Ultrasmall copper nanoclusters as an efficient antibacterial agent for primary peritonitis therapy.

The urgent need to develop biocompatible, non-resistant antibacterial agents to effectively combat Gram-negative bacterial infections, particularly for the treatment of peritonitis, presents a significant challenge. In this study, we introduce our water-soluble Cu30 nanoclusters (NCs) as a potent and versatile antibacterial agent tailored for addressing peritonitis. The as-synthesized atomically precise Cu30 NCs demonstrate exceptional broad-spectrum antibacterial performance, and especially outstanding bactericidal activity of 100% against Gram-negative Escherichia coli (E. coli). Our in vivo experimental findings indicate that the Cu30 NCs exhibit remarkable therapeutic efficacy against primary peritonitis caused by E. coli infection. Specifically, the treatment leads to a profound reduction of drug-resistant bacteria in the peritoneal cavity of mice with peritonitis by more than 5 orders of magnitude, along with the resolution of pathological features in the peritoneum and spleen. Additionally, comprehensive in vivo biosafety assessment underscores the remarkable biocompatibility, low biotoxicity, as well as efficient hepatic and renal clearance of Cu30 NCs, emphasizing their potential for in vivo application. This investigation is poised to advance the development of novel Cu NC-based antibacterial agents for in vivo antibacterial treatment and the elimination of abdominal inflammation.

Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis.

Cornus officinalis, a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis, both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl4, while in vitro HSCs were exposed to transforming growth factor-ß (TGF-ß). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl4-induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and Sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. siRNA experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

SIRT3: A potential therapeutic target for liver fibrosis.

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.

Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.

Low-current-density stability of vanadium-based cathodes for aqueous zinc-ion batteries.

Vanadium-based cathodes have received widespread attention in the field of aqueous zinc-ion batteries, presenting a promising prospect for stationary energy storage applications. However, the rapid capacity decay at low current densities has hampered their development. In particular, capacity stability at low current densities is a requisite in numerous practical applications, typically encompassing peak load regulation of the electricity grid, household energy storage systems, and uninterrupted power supplies. Despite possessing notably high specific capacities, vanadium-based materials exhibit severe instability at low current densities. Moreover, the issue of stabilizing electrode reactions at these densities for vanadium-based materials has been explored insufficiently in existing research. This review aims to investigate the matter of stability in vanadium-based materials at low current densities by concentrating on the mechanisms of capacity fading and optimization strategies. It proposes a comprehensive approach that includes electrolyte optimization, electrode modulation, and electrochemical operational conditions. Finally, we presented several crucial prospects for advancing the practical development of vanadium-based aqueous zinc-ion batteries.

Farnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis.

The farnesoid X receptor (FXR), a ligand-activated transcription factor, plays a crucial role in regulating bile acid metabolism within the enterohepatic circulation. Beyond its involvement in metabolic disorders and immune imbalances affecting various tissues, FXR is implicated in microbiota modulation, gut- to-brain communication, and liver disease. The liver, as a pivotal metabolic and detoxification organ, is susceptible to damage from factors such as alcohol, viruses, drugs, and high-fat diets. Chronic or recurrent liver injury can culminate in liver fibrosis, which, if left untreated, may progress to cirrhosis and even liver cancer, posing significant health risks. However, therapeutic options for liver fibrosis remain limited in terms of FDA- approved drugs. Recent insights into the structure of FXR, coupled with animal and clinical investigations, have shed light on its potential pharmacological role in hepatic fibrosis. Progress has been achieved in both fundamental research and clinical applications. This review critically examines recent advancements in FXR research, highlighting challenges and potential mechanisms underlying its role in liver fibrosis treatment.

Conjugating AIE-featured AuAg nanoclusters with highly luminescent carbon dots for improved visible-light-driven antibacterial activity.

Metal nanoclusters (NCs) have emerged as novel antibacterial agents featuring broad-spectrum antibacterial activity without drug resistance for bacteria, but suffer from fast antibacterial invalidation due to their consumption by bacteria. Herein we report the design of a visible-light-driven photodynamic antibacterial agent based on conjugating aggregation-induced emission (AIE)-featured AuAg NCs with highly luminescent carbon dots (CDs). The conjugation of CDs with AuAg NCs could not only enhance the visible-light harvest, but also promote charge carrier generation/separation via charge/energy transfer, leading to the production of abundant reactive oxygen species (ROS) for bacterial killing under visible-light irradiation. Consequently, the as-obtained CDs@AuAg NCs display excellent photodynamic antibacterial activity against both Gram-positive and Gram-negative bacteria with 4-5 orders of magnitude reduction in colony forming units, which is different from the conventional metal NC-based analogue relying on self-consumption for bacterial killing. In addition, the CDs@AuAg NCs are found to be free of cytotoxicity; the ROS capture experiments indicate that the photoproduced H2O2 by CDs@AuAg NCs is the main active species for bacterial killing, accounting for nearly 48% of the total antibacterial efficacy. This study provides a paradigm for the design of metal NC-based photodynamic antibacterial agents for diverse bactericidal applications.

Layered double hydroxide coated electrospun carbon nanofibers as the chloride capturing electrode for ultrafast electrochemical deionization.

Slow desalination kinetics and poor durability of the electrodes are two key limitations of electrochemical deionization (EDI) that are considered to be the next generation of capacitive desalination (CDI). Herein, we report the design of a high-efficiency chloride removal electrode material for accelerating the desalination kinetics and concurrently improving the durability of EDI, which is based on coating NiMn-Cl layered double hydroxides (LDHs) on the surface of electrospun carbon nanofibers (CNFs@LDHs). The salient features of the as-developed CNFs@LDHs are that applying layer-structured LDHs with abundant redox-active sites to accelerate the pseudo-capacitive ion storage via fast ion intercalation/deintercalation, and leveraging the rigid CNF backbone to strengthen its durability by preventing the potential aggregation of LDHs. As expected, the CNFs@LDH based EDI system displays an ultrafast desalination rate of 0.51 mg g-1 s-1 and outstanding long-term stability (only 10.66 % desalination capacity reduction after 35 cycles), which is achieved without sacrificing its excellent desalination capacity (72.04 mg g-1). This work could be inspirational for the future design of ultrafast yet durable EDI approaching industrial desalination applications.

Bismuth oxychloride nanostructure coated carbon sponge as flow-through electrode for highly efficient rocking-chair capacitive deionization.

Rocking-chair capacitive deionization (RCDI), as the next generation technique of capacitive deionization, has thrived to be one of the most promising strategies in the desalination community, yet was hindered mostly by its relatively low desalination rate and stability. Motivated by the goal of simultaneously enhancing the desalination rate and structural stability of the electrode, this paper reports an anion-driven flow-through RCDI (AFT-RCDI) system equipped with BiOCl nanostructure coated carbon sponge (CS@BiOCl for short; its backbone is derived from commercially available melamine foam with minimum capital cost) as the flow-through electrode. Owning to the rational design of the composite electrode material with minimum charge transfer resistance and ultrahigh structure stability as well as the superior flow-through cell architecture, the AFT-RCDI displays excellent desalination performance (desalination capacity up to 107.33 mg g-1; desalination rate up to 0.53 mg g-1s-1) with superior long-term stability (91.75% desalination capacity remained after 30 cycles). This work provides a new thought of coupling anion capturing electrode with flow-through cell architecture and employing a low-cost CS@BiOCl electrode with commercially available backbone material, which could shed light on the further development of low-cost electrochemical desalination systems.

Fluorescent Egg White-Based Carbon Dots as a High-Sensitivity Iron Chelator for the Therapy of Nonalcoholic Fatty Liver Disease by Iron Overload in Zebrafish.

Iron overload is the direct cause of many ferroptosis diseases, and it is essential to maintain iron homeostasis. In this paper, we report the Fe3+ chelation and therapy of the iron overload nonalcoholic fatty liver disease (NAFLD) by the fluorescent egg white-based carbon dots (EWCDs) obtained through the microwave-assisted pyrolysis method. As a high-sensitivity sensor, EWCDs show a high correlation between fluorescence emission and the concentration of Fe3+ (R2 = 0.993) in low concentration ranges of 0-25 µM. In vivo and in vitro, the EWCDs show characteristics of high biocompatibility and specific binding of Fe3+. As a novel type of the nano-iron-chelator, EWCDs can successfully attenuate the production of lethal reactive oxygen species. EWCDs not only alleviate the endoplasmic reticulum stress response but also regulate the NF-κB signaling pathway downstream of the Nrf2 signaling pathway. EWCDs prevent hepatocyte apoptosis, regulate fatty acid metabolism, and alleviate inflammation. Ultimately, they alleviate NAFLD induced by iron overload in zebrafish. This work may provide a new idea and method for the application of carbon dots in the field of disease detection and treatment.

Mechanistic insights into the two-phase synthesis of heteroleptic Au nanoclusters.

A mechanistic study on the two-phase synthesis of heteroleptic Au nanoclusters (NCs) is reported here. First, the effects of binary ligands on controlling the size of Au NCs were examined: (1) the binary ligands could exhibit an eclectic effect on the size control of Au NCs if the binding affinities of such hetero-ligands with Au are comparable and (2) the binary ligands could exhibit a competitive effect on the size control of Au NCs, and the size of the Au NCs could be determined by the ligand with stronger binding affinity to Au. This finding is interesting and can shed some light on the design of new functional metal NCs. Secondly, the formation mechanism of the heteroleptic Au NCs that originated from the complex precursors was unprecedentedly studied. The complex precursors of the heteroleptic Au NCs were identified to be the predominant hybridized ligand#1-Au(i)-ligand#2 species, which is helpful for understanding the synthetic mechanisms in depth. Moreover, the growth processes of the heteroleptic Au NCs were also monitored, and some fundamental perceptions about the growth pathway and the structures of the Au NCs were obtained.

From understanding the roles of tetraoctylammonium bromide in the two-phase Brust-Schiffrin method to tuning the size of gold nanoclusters.

The two-phase Brust-Schiffrin (B-S) method has been widely used for synthesizing small-sized Au nanoparticles (NPs) of size 2-6 nm, as well as Au nanoclusters (NCs) of size <2 nm. However, size tuning of Au NCs at the atomic level by this method is challenging probably due to a lack of in-depth understanding of its mechanism. Herein, we report the identification of two roles of tetraoctylammonium bromide (TOAB) in the two-phase B-S method: TOAB not only transfers Au(iii) precursors but also transfers the reducing agent NaBH4 from the aqueous to the organic phase. On this basis, we developed a novel two-phase synthetic strategy by decoupling the roles of the TOAB: (1) using the hydrophobic selenolate ligand to transfer Au(iii) precursors from the aqueous to the organic phase via the formation of selenolate-Au(i) complexes and (2) deploying a small amount of TOAB as "shuttles" to transfer NaBH4 into the organic phase for controlled reduction of selenolate-Au(i) complexes in organic phase. Using this strategy, size tuning of Au NCs at the atomic level could be achieved by simply varying the amount of TOAB. The high yields of Au NCs (≥76%) together with the short synthetic time (≤3 h) and size-tuning capability further illustrate the attractiveness of this synthetic strategy. These advantages also present the classical B-S method with greater strength and flexibility towards NC synthesis.

Water-soluble metal nanoclusters: recent advances in molecular-level exploration and biomedical applications.

Water-soluble metal nanoclusters (MNCs) have received extraordinary attention in both fundamental and applied fields due to their ultrasmall size, unique molecular-like properties, rich surface chemistry, benign biocompatibility, and good stability. Currently, the state-of-the-art research on water-soluble MNCs has been upgraded from the nanoscale to the molecular level especially in the following aspects: (1) synthesis of highly luminescent MNCs featuring aggregation-induced emission (AIE), (2) Engineering the ligand shell of MNCs for controllable surface chemistry and (3) Tracking the reductive growth process of MNCs. Such molecular-level research progress of water-soluble MNCs in turn facilitated their development in biomedical applications. In this Frontier Article, we start our discussion by briefly summarizing the recent molecular-level research progress of water-soluble MNCs in the above-mentioned three aspects, followed by our perspectives on these fundamental aspects. Afterwards, the latest advance in biomedical applications of water-soluble MNCs is discussed. We hope that this Frontier Article could stimulate more studies on the molecular- or atomic-level understanding and biomedical applications of water-soluble MNCs.

Facile synthesis of water-soluble Au(25-x)Ag(x) nanoclusters protected by mono- and bi-thiolate ligands.

A series of water-soluble Au25-xAgx nanoclusters (NCs) protected by mono- and bi-thiolate ligands are synthesized via the NaOH-mediated NaBH4 reduction method. Compositions of both the metal core and the ligand shell can be tailored by varying the feeding ratios of metal precursors and hetero-ligands, further enriching the functionalities of the NCs.

Lighting up thiolated Au@Ag nanoclusters via aggregation-induced emission.

A simple strategy has been developed to synthesize highly luminescent thiolated Au@Ag nanoclusters (NCs) by using Ag(i) ions to bridge small Au(i)-thiolate motifs on the weakly luminescent thiolated Au NCs, leading to the formation of large Au(i)/Ag(i)-thiolate motifs on the NC surface and thus generating strong luminescence via aggregation-induced emission.

Glutathione-protected silver nanoclusters as cysteine-selective fluorometric and colorimetric probe.

The integration of the unique thiol-Ag chemistry and the specific steric hindrance from the organic layer of fluorescent Ag nanoclusters (AgNCs) was first developed in this work to achieve a simple detection of cysteine (Cys) with high selectivity and sensitivity. The key design is a strongly red-emitting AgNC protected by the interference biothiol, glutathione, or GSH (hereafter referred to as GSH-AgNCs), where both the physicochemical properties (Ag surface chemistry and fluorescence) of the NC core and the physical properties (e.g., steric hindrance) of the organic shell were fully utilized for Cys detection with three major features. First, owing to the specific thiol-Ag interaction, the fluorescent GSH-AgNCs showed superior selectivity for Cys over the other 19 natural amino acids (nonthiol-containing). Second, the GSH protecting layer on the NC surface made possible the differentiation of Cys from GSH (or other large-sized thiol molecules) simply by their size. Third, the ultrasmall size of GSH-AgNCs and the high affinity of the thiol-Ag interaction provided high sensitivity for Cys detection with a detection limit of <3 nM. The assay developed in this study is of interest not only because it provides a simple Cys sensor with high selectivity and sensitivity but also because it exemplifies the utilization of the physical properties of organic ligands on the nanomaterial surface to further improve the sensor performance, which could open a new design strategy for other sensor development.

Traveling through the Desalting Column Spontaneously Transforms Thiolated Ag Nanoclusters from Nonluminescent to Highly Luminescent.

This letter reports an unexpected observation in the purification of ultrasmall (<2 nm) thiolate-protected Ag nanoclusters (NCs) via a common separation technique (e.g., desalting column and ultrafiltration), where the nonluminescent Ag NCs were spontaneously transformed to highly luminescent NCs during the separation. This interesting finding was then used to develop a facile and fast (<5 min) synthesis method for highly luminescent Ag NCs. The key strategy was to use the separation process to selectively remove small species (e.g., salts and excess protecting ligands) from the Ag NC solution, which induced a size or structure-focusing of Ag NCs in the solution, leading to the formation of highly luminescent Ag NCs. The concurrent synthesis and purification of highly luminescent Ag NCs via a common "physical separation unit" could be further advanced in a continuous mode for large-scale production of luminescent Ag NCs.