Spatially confined dual-emission nanoprobes assembled from silicon nanoparticles and gold nanoclusters for ratiometric biosensing.

Gold nanoclusters (AuNCs) possess weak intrinsic fluorescence, limiting their sensitivity in biosensing applications. This study addresses these limitations by developing a spatially confined dual-emission nanoprobe composed of silicon nanoparticles (SiNPs) and AuNCs. This amplified and stabilized fluorescence mechanism overcomes the limitations associated with using AuNCs alone, achieving superior sensitivity in the sensing platform. The nanoprobe was successfully employed for ratiometric detection of bleomycin (BLM) in serum samples, operating at an excitation wavelength of 365 nm, with emission wavelengths at 480 nm and 580 nm. The analytical performance of the system is distinguished by a linear detection range of 0-3.5 µM, an impressive limit of detection (LOD) of 35.27 nM, and exceptional recoveries ranging from 96.80 to 105.9%. This innovative approach significantly enhances the applicability and reliability of AuNC-based biosensing in complex biological media, highlighting its superior analytical capabilities.

Gold Nanoclusters whose Photoluminescent Properties are Dynamically Tunable by Modulating the Assembly Pathway Complexity.

Modulating the assembly pathway is an indispensable strategy for optimizing the performance of optical materials. However, implementing this strategy is nontrivial for metal nanocluster building blocks, due to the limited functional modification of nanoclusters and complexity of their emission mechanism. In this report, we demonstrate that a gold nanocluster modified by 4,6-diamino-2-pyrimidinethiol (DPT-AuNCs) self-assembles into two distinct aggregation structures in methanol (MeOH)/water mixed solvent, thus exhibiting pathway complexity. Kinetic studies show that DPT-AuNCs firstly assembles into non-luminescent nanofibers (kinetically controlled), which further transforms into strongly luminescent microflowers (thermodynamicallycontrolled). In-depth analysis of the assembly mechanism reveals that the transformation of aggregation structures involves the disassembly of nanofibers and a subsequent nucleation-growth process. Temperature-dependent photoluminescence (PL) spectroscopy and infrared (IR) measurements reveal that inter-cluster hydrogen bonding bridged by solvent molecules and C-H···π interaction are the key factors for emission enhancement. The photoluminescent property of DPT-AuNCs can be controlled by varying the cosolvent in water, enabling DPT-AuNCs to distinguish different kind of alcohols, particularly the isomerism n-propanol (NPA) and isopropanol (IPA). Additionally, he addition of seeds effectively regulate the assembly kinetics of DPT-AuNCs. This study advances our understanding of assembly pathways and improves the luminescent performance of nanoclusters (NCs).

Backbone-Enabled and Ester Groups Switched δ-C(sp2)-H Amination/Fluorination: Cyclic Dipeptides Synthesis.

An efficient and concise strategy for the synthesis of cyclic dipeptides via Pd-catalyzed site-selective δ-C(sp2)-H amination/fluorination and N-to-C cyclization is disclosed. The backbone amides within the dipeptides serves as endogenous directing groups, while the desired products were switched by the C-terminal ester group. This chemistry presents a novel and robust alternative to construct cyclodipeptide fragments.

Tandem Four-Component Reaction to Access Fused Polycycles Exhibiting Aggregation-Enhanced Through-Space Charge Transfer Emission.

Rapid construction of new fluorescence emitters is essential in advancing synthetic luminescent materials. This study illustrated a piperidine-promoted reaction of chiral dialdehyde with benzoylacetonitrile and malonitrile, leading to the formation of the 6/6/7 fused cyclic product in good yield. The proposed reaction mechanism involves a dual condensation/cyclization process, achieving the formation of up to six bonds for fused polycycles. The single crystal structure analysis revealed that the fused cyclic skeleton contains face-to-face naphthyl and cyanoalkenyl motifs, which act as the electronic donor and acceptor, respectively, potentially resulting in through-space charge transfer (TSCT) emission. While the TSCT emissions were weak in solution, a notable increase in luminescence intensity was observed upon aggregation, indicating bright fluorescent light. A series of theoretical analyses further supported the possibility of spatial electronic communication based on frontier molecular orbitals, the distance of charge transfer, and reduced density gradient analysis. This work not only provides guidance for the one-step synthesis of complex polycycles, but also offers valuable insights into the design of aggregation-enhanced TSCT emission materials.

Water bridges as the trigger in an amino functionalized Zn-MOF for highly selective and sensitive fluorescent sensing of water.

Water is a fundamental element for life. The highly selective and sensitive sensing of water is always attractive for mankind in activities such as physiological processes study and extraterrestrial life exploration. Fluorescent MOFs with precise channels and functional groups might specifically recognize water molecules with hydrogen-bond interaction or coordination effects and work as water sensors. As a proof of concept, herein, an amino functionalized Zn-MOF (named as complex 1) with pores that just right for water molecules to form hydrogen bond bridges is revealed for highly selective and sensitive fluorescent sensing of water. The single-crystal X-ray diffraction analysis indicates that the 3D framework of complex 1 is functionalized with free amino groups in the channels. Hydrogen bonds formed in the channel along b-axis as water bridges to connect two adjacent NH2bdc ligands and result in the restriction of intramolecular motions (RIM) which could responsible for the selective turn-on fluorescence response to water. Complex 1 exhibits high sensitive to trace amount of water in organic solvents and could be used for water detection in a wide range water contents. Take advantages of complex 1, portable sensors (complex 1@PMMA) were prepared and used in the highly sensitive water sensing.

Backbone-enabled modification of peptides with benzoquinone via palladium-catalyzed δ-C(sp2)-H functionalization.

Backbone-enabled site-selective modification of peptides with benzoquinone via Pd-catalyzed δ-C(sp2)-H functionalization has been achieved. The amide groups of peptides serve as internal directional groups, facilitating C-H functionalization through a kinetically less favored six-membered palladacycle. This methodology presents novel opportunities for the late-stage site-selective diversification of peptides.

Relay Copper-Catalyzed Synthesis of Imidazo[1,5-a]pyridine Scaffolds from Phenylalanine and Halohydrocarbon.

An efficient and straightforward strategy to synthesize imidazo[1,5-a]pyridine compounds from phenylalanine and halohydrocarbon has been successfully developed. The protocol features a relay copper-catalyzed reaction involving intermolecular C-O coupling and intramolecular C-N cyclization, providing an approach to access a diverse range of imidazo[1,5-a]pyridine derivatives with unique aza quaternary carbon centers.

Responsive calcium-derived nanoassemblies induce mitochondrial disorder to promote tumor calcification.

Physiological calcification of the treated tumor area is considered to be a predictor of good prognosis. Promoting tumor calcification by inducing mitochondrial metabolic disorder and destroying calcium equilibrium has a potential inhibitory effect on tumor proliferation. Here, by promoting calcification by inducing mitochondrial dysfunction combined with triggering a surge of reactive oxygen species, we construct a bioresponsive calcification initiator, termed CaP-AA, using CaHPO4 covalently doped l-ascorbic acid. CaHPO4 releases Ca2+ within the cytoplasm of tumor cells to trigger calcium overload. Meanwhile, exogenous l-ascorbic acid indirectly enhances metabolic balance disruption via pro-oxidant effects. Such Ca2+ overload increases the likelihood of tumor calcification in vivo for tumor inhibition by perturbing mitochondrial homeostasis. The introduction of responsive calcium sources that would, in turn, trigger intratumoral calcification mediated by perturbing mitochondrial homeostasis would be an effective regulatory strategy for tumor therapy.

Late-Stage Diversification of Peptides via Pd-Catalyzed Site-Selective δ-C(sp2)-H Fluorination and Amination.

Site-selective C-H fluorination is an attractive strategy for directly transforming inert C-H bonds into C-F bonds, yet it remains a significant challenge. Herein, we have developed an efficient and versatile strategy for site-selective fluorination and amination of phenylalanine-containing peptides via late-stage Pd-catalyzed δ-C(sp2)-H activation, providing a valuable tool for the in situ synthesis of fluorinated indoline scaffolds within peptides.

Copper-Catalyzed Chemodivergent Synthesis of Oxazoles and Imidazolidones by Selective C-O/C-N Cyclization.

Efficient synthesis of phenylalanine-derived oxazoles and imidazolidones can be achieved by copper-catalyzed reactions that are controlled by directing groups and proceed by selective C-O or C-N coupling. This strategy employs inexpensive commercial copper catalysts and readily available starting materials. It uses a convenient reaction procedure and provides a reliable approach to the versatile and flexible assembly of heterocyclic building blocks.

Site-Selective Modification of Peptides via Late-Stage Pd-Catalyzed Tandem Reaction of Phenylalanine with Benzoquinone.

An efficient and straightforward approach for site-selective functionalization of phenylalanine and phenylalanine-containing peptide via a Pd-catalyzed tandem reaction has been developed. The robust method underwent dual C-H activation, including C-C coupling with benzoquinone and intramolecular C-N cyclization, providing a feasible and rapid synthetic route to incorporate 4-benzoquinone-indoline fragments into peptides.

A Cu2+ triggered reversible photochromic system: the structure photochromic response relationship study and potential applications.

Fifteen rhodamine B hydrazide hydrazone (RhBHH) derivatives (compounds a-o) with various substituent groups at different position and their photochromic property triggered by Cu2+ were studied to illustrate the structure photochromic response relationship (SPRR). Three of them (compounds f-h) with a para-position hydroxyl group and two meta-position halogen substituents display Cu2+-triggered photochromic which is significantly different from the previous reports. It was found that halogen atoms, which were generally considered to have no remarkable regulation effect, exhibited great influences on the photochromic behaviour of RhBHH derivatives. Detail photochromic properties of the developed photochromic system were revealed by using compound g as the model substrate, and only Cu2+ displayed high selective trigger effect. Good reversible photochromic phenomenon was observed after stimulated with visible light irradiation and dark (or heat) bleaching consecutively. Furthermore, this photochromic system could be used in the preparation of photochromic glass, special security ink, molecular logic gate and two-dimensional code for security information storage.

Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.

Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.

PARP-1 Inhibition Repressed Imbalance of Th17 and Treg Cells in Preterm Rats with Intrauterine Infection-Induced Acute Respiratory Distress Syndrome by Reducing the Expression Level of IL-6.

BACKGROUND: Abundant reports have uncovered an imbalance of Treg and Th17 cells in pulmonary diseases. Hereon, we intend to explore the impact of PARP-1 on the imbalance of Th17/Treg and the potential mechanism in premature rats with acute respiratory distress syndrome (ARDS). METHODS: Preterm ARDS infants and healthy term infants were enrolled in this investigation. To induce a rat model of ARDS, E.coli suspension was given to rats through two vaginal dilator-guided intramuscular injections. H&E staining was used to perform histopathological examination. Flow cytometry was employed to assess the proportion of Th17 or Treg cells accounted for CD4+ T cells. ELISA was applied to measure levels of IL-6, IL-17A, and IL-10 in the serum of ARDS patients. Moreover, the mRNA and protein expression levels of PARP-1, IL-6, IL-17A, and IL-10 were detected through qRT-PCR and western blotting. RESULTS: An increased Th17/Treg ratio was observed in preterm infants and rats with ARDS. The PARP-1 expression level was raised in the lung tissues of ARDS rats, and PARP-1 downregulation alleviated E.coli-induced lung injury in preterm rats. Expression levels of PARP-1, IL-6, and IL-17A were raised, and the IL-10 level was reduced in the lung tissues of rats after E.coli treatment, which was all reversed by PARP-1 suppression. Importantly, the ratio of Th17/Treg differentiated from purified CD4+ T cells of the E.coli + PARP-1 inhibitor group was elevated by recombinant IL-6. CONCLUSION: PARP-1 downregulation repressed the imbalance of Th17 and Treg cells via reducing the expression level of IL-6, implying that PARP-1 may be a promising target for ARDS therapy.

A novel high sensitive Cd-MOF fluorescent probe for acetone vapor in air and picric acid in water: Synthesis, structure and sensing properties.

A novel three-dimensional luminescence Cd-MOF sensor with the molecular formula {[(CH3)2NH2]2 Cd3(ptptc)2} (complex 1) has been synthesized by using terphenyl-3,3',5,5'-tetracarboxylic acid (H4ptptc) and Cd(NO3)2·4H2O under solvothermal conditions. Single crystal X-ray diffraction analysis shows that complex 1 crystallizes in the monoclinic system C2/c space group and consists of one-dimensional channels. Complex 1 exhibits characteristic fluorescence emission (λem = 380 nm) both in solid state and solvents upon excitation at 300 nm. Real-time fluorescence quenching of complex 1 was observed in the fluorescence sensing of acetone vapor and picric acid. Intriguingly, ppm scale detection limit for acetone vapor in air and nano-mole scale detection limit for picric acid in water were observed. Moreover, good reusability and liner/nonlinear relationships were observed in the fluorescent titration.

Artesunate ameliorates sepsis-induced acute lung injury by activating the mTOR/AKT/PI3K axis.

Sepsis-induced acute lung injury (ALI) remains one of the most common disorders in hospitals. The aim of this research was to explore the underlying characteristics and mechanisms of artesunate (AS) in protecting rat lungs from sepsis. The sepsis-induced ALI model was generated in SD rats by the intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg) for 24 h. The rats were randomly assigned into 4 groups: Sham, LPS, LPS + AS, and LPS + AS + LY294002. Pathological evaluation of the lungs was conducted by HE staining, immunofluorescence, and TUNEL assay, and the MPO activity and the W/D ratio of each group were evaluated. The levels of inflammatory mediators (TNF-α and IL-6) were measured by immunoblotting, immunofluorescence and real-time PCR. Western blotting was used to determine the protein levels of PI3K, cleaved Caspase-3, p-mTOR, mTOR, p-Akt, and Akt in the lungs. The MPO activity, W/D ratio and lung injury score were obviously elevated after induction of ALI by LPS. Nevertheless, these alterations could be inhibited by AS. In addition, sepsis decreased the levels of p-mTOR, p-Akt, and PI3K and elevated the expression of cl-caspase-3, TNF-α, and IL-6 in the lungs. After AS administration, these alterations were obviously decreased, but treatment with the PI3K antagonist LY294002 inhibited the function of AS. AS could partially protect against LPS-induced ALI by inhibiting apoptosis and inflammatory mediator production, and this function is perhaps associated with the regulation of the mTOR/AKT/PI3K axis. These findings suggest that AS may possess certain beneficial characteristics in protecting the lungs from sepsis.

Protective role of microRNA-27a upregulation and HSP90 silencing against cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: MicroRNAs (miRNAs) have been reported in cerebral ischemia-reperfusion injury, yet the function of miR-27a in it has seldom been mentioned. This study aims to assess the mechanisms of miR-27a in rats with cerebral ischemia-reperfusion injury. METHODS: The cerebral ischemia-reperfusion models of rat pups were established by bilateral carotid artery occlusion. Rats were treated with miR-27a agomir, silenced HSP90 expression plasmids or PI3K/AKT/mTOR pathway agonist. Oxidative stress indices, inflammatory factors, brain tissue water content, cerebral infarct volume, neurological function score and neuronal apoptosis in rats with cerebral ischemia-reperfusion injury were measured. MiR-27a and HSP90 expression and PI3K/AKT/mTOR phosphorylation levels in the brain tissues of rats were also detected. RESULTS: MiR-27a expression and PI3K/AKT/mTOR phosphorylation levels were downregulated while HSP90 expression was upregulated in cerebral ischemia-reperfusion injury rats. Elevated miR-27a or reduced HSP90 diminished water content, neuronal apoptosis and infarct volume, suppressed oxidative stress and inflammatory response, as well as improved neurological deficits and pathological damages. Moreover, elevated miR-27a or silenced HSP90 upregulated PI3K/AKT/mTOR phosphorylation levels in cerebral ischemia-reperfusion injury rats. HSP90 silencing or PI3K/AKT/mTOR pathway agonist reversed the unfavorable effects of low miR-27a expression on cerebral ischemia-reperfusion injury rats. CONCLUSION: To conclude, our study demonstrates that elevated miR-27a or decreased HSP90 attenuates oxidative stress and inflammatory response, and improves neurological function in cerebral ischemia-reperfusion injury rats by activating PI3K/AKT/mTOR signaling pathway.

A novel rhodamine-based colorimetric and fluorometric probe for simultaneous detection of multi-metal ions.

Effective and simultaneous detection of multi-metal ions has been achieved by a colorimetric and fluorometric probe (REHBA) synthesized from rhodamine hydrazide and polyhydroxyl aromatic aldehyde. REHBA can serve as a colorimetric detector for Cu2+ and Co2+, and a fluorometric probe for Pb2+. The colorless solution of REHBA changes to pink for Cu2+/Co2+ and shows a remarkable fluorescence for Pb2+. The further differentiation of Cu2+ and Co2+ depends on whether the colorimetric response of REHBA is reversible upon addition of ethylene diamine tetraacetic acid. The response is reversible for Cu2+, while it is not for Co2+. The spirolactam ring-opening in REHBA and the formation of REHBA-metal complexes with binding stoichiometric ratio of 1:1 are responsible for the UV-visible and fluorescence behaviors. REHBA shows excellent selectivity, anti-interference and good sensitivity. The limit of detection of Cu2+, Co2+ and Pb2+ is 0.11 µM, 0.88 µM and 0.73 µM, respectively. In addition, REHBA has been applied to recognize Pb2+ in living cells by fluorescence image and Cu2+, Co2+ and Pb2+ in real water samples, indicating that REHBA is a potential candidate for multi-metal-ions detection.

A novel multi-purpose Zn-MOF fluorescent sensor for 2,4-dinitrophenylhydrazine, picric acid, La3+ and Ca2+: Synthesis, structure, selectivity, sensitivity and recyclability.

A new three-dimensional luminescence Zn-MOF sensor with the molecular formula [Zn4(µ3-OH)2(ptptc)1.5(DMA)(H2O)2]·2DMA (complex 1) for the selective sensing of 2,4-dinitrophenylhydrazine (2,4-DNPH), picric acid (PA), La3+ and Ca2+ has been synthesized from terphenyl-3,3',5,5'-tetracarboxylic acid (H4ptptc) and zinc nitrate under solvothermal conditions. XRD analysis reveals that complex 1 crystallizes in monoclinic system P21/n space group and consists of a three-dimensional network with one-dimensional channels, which are expected to facilitate the diffusion, concentration and detection processes. Real-time fluorescence quenching responses and good reversibility were observed in the fluorescence titration experiments with nano-molar scale detection limits for 2,4-dinitrophenylhydrazine (2,4-DNPH, 100 nM) and picric acid (PA, 500 nM). Noticeable emission band shift from 365 nm to 420 nm was observed when treated complex 1 with La3+ and a new emission band centered at 475 nm appeared when treated complex 1 with Ca2+ in the metal ions sensing experiments. In virtue of its high selectively, good sensitively and recyclability complex 1 could be a promising fluorescent sensor for explosives and metal ions.