Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

Design, synthesis, and biological evaluation of novel donepezil-tacrine hybrids as multi-functional agents with low neurotoxicity against Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and deficits in cognitive domains. Low choline levels, oxidative stress, and neuroinflammation are the primary mechanisms implicated in AD progression. Simultaneous inhibition of acetylcholinesterase (AChE) and reactive oxygen species (ROS) production by a single molecule may provide a new breath of hope for AD treatment. Here, we describe donepezil-tacrine hybrids as inhibitors of AChE and ROS. Four series of derivatives with a ß-amino alcohol linker were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit AChE and butyrylcholinesterase (BuChE) in vitro, using tacrine (hAChE, IC50 = 305.78 nM; hBuChE, IC50 = 56.72 nM) and donepezil (hAChE, IC50 = 89.32 nM; hBuChE, IC50 = 9137.16 nM) as positive controls. Compound B19 exhibited an excellent and balanced inhibitory potency against AChE (IC50 = 30.68 nM) and BuChE (IC50 = 124.57 nM). The cytotoxicity assays demonstrated that the PC12 cell viability rates of compound B19 (84.37 %) were close to that of tacrine (87.73 %) and donepezil (79.71 %). Potential therapeutic effects in AD were evaluated using the neuroprotective effect of compounds against H2O2-induced toxicity, and compound B19 (68.77 %) exhibited substantially neuroprotective activity at the concentration of 25 µM, compared with the model group (30.34 %). Furthermore, compound B19 protected PC12 cells from H2O2-induced apoptosis and ROS production. These properties of compound B19 suggested that it was a multi-functional agent with AChE inhibition, anti-oxidative, anti-inflammatory activities, and low toxicity and that it deserves further investigation as a promising agent for AD treatment.

Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease.

In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC50 = 30.35 ± 2.07 nM) and human butyrylcholinesterase (hBuChE, IC50 = 48.03 ± 6.41 nM) with minimal neurotoxicity. Further investigations have demonstrated that C7 exhibited a remarkable capacity to safeguard PC12 cells against H2O2-induced apoptosis and effectively suppressed the production of reactive oxygen species (ROS). Moreover, in an inflammation model of BV2 cells induced by lipopolysaccharide (LPS), C7 effectively attenuated the levels of pro-inflammatory cytokines. After 12 h of dialysis, C7 continued to exhibit an inhibitory effect on cholinesterase activity. An acute toxicity test in vivo demonstrated that C7 exhibited a superior safety profile and no hepatotoxicity compared to the parent nucleus tacrine. In the scopolamine-induced AD mouse model, C7 (20 mg/kg) significantly reduced cholinesterase activity in the brain of the mice. C7 was tested in a pharmacological AD mouse model induced by Aß1-42 and attenuated memory deficits at doses as low as 5 mg/kg. The pseudo-irreversible cholinesterase inhibitory properties and multifunctional therapeutic attributes of C7 render it a promising candidate for further investigation in the treatment of AD.

Decomposition and decoupling analysis of multi-sector CO2 emissions based on LMDI and Tapio models: Case study of Henan Province, China.

The peak carbon dioxide emissions at the provincial level is the foundation for achieving the national target of carbon emission peak, thus it is important to analyze the characteristics of provincial CO2 emissions. However, there is a lack of comprehensive analysis and research on quantifying the contributions of the driving factors to decoupling at the provincial level. Therefore, taking Henan Province as the research object, this study establishes the decoupling effort model by combining the traditional LMDI model and Tapio model based on compiling the CO2 emission inventories from 2006 to 2019. The results showed that total CO2 emissions increased from 2006 to 2011, and decreased after 2011 in Henan Province. Raw coal was the primary fuel source of Henan's CO2 emissions, and the sector of "power and heat production" was the major industrial source, accounting for above 45% of the total emissions. Economic output and energy intensity were the major factors promoting and restraining the increase in Henan's CO2 emissions, respectively. In terms of the decoupling state, Henan achieved the transformation from weak decoupling to strong decoupling from 2006 to 2019. Industry presented a strong decoupling condition, while weak decoupling was detected in the agriculture sector during the study period. The changing trend of energy intensity decoupling effort was consistent with that of total decoupling effort, indicating that energy intensity is a crucial factor in achieving decoupling. This study is helpful to grasp the CO2 emission characteristics of Henan Province and provide the theoretical basis for formulating emission mitigation measures of peak carbon dioxide emissions in Henan and other provinces.

Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease.

Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca2+ homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca2+ release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC50 = 0.162 µM) and AChE (inhibition (%) = 93.5, IC50 = 0.372 µM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD.

Progress in partially degradable titanium-magnesium composites used as biomedical implants.

Titanium-magnesium composites have gained increasing attention as a partially degradable biomaterial recently. The titanium-magnesium composite combines the bioactivity of magnesium and the good mechanical properties of titanium. Here, we discuss the limitations of conventional mechanically alloyed titanium-magnesium alloys for bioimplants, in addition we summarize three suitable methods for the preparation of titanium-magnesium composites for bioimplants by melt: infiltration casting, powder metallurgy and hot rotary swaging, with a description of the advantages and disadvantages of all three methods. The titanium-magnesium composites were comprehensively evaluated in terms of mechanical properties and degradation behavior. The feasibility of titanium-magnesium composites as bio-implants was reviewed. In addition, the possible future development of titanium-magnesium composites was discussed. Thus, this review aims to build a conceptual and practical toolkit for the design of titanium-magnesium composites capable of local biodegradation.

Preparation of CaF2 Microspheres with Nanopetals for Water Vapor Adsorption.

The hierarchically structured flower-like CaF2 microspheres with nanopetals, named FL-CaF2, were synthesized via a hydrothermal method using calcium acetate Ca(Ac)2 and NaBF4 as calcium and fluorine sources, respectively, assisted by the chelating reagent trisodium citrate (Na3Cit) with the optimal pH of the synthesis solution. Meanwhile, a reference sample, named FL-CaF2-R, was reproduced using ethylenediaminetetraacetic acid disodium salt (Na2EDTA) as the chelating reagent, based on the recipe and synthesis procedure from the literature. Various techniques such as X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform-infrared spectroscopy, and N2 adsorption-desorption at 77 K were then used to characterize the synthesized samples. The results show that FL-CaF2 with a larger diameter has a much higher thermal stability than FL-CaF2-R because the larger the nanocrystallite size, the higher the thermal stability. The adsorption of water vapor on CaF2 is irreversible because CaF2 can interact with the adsorbed water molecules strongly. The dual-site Langmuir model was used to describe the measured adsorption isotherms of water vapor on FL-CaF2 at low water vapor pressures and 298, 308, and 318 K. FL-CaF2 has a much higher water-adsorption capacity than those reported in the literature. Furthermore, the isosteric heat of adsorption as a function of loading, derived from the measured isotherms, varies from ca. 46 to 43 kJ mol-1 in the whole loading range investigated. Finally, the applications of FL-CaF2 are anticipated in the dehydration of hydrogen fluoride gas as well as in catalysis.

An eco-friendly fluorometric polymer nanoparticle for selectively monitoring sulfadiazine in tap water.

An eco-friendly fluorescence polymer nanoparticle based on carbon quantum dots and poly(methyl methacrylate) nanoparticles is successfully fabricated to detect sulfadiazine. By making use of the abundant functional group of carbon quantum dots and poly(methyl methacrylate) nanoparticles, without any extra modification, the synthetic process of the fluorescence nanoparticles is reduced and the unnecessary chemical molecules are avoided being brought into the reaction system. The investigation of the fluorescence property of carbon quantum dots shows that the prepared carbon quantum dots are the excitation independent. In addition, the morphology of the synthesized fluorescence polymer nanoparticle is tested by the scanning electron microscope and shows that the fluorescence sensor possesses a good spherical core-shell structure. Moreover, under the optimized condition, the prepared fluorescence polymer nanoparticle possesses a good selectivity in the detection of sulfadiazine under a mixture solution. Moreover, the limit of detection is 4 µmol.l-1 within the detective range from 10 µmol.l-1 to 60 µmol.l-1. Meanwhile, the fluorescence quenching mechanism is considered with the photoinduced electron transfer mechanism. Finally, the practical research on the detection of sulfadiazine in tap water shows that the recovery range and relative standard deviation are 97.5% - 105.1% and 2.1%-4.5%, respectively.

A sensitive electrochemical sensor modified with multi-walled carbon nanotubes doped molecularly imprinted silica nanospheres for detecting chlorpyrifos.

A highly sensitive and convenient electrochemical sensor, based on surface molecularly imprinted polymers and multiwalled carbon nanotubes, was successfully developed to detect chlorpyrifos in real samples. In order to solve the problems like uneven shapes, poor size accessibility, and low imprinting capacity, the layer of the molecularly imprinted polymer was prepared on the surface of silica nanospheres. Moreover, the doping of multiwalled carbon nanotubes greatly improved the electrical properties of developed sensor. Under the optimal conductions, the electrochemical response of the sensor is linearly proportional to the concentration of chlorpyrifos in the range of 5.0 × 10-12 -5.0 × 10-8  mol/L with a low detection limit of 8.1 × 10-13  mol/L. The prepared sensor exhibited multiple advantages such as low cost, simple preparation, convenient use, excellent selectivity, and good reproducibility. Finally, the prepared sensor was successfully used to detect chlorpyrifos in vegetable and fruit.

Ratiometric fluorescence nanosensors based on core-shell structured carbon/CdTe quantum dots and surface molecularly imprinted polymers for the detection of sulfadiazine.

Sulfadiazine is an environmental pollutant derived from abuse of antibiotics. Its content in environmental water is closely related to human health. Thus, a novel dual-emission surface molecularly imprinted nanosensor is designed for the specific adsorption and detection of sulfadiazine. In the system, blue emissive carbon quantum dots wrapped with silica served as the internal reference signal for eliminating background interference, while red emissive thioglycolic acid modified CdTe quantum dots (CdTe QDs), which are low dimensional semiconductor materials by the combination of cadmium and tellurium with excellent optical properties, were encapsulated in the imprinted layer to offer recognition signal. The fluorescence of CdTe quantum dots was quenched and the fluorescence quenching degree of carbon quantum dots was inconspicuous with the increase of concentration of sulfadiazine, thereby reflecting the color change. The detection of sulfadiazine was successfully achieved in a concentration range of 0.25-20 µmol/L with detection limit of 0.042 µmol/L and nanosensors had specific recognition for sulfadiazine over its analogues. Compared to single-emission fluorescence sensors, ratiometric fluorescence nanosensors had wider linear range and higher detection accuracy. Furthermore, the nanosensors were also successfully applied for the determination of sulfadiazine in real water and milk samples with acceptable recoveries. The study provides a feasible method for the detection of sulfadiazine and a reference for the detection of sulfonamides.

Novel Thermosensitive Core⁻Shell Surface Molecularly Imprinted Polymers Based on SiO2 for the Selective Adsorption of Sulfamethazine.

In this research, a novel, sulfamethazine, thermosensitive, molecularly-imprinted polymer (MIP) with an obvious core⁻shell structure for the enrichment of sulfamethazine (SMZ), which involved temperature sensitive monomer N-Isopropylacrylamide, functional monomer methacrylic acid and cross-linking agents ethyleneglycol dimethacrylate (EGDMA) and N,N'-methylenebisacrylamide, was successfully compounded using the surface polymerization method. To ensure the best experimental group, we designed and compared three groups of controlled experiments of MIPs with different crosslinking agents. When the adsorption temperature was almost the lower critical solution temperature (LCST) of Poly(N-Isopropylacrylamide), the preparative MIPs showed outstanding adsorption capacity and specific identification to sulfamethazine. Moreover, this allowed the MIPs to better facilitate by combining the template molecules, as well as optimizing the imprinting factor. In addition, after 80 min, the adsorption of the MIPs leveled off and remained constant, and the adsorption quantity reached (a maximum of) at 8.1 mg·g-1.