between fluorescence and phosphorescence states. This capability was further illustrated through a proof-of-concept demonstration in shrimp freshness detection. Our findings not only lay a foundation for future supramolecular designs leveraging weak intermolecular host-guest interactions to engineer excited states in interacting chromophores but also broaden the prospective applications of room-temperature phosphorescence materials in food safety detection.

Bioinspired polymeric supramolecular columns as efficient yet controllable artificial light-harvesting platform.

Light-harvesting is an indispensable process in photosynthesis, and researchers have been exploring various structural scaffolds to create artificial light-harvesting systems. However, achieving high donor/acceptor ratios for efficient energy transfer remains a challenge as excitons need to travel longer diffusion lengths within the donor matrix to reach the acceptor. Here, we report a polymeric supramolecular column-based light-harvesting platform inspired by the natural light-harvesting of purple photosynthetic bacteria to address this issue. The supramolecular column is designed as a discotic columnar liquid crystalline polymer and acts as the donor, with the acceptor intercalated within it. The modular columnar design enables an ultrahigh donor/acceptor ratio of 20000:1 and an antenna effect exceeding 100. Moreover, the spatial confinement within the supramolecular columns facilitates control over the energy transfer process, enabling dynamic full-color tunable emission for information encryption applications with spatiotemporal regulation security.

Topological transformation across different dimensions of supramolecular polymer via photo-isomerization.

Herein, we report a novel topological transformable supramolecular polymer capable of converting its architecture from a two-dimensional to a one-dimensional structure. The transformative process is achieved by the precise control of the steric configuration of constituent monomers via photo-isomerization.

Progress and future prospects of hemostatic materials based on nanostructured clay minerals.

The occurrence of uncontrolled hemorrhage is a significant threat to human life and health. Although hemostatic materials have made remarkable advances in the biomaterials field, it remains a challenge to develop safe and effective hemostatic materials for global medical use. Natural clay minerals (CMs) have long been used as traditional inorganic hemostatic agents due to their good hemostatic capability, biocompatibility and easy availability. With the advancement of science, technology and ideology, CM-based hemostatic materials have undergone continuous innovations by integrating new inspirations with conventional concepts. This review systematically summarizes the hemostatic mechanisms of different natural CMs based on their nanostructures. Moreover, it also comprehensively reviews the latest research progress for CM-based hemostatic hybrid and nanocomposite materials, and discusses the challenges and developments in this field.

Mechanochemical preparation of low cost kaolinite-based BiVO4hybrid pigments with high near infrared reflectance.

For accelerate construction of the energy and resource-saving and environmental-friendly society, cleaner preparation of low-cost and high-performance colorful near-infrared reflective inorganic pigments with the decorative function is indispensable to reduce the hazards of urban heat island and simultaneously beautify the appearance of the buildings. Due to the non-toxicity, good chemical stability and narrow band gap, BiVO4has been becoming a promising environment-friendly yellow inorganic pigments among the conventional heavy metals-containing inorganic pigments. In this study, the low-cost and brilliant kaolinite-based BiVO4hybrid pigments were fabricated by cleaner mechanochemical method based on cheap and abundant kaolinite using crystal water of the hydrated metal salts as trace solvent, which could effectively promote the interaction of the involved components at the molecular level during grinding and then decreased the mass transfer resistance for the formation of monoclinic scheelite BiVO4in the following calcination. The obtained hybrid pigments at the optimal preparation conditions exhibited brilliant color properties (D65-10°,L*= 83.45 ± 0.08,a*= 4.17 ± 0.08,b*= 88.59 ± 0.17), high near-infrared reflectance of 86.22%, infrared solar reflectance of 88.14% and high emissivity of 0.9369 in the waveband of 8-13µm. Furthermore, the hybrid pigments could be used for coloring epoxy resin with high emissivity of 0.8782 in 8-13µm. Therefore, the brilliant and low-cost kaolinite-based bismuth yellow hybrid pigments have the enormous potential to be served as colorful functional nanofillers for cooling roofing materials.

Preparation of Hybrid Nanopigments with Excellent Environmental Stability, Antibacterial and Antioxidant Properties Based on Monascus Red and Sepiolite by One-Step Grinding Process.

This study is focused on the preparation, characterization, and multifunctional properties of intelligent hybrid nanopigments. The hybrid nanopigments with excellent environmental stability and antibacterial and antioxidant properties were fabricated based on natural Monascus red, surfactant, and sepiolite via a facile one-step grinding process. The density functional theory calculations demonstrated that the surfactants loaded on sepiolite were in favor of enhancing the electrostatic, coordination, and hydrogen bonding interactions between Monascus red and sepiolite. Thus, the obtained hybrid nanopigments exhibited excellent antibacterial and antioxidant properties, with an inhibition effect on Gram-positive bacteria that was superior to that of Gram-negative bacteria. In addition, the scavenging activity on DPPH and hydroxyl free radicals as well as the reducing power of hybrid nanopigments were higher than those of hybrid nanopigments prepared without the addition of the surfactant. Inspired by nature, gas-sensitive reversible alochroic superamphiphobic coatings with excellent thermal and chemical stability were successfully designed by combining hybrid nanopigments and fluorinated polysiloxane. Therefore, intelligent multifunctional hybrid nanopigments have great application foreground in related fields.

Metal binding pharmacophore click-derived discovery of new broad-spectrum metallo-ß-lactamase inhibitors.

The emergence of metallo-ß-lactamases (MBLs) confers resistance to nearly all the ß-lactam antibiotics, including carbapenems. Currently, there is a lack of clinically useful MBL inhibitors, making it crucial to discover new inhibitor chemotypes that can potently target multiple clinically relevant MBLs. Herein we report a strategy that utilizes a metal binding pharmacophore (MBP) click approach to identify new broad-spectrum MBL inhibitors. Our initial investigation identified several MBPs including phthalic acid, phenylboronic acid and benzyl phosphoric acid, which were subjected to structural transformations using azide-alkyne click reactions. Subsequent structure-activity relationship analyses led to the identification of several potent broad-spectrum MBL inhibitors, including 73 that manifested IC50 values ranging from 0.00012 µM to 0.64 µM against multiple MBLs. Co-crystallographic studies demonstrated the importance of MBPs in engaging with the MBL active site anchor pharmacophore features, and revealed the unusual two-molecule binding modes with IMP-1, highlighting the critical role of flexible active site loops in recognizing structurally diverse substrates/inhibitors. Our work provides new chemotypes for MBL inhibition and establishes a MBP click-derived paradigm for inhibitor discovery targeting MBLs as well as other metalloenzymes.

Supramolecular coassembly: monomer pair design, morphology regulation and functional application.

Supramolecular self-assembly of molecules into highly ordered architectures is attractive for developing various advanced functional materials. Compared to the assemblies of one single building block, supramolecular coassembly (SCA) of multiple component systems has recently emerged as a promising approach for generating highly functional and complex structures. The assembly and integration of multiple building blocks at the molecular level are of paramount importance for constructing SCA systems with sophisticated architectures and diverse functions. This feature article highlights the recent advances and future trends in SCAs, ranging from their synthetic strategies, morphological control, to functional applications. The monomer pairs used to synthesize SCAs are rationalized into two classes including structural monomer pairs and functional monomer pairs. The assembly behaviors are then discussed according to the dimensionality of the coassembled morphologies from zero to three dimensions. Finally, the emergent functions and applications of SCAs are highlighted such as adsorption, catalysis, optoelectronics, and biomedicines.

Incorporation of mixed-dimensional palygorskite clay into chitosan/polyvinylpyrrolidone nanocomposite films for enhancing hemostatic activity.

Clay mineral-based hemostatic materials have attracted much attention in recent years, but it is scarce to report the hemostatic nanocomposite films containing natural mixed-dimensional clay composed of natural one-dimensional and two-dimensional clay minerals. In this study, the high-performance hemostatic nanocomposite films were facilely prepared by incorporating the natural mixed-dimensional palygorskite clay leached by oxalic acid (O-MDPal) into chitosan/polyvinylpyrrolidone (CS/PVP) matrix. By contrast, the obtained nanocomposite films exhibited the higher tensile strength (27.92 MPa), lower water contact angel (75.40°), better degradation, thermal stability and biocompatibility after incorporation of 20 wt% of O-MDPal, suggesting that O-MDPal contributed to enhancing the mechanical performance and water holding capacity of the CS/PVP nanocomposite films. Compared with the medical gauze and CS/PVP matrix groups, the nanocomposite films also indicated excellent hemostatic performance evaluated by blood loss and hemostasis time indexes based on the mouse tail amputation model, which might be ascribed to the enriched hemostatic functional sites, and hydrophilic surface, robust physical barrier role of nanocomposite films. Therefore, the nanocomposite film exhibited a promising practical application in wound healing.

Thermo-Induced Bathochromic Emission in Columnar Discotic Liquid Crystals Realized by Intramolecular Planarization.

Most organic thermochromic fluorescent materials exhibit thermo-induced hypsochromic emission due to the formation of excimers in ordered molecular solids; however, it is still a challenge to endow them with bathochromic emission despite its significance in making up the field of thermochromism. Here, a thermo-induced bathochromic emission in columnar discotic liquid crystals is reported realized by intramolecular planarization of the mesogenic fluorophores. A three-armed discotic molecule of dialkylamino-tricyanotristyrylbenzene was synthesized, which preferred to twist out of the core plane to accommodate ordered molecular stacking in hexagonal columnar mesophases, giving rise to bright green monomer emission. However, intramolecular planarization of the mesogenic fluorophores occurred in isotropic liquid increasing the conjugation length, and as a result led to thermo-induced bathochromic emission from green to yellow light. This work reports a new concept in the thermochromic field and provides a novel strategy to achieve fluorescence tuning from intramolecular actions.

Incorporation of clay minerals into magnesium phosphate bone cement for enhancing mechanical strength and bioactivity.

The poor mechanical strength and bioactivity of magnesium phosphate bone cements (MPCs) are the vital defects for bone reconstruction. Clay minerals have been widely used in biomedical field due to the good reinforcing property and cytocompatibility. Here, laponite, sepiolite or halloysite were incorporated to fabricate MPCs composite, and the composition, microstructure, setting time, compressive strength, thermal stability, degradation performance,in vitrobioactivity and cell viability of MPCs composite were investigated. The results suggested that the MPCs composite possessed appropriate setting time, high mechanical strength and good thermal stability. By contrast, MPCs composite containing 3.0 wt.% of sepiolite presented the highest compressive strength (33.45 ± 2.87 MPa) and the best thermal stability. The degradation ratio of MPCs composite was slightly slower than that of MPCs, and varied in simulated body fluid and phosphate buffer solution. Therefore, the obtained MPCs composite with excellent bioactivity and cell viability was expected to meet the clinical requirements for filling bone defect.

Phyto-Mediated Controllable Synthesis of ZnO Clusters with Bactericidal Activity.

The rapid development of antibiotic resistance has been considered a major threat to public health. Nanomaterials have risen to be an effective weapon to tackle this problem through multiple antibacterial mechanisms. The improved and tailored physiochemical properties of fine-tuned secondary nanoarchitectures contribute to the superior bactericidal actions of metal oxide structures. However, it is still challenging to construct secondary structures through mild green manufacturing methods. Here, we report the preferred antibacterial ZnO nanocrystal clusters formed by a green structure-tuning synthesis process, in which the primary ZnO nanoparticles with sizes <10 nm were assembled into different forms of clusters depending on the zinc salt concentration and temperature. ZnO clusters with a stable loose-assembly structure and a rougher surface exhibited better bactericidal ability with minimal inhibitory concentrations of 0.5 and 0.1 mg/mL against Escherichia coli and Staphylococcus aureus, respectively. The underlying mechanism is related to enhancing contact with bacteria, releasing small ZnO nanoparticles, and generating additional reactive oxygen species, which could aggravate the damage to bacterial cell membrane and eventually lead to bacterial death. Furthermore, attachment of phenolic compounds from olive leaf extract would promote membrane penetration by ZnO nanoparticles, resulting in the improvement of antibacterial activities, which profit from the green route mediated by Olea europaea leaf extract that could structure-tune ZnO nanocrystal clusters in one simple step that retains the active ingredients on the nanoparticles. This work proposes a feasible and clean strategy to improve the structure-bioactivity relationship of ZnO by controlling its growth into a preferable structure, and the developed ZnO clusters have a good prospect in antibacterial applications because of their excellent performance and green fabrication method.

DRR1 promotes neuroblastoma cell differentiation by regulating CREB expression.

BACKGROUND: Neuroblastoma is the most common cancer in infants and the most common extracranial solid tumor in childhood. DRR1 was identified to be downregulated in poorly differentiated ganglion cells from neuroblastoma model mice. However, the roles of DRR1 in neuroblastoma remain largely unclear. METHODS: The neuroblastoma cells were induced to differentiate, and the expression of DRR1 was detected. The expression of the neuroblastoma cell differentiation markers was analyzed in DRR1 shRNA- or DRR1-expressing vector-treated neuroblastoma cells. The downstream genes of DRR1 were screened with ChIP-seq assay. Finally, TNB1 cells were infected with DRR1 shRNA and CREB expressing vector containing lentivirus, and the expression of the cell differentiation markers, cell cycle distribution and tumor growth were analyzed. RESULTS: The expression of DRR1 was increased in differentiated neuroblastoma cells, and downregulation of DRR1 expression inhibited the differentiation of neuroblastoma cells. Further experiments indicated that CREB is a candidate downstream gene of DRR1, and it mediates neuroblastoma cell differentiation. Moreover, overexpression of CREB rescued the effect of DRR1 shRNA on cell differentiation, cell cycle distribution and tumor growth in neuroblastoma. CONCLUSIONS: DRR1-CREB axis modulates the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients. IMPACT: DRR1 is involved in regulation of the differentiation of neuroblastoma. Binding with actin is essential for DRR1 to regulate neuroblastoma cell differentiation. CREB is a candidate downstream gene of DRR1 in regulating of the differentiation of neuroblastoma.

Incorporation of silver nanoparticles/curcumin/clay minerals into chitosan film for enhancing mechanical properties, antioxidant and antibacterial activity.

It is popular that natural organics are served as green reducing and end-capping reagent for synthesis of functional nanoparticles. In this study, curcumin, a natural pigment, was employed to prepare silver nanoparticles (AgNPs) as a coloring, reducing and end-capping agent by an eco-friendly, economic and facile approach in the presence of different clay minerals, including palygorskite, montmorillonite and mixed-dimensional palygorskite clay. It was found that the phenolic hydroxyl groups or carbonyl groups of curcumin played a crucial role to reduce silver ions into AgNPs with the ginger color. Meanwhile, incorporation of clay minerals could induce the in-situ heterogeneous nucleation of AgNPs on the surface or/and interlayer of the involved clay minerals. It effectively prevented from the aggregations and resulted in uniform dispersion of AgNPs with a diameter of 30-40 nm. Furthermore, the as-prepared nanocomposites exhibited a higher antioxidant (>90%) and antibacterial activity. Due to the synergistic effect of each component among the nanocompositions, the nanocomposites derived from different clay minerals were employed as multifunctional nanofillers to design functional chitosan composite films. By contrast, the chitosan composite films containing curcumin-capped AgNPs/mixed-dimensional palygorskite clay nanocomposites exhibited the best mechanical properties, antioxidant and antibacterial activities. Compared with the chitosan films, the tensile strength and elongation at break of composite films increased by 15.90 MPa and 27.27%, respectively. The inactivation rate of the composite films against Escherichia coli and Staphylococcus aureus had reached 100%. Therefore, the obtained composite film with the ginger color exhibited excellent mechanical, water resistance, antioxidant and antibacterial properties, and it was expected to develop a great potential functional packaging materials.

Scale-up disaggregation of palygorskite crystal bundles via ultrasonic process for using as potential drilling fluid.

High-efficient disaggregation of palygorskite (PAL) crystal aggregates into individual nanorods is the key to exploiting its nanometer properties, which remains a challenge at present. The sonochemical cavitation effects have been successfully employed for the intensification of physical and chemical processing applications, but it still lacks the relevant study on the scale-up disaggregation of PAL crystal bundles. Here, the energy-efficient, scale-up ultrasonic process was developed to disaggregate PAL aggregates in batches, and the effects of ultrasonic treatment time, temperature, and power on physicochemical features of PAL were systematically investigated. The results showed that the single dispersed PAL nanorods could be continuously produced by sonicating 15 wt% of PAL suspension at 20 kHz, 2000 W and 30 °C for 5 min retaining the original nanorod length and layered-chain structure. It also greatly improved the dispersion of nanorod crystal, specific surface area and suspension stability of PAL. The ultrasonically disaggregated PAL has a higher pulping rate in water (14.96 m3/t) and saturated NaCl system (14.45 m3/t), which is significantly better than that of natural PAL in water (14.72 m3/t) and saturated NaCl solution (12.37 m3/t). It suggests that the disaggregated PAL exhibits excellent potential and adaptability as a viscosity enhancer for drilling fluid. Therefore, this work provides a feasible and efficient ultrasonic process for large-scale industrialized disaggregation of PAL crystal bundles, laying a foundation for the high-value utilization of natural PAL as one-dimensional nanomaterials.