Molybdate-Templated Luminescent Silver Alkynyl Nanoclusters: Total Structure Determination and Optical Property Analysis.

Two novel MoO42--templated luminescent silver alkynyl nanoclusters with 20-nuclearity ([(MoO42-)@Ag20(C≡CtBu)8(Ph2PO2)7(tfa)2]·(tfa-) (1)) and 18-nuclearity ([(MoO42-)@Ag18(C≡CtBu)8(Ph2PO2)7]·(OH) (2)) (tfa = trifluoroacetate) were synthesized with the green light maximum emissions at 507 and 516 nm, respectively. The nanoclusters were investigated and characterized by single-crystal X-ray crystallography, electrospray ionization mass spectrum (ESI-MS), X-ray photoelectron spectroscopy, thermogravimetry (TG), photoluminescence (PL), ultraviolet-visible (UV-vis) spectroscopy, and density functional theory calculations (DFT). The two nanoclusters differ in their structure by a supplementary [Ag2(tfa)2] organometallic surface motif, which significantly participates in the frontier molecular orbitals of 1, resulting in similar bonding patterns but different optical properties between the two clusters. Indeed, both nanoclusters show strong temperature-dependent photoluminescence properties, which make them potential candidates in the fields of optical devices for further applications.

High-resolution accurate mass approach to characterization of SCO-267 metabolites using liquid chromatography hybrid quadrupole Orbitrap mass spectrometry.

RATIONALE: SCO-267 is a potent full agonist of G-protein-coupled receptor 40. As a promising therapeutic agent for type 2 diabetes mellitus, it is necessary to elucidate its metabolite profiles during the stage of drug development for safety considerations. METHODS: The in vitro metabolism was investigated by incubating SCO-267 (5 µM) with liver microsomes and hepatocytes (rat and human). For in vivo metabolism, SCO-267 (10 mg/kg) was orally administered to rats and plasma samples were collected. The metabolites were identified via measurements of accurate mass, elemental composition and product ions using liquid chromatography coupled to hybrid quadrupole Orbitrap high-resolution mass spectrometry (LC-Orbitrap-MS). RESULTS: A total of 19 metabolites were structurally identified. M2 (hydroxyl-SCO-267), M15 (SCO-267-acyl-glucuronide), M16 (desmethyl-SCO-267) and M17 (desneopentyl-SCO-267) were verified with reference standards. M2, M11, M16 and M17 were the major metabolites originating from hydroxylation, O-demethylation and N-dealkylation, respectively. Phenotyping study with recombinant human P450 enzymes demonstrated that hydroxylation (M2 and M11) was mainly catalyzed by CYP2C8 and 3A4; demethylation (M16) was mainly catalyzed by CYP2D6, and less catalyzed by CYP2C8 and 3A4; and N-dealkylation (M17) was exclusively triggered by CYP3A4. CONCLUSIONS: Hydroxylation, O-demethylation, N-dealkylation and acyl glucuronidation were the major metabolic pathways of SCO-267. This study is the first to discover the metabolic fates of SCO-267, which provides a basis for safety assessment of this drug candidate.

Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework-Based Drug Delivery Systems.

Endophthalmitis, derived from the infections of pathogens, is a common complication during the use of ophthalmology-related biomaterials and after ophthalmic surgery. Herein, aiming at efficient photodynamic therapy (PDT) of bacterial infections and biofilm eradication of endophthalmitis, a pH-responsive zeolitic imidazolate framework-8-polyacrylic acid (ZIF-8-PAA) material is constructed for bacterial infection-targeted delivery of ammonium methylbenzene blue (MB), a broad-spectrum photosensitizer antibacterial agent. Polyacrylic acid (PAA) is incorporated into the system to achieve higher pH responsiveness and better drug loading capacity. MB-loaded ZIF-8-PAA nanoparticles are modified with AgNO3 /dopamine for in situ reduction of AgNO3 to silver nanoparticles (AgNPs), followed by a secondary modification with vancomycin/NH2 -polyethylene glycol (Van/NH2 -PEG), leading to the formation of a composite nanomaterial, ZIF-8-PAA-MB@AgNPs@Van-PEG. Dynamic light scattering, transmission electron microscopy, and UV-vis spectral analysis are used to explore the nanoparticles synthesis, drug loading and release, and related material properties. In terms of biological performance, in vitro antibacterial studies against three kinds of bacteria, i.e., Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus, suggest an obvious superiority of PDT/AgNPs to any single strategy. Both in vitro retinal pigment epithelium cellular biocompatibility experiments and in vivo mice endophthalmitis models verify the biocompatibility and antibacterial function of the composite nanomaterials.

Integration of Multiple Plasmonic and Co-Catalyst Nanostructures on TiO2 Nanosheets for Visible-Near-Infrared Photocatalytic Hydrogen Evolution.

Utilization of visible and near-infrared light has always been the pursuit of photocatalysis research. In this article, an approach is developed to integrate dual plasmonic nanostructures with TiO2 semiconductor nanosheets for photocatalytic hydrogen production in visible and near-infrared spectral regions. Specifically, the Au nanocubes and nanocages used in this work can harvest visible and near-infrared light, respectively, and generate and inject hot electrons into TiO2 . Meanwhile, Pd nanocubes that can trap the energetic electrons from TiO2 and efficiently participate in the hydrogen evolution reaction are employed as co-catalysts for improved catalytic activity. Enabled by this unique integration design, the hydrogen production rate achieved is dramatically higher than those of its counterpart structures. This work represents a step toward the rational design of semiconductor-metal hybrid structures for broad-spectrum photocatalysis.

Ligand effects in photoluminescence of copper nanoclusters.

Copper nanoclusters have attracted significant interest in the field of materials science due to their high abundance, complex structure, and unique properties. However, there is a limited amount of research on the relationship between structure and properties. In this study, we synthesized and comprehensively characterized two new Cu9 nanoclusters, [Cu9(PhSe)6(PPh2O2)3] (Cu9-1) and [Cu9(CH3OPhS)6(PPh2O2)3] (Cu9-2), in order to investigate the effect of ligands on photoluminescence. Both clusters have the same metal skeleton and similar distribution of ligands, with the only difference being the surface ligands (PhSe vs. CH3OPhS). Interestingly, the photoluminescence lifetime of Cu9-2 was found to be 3.2 times longer than that of Cu9-1. Furthermore, a notable Stokes shift (ST) was observed in the emission spectra of the two clusters. Single-crystal X-ray analysis revealed the formation of hydrogen bonds between neighboring clusters of Cu9-2, which influenced intramolecular interactions. Additionally, the methoxy groups in Cu9-2, acting as conjugated electron donors, promoted intramolecular charge transfer and π-π interaction. This study is expected to inspire further research on surface ligand engineering for controlling the properties of copper nanoclusters beyond photoluminescence.

The impact of dioctyl phthalate exposure on multiple organ systems and gut microbiota in mice.

Dioctyl phthalate, commonly known as bis(2-ethylhexyl) phthalate (DEHP), is a widely used plasticizer in various industries and has been shown to directly or indirectly impact human health. However, there is a lack of comprehensive studies evaluating the potential health risks associated with DEHP accumulation in different organs across various age groups. This study aimed to assess the effects of low (50 mg/kg·bw) and high (500 mg/kg·bw) doses of DEHP on five different organs in mice at young (4-week-old) and aged (76-week-old) life stages. Our findings revealed that both low and high doses of DEHP exposure led to significant dose-dependent inflammation in the liver, spleen, and kidney. Furthermore, regardless of age, DEHP exposure resulted in elevated activity of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the liver, as well as increased levels of creatinine (Cr) and urea in the kidney. Moreover, analysis of the fecal microbiota using 16S rRNA sequencing demonstrated that DEHP exposure disrupted the homeostasis of the gut microbiota, characterized by an increased abundance of pathogenic bacteria such as Desulfovibrio and Muribaculum, and a decreased abundance of beneficial bacteria like Lactobacillus. This study provides compelling evidence that DEHP at different concentrations can induce damage to multiple organs and disrupt gut microbiota composition. These findings lay the groundwork for further investigations into DEHP toxicity in various human organs, contributing to a better understanding of the potential health risks associated with DEHP exposure.

Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma.

BACKGROUND: Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status. METHODS: 376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis. RESULTS: We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0, and TRG0-1N+ were not reached, whereas these of patients with TRG2-3N+ were 17.37 months (95% CI, 14.14-20.60 months) and 39.97 months (95% CI, 27.05-52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi-squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%). CONCLUSION: Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.

In Situ Raman Study of Voltage Tolerance Up to 2.2 V of Ionic Liquid Analogue Supercapacitor Electrolytes Immune to Water Adsorption Conferred by Amphoteric Imidazole Additives.

Ionic liquid analogues (ILAs) are promising electrolytes for supercapacitors due to their low cost and considerable voltage (>2.0 V). However, the voltage is <1.1 V for water-adsorbed ILAs. Herein for the first time, an amphoteric imidazole (IMZ) additive is reported to address this concern by reconfiguring the solvent shell of ILAs. Addition of only 2 wt % IMZ increases the voltage from 1.1 to 2.2 V, with an increase in capacitance from 178 to 211 F g-1 and an increase in energy density from 6.8 to 32.6 Wh kg-1. In situ Raman reveals that the strong H-bonds formed by IMZ with completive ligands 1,3-propanediol and water induce a reversal of the polarity of the solvent shells, suppressing absorbed water electrochemical activity and thus increasing the voltage. This study solves the problem of low voltage for water-adsorbed ILAs and reduces the equipment cost of ILA-based supercapacitor assembly (e.g., assembly in air without a glovebox).

Hydrogen Bond Interaction in the Trade-Off Between Electrolyte Voltage Window and Supercapacitor Low-Temperature Performances.

Liquid electrolyte determines the voltage window and extreme working temperature of supercapacitors. However, the effect of weak interaction between electrolyte species on voltage window and low-temperature capacitive performance is unclear. Herein, an electrolyte model system with increasing H-bond interaction was constructed to clarify this concern. The results indicated that strong H-bond interaction was positively correlated with the number of hydroxyls, which was beneficial to expand voltage window, but deteriorated rate performance; weak H-bond improved low-temperature performance. Supercapacitors with an optimized electrolyte presented high voltage and good low-temperature performance; even at -40 °C, the maximum energy density could be maintained at 7.0 Wh kg-1 (>80 % retention relative to at -20 °C). This study revealed the mechanism of the influence of the H-bonds on electrolyte voltage window and anti-freezing capability and provided a new insight for the design of electrolytes with both high working voltage and low-temperature performance.

Ferroelectric benzimidazole additive-induced interfacial water confinement for stable 2.2 V supercapacitor electrolytes exposed to air.

Deep eutectic solvents (DESs) are known as low-cost and environmentally friendly electrolytes for supercapacitors. However, because DESs are particularly vulnerable to moisture adsorption in the air, the voltage window (<1.2 V) is significantly lower than expected. Herein, we report a new ferroelectric benzimidazole (BI) additive that, by restricting water electrochemical activity at the DES/carbon electrode interface, allows air-exposed DESs to reach a high voltage of 2.2 V. The optimized DES with 0.5 wt% BI addition not only increases the voltage but also the capacitance and energy density while maintaining excellent cycling stability. This study addresses the voltage drop of DESs in air, providing insights into the design of additives that inhibit interfacial water splitting.

Killing three birds with one stone: Near-infrared light triggered nitric oxide release for enhanced photodynamic and anti-inflammatory therapy in refractory keratitis.

Stubborn resistant bacteria, bacterial biofilms and severe inflammation are challenging issues in refractory keratitis treatment. Herein, we design a multifunctional near-infrared light-responsive nanoplatform for efficient therapy of refractory keratitis based on a "three-birds-with-one-stone" strategy, which integrates the bacteria targeting photodynamic therapy, nitric oxide (NO) sterilization, and NO-mediated anti-inflammatory property into one system. This nanoplatform (UCNANs) is constructed using the dual-emissive upconversion nanoparticles (UCNPs) as cores coated with mesoporous silica for the loading of photosensitizers with aggregation-induced emission (AIE) property and the grafting of NO donors and bacteria targeting molecules. Upon irradiation of 808 nm light, UCNPs simultaneously produce UV emission and visible emission to trigger NO release and reactive oxygen species (ROS) such as superoxide radical (O2•-) generation. Furthermore, O2•- resulting from PDT can react with NO to yield powerful oxidizing and nitrating agent peroxynitrite (ONOO-). The three components work synergistically to enhance the antibacterial outcome confirmed by in vitro and in vivo tests. The short-distance light excitation and excitation light absorption are important reasons for reducing the toxicity of materials, especially ultraviolet light damage. Moreover, bacteria elimination reduced endotoxin secretion and the released NO simultaneously inhibit the NF-κB pathways by regulating the expression of toll-like receptor 2 (TRL2) and tumor necrosis factor-α (TNF-α), which significantly relieves the inflammation of cornea. Given its excellent antibacterial and anti-inflammatory properties, UCNANs provides a competitive strategy for refractory keratitis therapy.

Photosensitizer-Loaded Multifunctional Chitosan Nanoparticles for Simultaneous in Situ Imaging, Highly Efficient Bacterial Biofilm Eradication, and Tumor Ablation.

In recent decades, bacterial and viral infections and chronic inflammatory response have emerged as important causes of cancer. Also, infections remain a significant cause of morbidity and mortality in cancer patients. In this work, carboxymethyl chitosan nanoparticles (CMC NPs) were synthesized in a facile and green way and further combined with ammonium methylbenzene blue (MB) as a cross-linking agent as well as a fluorescent molecule and a photosensitizer for self-imaging photodynamic therapy (PDT). The obtained CMC-MB NPs exhibited an apparent pH-responsive release behavior of MB, which was released for a prolonged period in a simulated physiological environment (pH 7.4) for more than 15 days and the time reduced to only 3.5 h in acidic conditions (pH 5.5). When irradiated by a 650 nm laser at 202 mW/cm2 for 5 min, the CMC-MB NPs showed efficient bactericidal and biofilm eradication properties as well as suppression of tumor cell growth in a similar acidified microenvironment. Furthermore, in an in vivo rabbit wound bacterial infection model, the rapid sterilization of CMC-MB NPs played a crucial role in bacterial infections, inflammation inhibition, and wound healing. As a PDT treatment against cancer, the CMC-MB NPs also exhibited an efficient antitumor therapeutic effect in a subcutaneous tumor mice model.

Design of smart targeted and responsive drug delivery systems with enhanced antibacterial properties.

The use of antibiotics has been an epoch-making invention in the past few decades for the treatment of infectious diseases. However, the intravenous injection of antibiotics lacking responsiveness and targeting properties has led to low drug utilization and high cytotoxicity. More importantly, it has also caused the development and spread of drug-resistant bacteria due to repeated medication and increased dosage. The differences in the microenvironments of the bacterial infection sites and normal tissues, such as lower pH, high expression of some special enzymes, hydrogen peroxide and released toxins, etc., are usually used for targeted and controlled drug delivery. In addition, bacterial surface charges, antigens and the surface structures of bacterial cell walls are all different from normal tissue cells. Based on the special bacterial infection microenvironments and bacteria surface properties, a series of drug delivery systems has been constructed for highly efficient drug release. This review summarizes the recent progress in targeted and responsive drug delivery systems for enhanced antibacterial properties.

Facet engineered interface design of NaYF4:Yb,Tm upconversion nanocrystals on BiOCl nanoplates for enhanced near-infrared photocatalysis.

The combination of upconversion nanocrystals with a wide-bandgap semiconductor is an efficient strategy to develop near-infrared (NIR)-responsive photocatalysts. The photocatalytic activity of the hybrid structures is greatly determined by the efficiency of the energy transfer on the interface between upconversion nanocrystals and the semiconductor. In this work, we demonstrate the interface design of a NaYF4:Yb,Tm-BiOCl hybrid structure based on the choice of suitable BiOCl facets in depositing NaYF4:Yb,Tm upconversion nanocrystals. It was found that the selective deposition of NaYF4:Yb,Tm nanocrystals on the BiOCl(110) facet can greatly enhance the photocatalytic performance in dye degradation compared with the sample with NaYF4:Yb,Tm nanocrystals loaded on the BiOCl(001) facet. Two effects were believed to contribute to this enhancement: (1) a stronger UV emission absorption ability of the BiOCl(110) facet from NaYF4:Yb,Tm in generating more photo-induced charge carriers resulted from the narrower bandgap; (2) a shorter diffusion distance of photogenerated charge carriers to the BiOCl(110) reactive facet for surface catalytic reactions owing to the spatial charge separation between different facets. This work highlights the rational interfacial design of an upconversion nanocrystal-semiconductor hybrid structure for enhanced energy transfer in photocatalysis.

[Comparative study of serum levels of BMP-2 and heterotopic ossification in traumatic brain injury and fractures patients].

OBJECTIVE: To investigate the relationship between serum level of bone morphogenetic proteins-2 (BMP-2) and heterotopic ossification (HO) in traumatic brain injury (TBI) and fractures patients, providing the theoretical evidence for the clinical prevention of HO. METHODS: From December 2007 to January 2009, 145 with trama patients were selected. There were 96 closed primary traumatic brain injury patients, 1 penetrating primary traumatic brain injury, 29 fractures of the radius and ulna, 11 fractures of the humerus, 32 fractures of the tibia and fibula, 27 fractures of the femur. All patients were divided into three groups (i.e., group A, group B and group C) by the type of fracture. Fifty-seven patients in group A (TBI only), including 37 males and 20 females, ranged in the age from 29 to 61 years, with an average age of (43.91 +/- 11.09) years. The disease course was from 13 to 67 d, with an average duration of (18.96 +/- 10.46) d. Forty-eight patients in group B (fractures only), 25 males and 23 females, ranged in age from 31 to 54 years, with an average age of (41.73 +/- 8.41) years. The disease course was from 6 to 48 d, with an average duration of (16.02 +/- 8.71) d. Forty patients in group C (TBI combined with extremities fractures), including 23 males and 17 females, ranged in age from 30 to 60 years, with an average age of (45.87 +/- 14.15) years. The disease course was from 18 to 76 d, with an average of (21.28 +/- 13.02) d. Thirty-one extremities fractures with no significant separations or displacements of fragments were treated with traction reductions, cast immobilization or splint fixations. Sixty-eight fractures with significant separations and displacements of fragments were treated with intramedullary nail fixations or screw internal fixations. Sixty-three TBI patients were treated with open-skull surgeries immediately while 34 TBI patients were treated with stanching bleeding, reducing intracranial pressure and improving cerebral blood circulation. All patients were also divided into two groups (group D and group E) according to the 14-to 16-month follow-up X-ray film results. Seventeen patients in group D (HO had been found), including 11 males and 6 females, ranged in age from 29 to 55 years old, with an average age of (46.88 +/- 7.13) years. The disease course was from 6 to 30 d, with an average of (20.18 +/- 9.78) d. All 128 patients in group E (HO had been not found), including 74 males and 54 females, ranged in age from 33 to 61 years, with an average age of (43.31 +/- 12.94) years. The disease course was from 15 to 76 d, with an average of (18.42 +/- 11.58) d. The 49 subjects in group F (normal controls), 29 males and 20 females, ranged in age from 31 to 60 years, average (43.50 +/- 14.40) years. Peripheral blood samples were taken for the determination of BMP-2 in blood serum on 0.5, 3, 15 d and 30 d after fractures by enzyme-linked immunosorbent assay (ELISA). Analysis of variance and least significant difference test were done with the help of SPSS 13.0 statistic software. RESULTS: The incidence rates of HO between the TBI only patients (21.05%, 12/57) and the fractures only patients(4.17%, 2/48) were significant different (chi2=5.05, P<0.05). Serum levels of BMP-2 at 0.5, 3 d and 15 d between group A and group B were significant different. Serum levels of BMP-2 at 0.5, 3, 15 d and 30 d between group D and group E were significant different. Serum levels of BMP-2 at each time in each group were higher than the control group (51.30 +/- 23.41 ng/L) (P<0.01). CONCLUSION: High serum levels of BMP-2 in TBI only group is one of factors in causing HO. Serum level of BMP-2 at 15 d since fractures may be the obvervational index of HO prevention.