Construction of a super large Stokes shift near-infrared fluorescent probe for detection and imaging of superoxide anion in living cells, zebrafish and mice.

As one of the major reactive oxygen species (ROS), superoxide anion (O2•-) is engaged in maintaining redox homeostasis in the cell microenvironment. To identify the pathological roles in related disorders caused by abnormal expression of O2•-, it is of great significance to monitor and track the fluctuation of O2•- concentration in vivo. However, the low concentration of O2•- and the interference caused by tissue autofluorescence make the development of an ideal detection methodology full of challenges. Herein, a "Turn-On" chemical response near-infrared (NIR) fluorescence probe Dcm-Cu-OTf for O2•- detection in inflamed models, was constructed by conjugating the NIR fluorophore (dicyanisophorone derivative) with an O2•- sensing moiety (trifluoromethanesulfonate). Dcm-Cu-OTf exerted about 140-fold fluorescence enhancement after reacting 200 µM O2•- with an excellent limited of detection (LOD) as low as 149 nM. Additionally, Dcm-Cu-OTf exhibited a super large Stokes shift (260 nm) and high selectivity over other bio-analytes in stimulated conditions. Importantly, Dcm-Cu-OTf showed low toxicity and enabled imaging of the generation of O2•- in the Lipopolysaccharide (LPS)-stimulated HeLa cells, zebrafish, and LPS-induced inflamed mice. The present study provided a potential and reliable detection tool to inspect the physiological and pathological progress of O2•- in living biosystems.

Reactive Chlorine Species Advancing the Atmospheric Oxidation Capacities of Inland Urban Environments.

Chlorine (Cl) radicals from photolabile chlorine species are highly reactive and can affect the fate of air pollutants in the atmosphere. Although several campaigns have been conducted, typically in coastal environments, long-term observations of reactive chlorine species and their impacts on atmospheric oxidation capacities (AOCs) are lacking. Here, we report nearly full-year observations of Cl2 and ClNO2 levels in Beijing and evaluate their impacts on the AOC with a box model coupled with Cl chemistry. Cl radicals promote the circulation of OH-HO2-RO2 by accelerating the OH chain lengths by up to 12.6% on average, hence boosting the AOC, especially in the winter or spring. This promotion effect is nonlinearly dependent on the VOC and NOx concentrations, thus leading to a slight shift in ozone formation from a VOC-sensitive regime to a transition regime with seasonal differences. Given the ubiquitous reactive chlorines in polluted inland urban regions, the AOCs and the formation of secondary pollutants will be underestimated if the reactive chlorine species are neglected.

Catalytic Oxidation Mechanism of Toluene over CexMn1-xO2: The Role of Oxygen Vacancies in Adsorption and Activation of Toluene.

Catalytic oxidation has been extensively studied as a promising technology for the removal of toluene from industrial waste gases and indoor air. However, the debate regarding the oxidation mechanism is far from resolved. CexMn1-xO2 catalysts with different mixing ratios are prepared by the sol-gel method and found to exhibit better catalytic activities for toluene oxidation than a single oxide. Characterizations and theoretical calculations reveal that the doped Mn increases the number of oxygen vacancies and the ability of oxygen vacancies to activate aromatic rings, which promotes the rate-determining step of toluene oxidation, i.e., ring-opening reactions. The oxidation products detected by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and Vocus proton transfer reaction mass spectrometry (Vocus-PTR-MS) show that the doped Mn significantly improves the ring-opening efficiency and subsequently yields more short-chain products, such as pyruvic acid and acetic acid. A comprehensive oxidation pathway of toluene is refined in this work.

Binaphthyl-Based Chiral Macrocyclic Hosts for the Selective Recognition of Iodide Anions.

In this study, we explorethe synthesis of binaphthyl-based chiral macrocyclic hosts for the first time. They exhibited the selective recognition abilities of iodide anions which can be favored over those of other anions (AcO-, NO3-, ClO4-, HSO4-, Br-, PF6-, H2PO4-, BF4-, and CO3F3S-), as confirmed by UV-vis, HRMS, and 1H NMR spectroscopy experiments, as well as DFT calculations. Neutral aryl C-H···anion interactions play an important role in the formation complexes. The recognition process can be observed by the naked eye.

The contribution of industrial emissions to ozone pollution: identified using ozone formation path tracing approach.

Wintertime meteorological conditions are usually unfavorable for ozone (O3) formation due to weak solar irradiation and low temperature. Here, we observed a prominent wintertime O3 pollution event in Shijiazhuang (SJZ) during the Chinese New Year (CNY) in 2021. Meteorological results found that the sudden change in the air pressure field, leading to the wind changing from northwest before CNY to southwest during CNY, promotes the accumulation of air pollutants from southwest neighbor areas of SJZ and greatly inhibits the diffusion and dilution of local pollutants. The photochemical regime of O3 formation is limited by volatile organic compounds (VOCs), suggesting that VOCs play an important role in O3 formation. With the developed O3 formation path tracing (OFPT) approach for O3 source apportionment, it has been found that highly reactive species, such as ethene, propene, toluene, and xylene, are key contributors to O3 production, resulting in the mean O3 production rate (PO3) during CNY being 3.7 times higher than that before and after CNY. Industrial combustion has been identified as the largest source of the PO3 (2.6 ± 2.2 ppbv h-1), with the biggest increment (4.8 times) during CNY compared to the periods before and after CNY. Strict control measures in the industry should be implemented for O3 pollution control in SJZ. Our results also demonstrate that the OFPT approach, which accounts for the dynamic variations of atmospheric composition and meteorological conditions, is effective for O3 source apportionment and can also well capture the O3 production capacity of different sources compared with the maximum incremental reactivity (MIR) method.

A Benzothiadiazole-Based Self-Assembled Cage for Cadmium Detection.

A turn-on fluorescent probe, cage 1, was efficiently self-assembled by condensing 4,4'-(benzothiadiazole-4,7-diyl)dibenzaldehyde and TREN in chloroform. The formation of cage 1 was characterized and confirmed by NMR spectroscopy, mass spectrometry, and theoretical calculations. The yield of cage 1 could be controlled by tuning the reaction conditions, such as the precursor concentration. Interestingly, the addition of 10 equiv of Cd2+ relative to cage 1 could increase the fluorescence almost seven-fold. 1H NMR and fluorescence experiments indicating fluorescence enhancement may be caused by the decomposition of cage 1. Such a high selectivity toward Cd2+ implies that the cage could potentially be employed in cadmium detection.

A highly selective and easily acquisitive near-infrared fluorescent probe for detection and imaging of hydrogen sulfide in cells.

Hydrogen sulfide (H2S) plays a substantial role as a messenger in the physiological and pathological processes of many diseases. Recently, the fluorescence probe of H2S based on organic dye has attracted great attention. However, the emission of many probes is in the UV-vis region (400-600 nm), so it has the disadvantages of shallow tissue penetration and more vulnerable to spontaneous fluorescence interference. Although several H2S probes have been developed that emit more than 650 nm, there is a complex structure difficult to synthesize or unstable in storage. Aimed at simply structural and easily synthesized H2S fluorescent probes with emission wavelength more than 650 nm, a novel near-infrared (NIR) probe (NIR-H2S) here was rationally designed with 4-(2-carboxyphenyl)-7-(diethylamino)-2-(4-hydroxystyryl)chromenylium (NIR-OH) as a fluorescent dye and 2,4-dinitrophenyl moiety as a recognition group. Addition of H2S, the "turn-on" NIR fluorescence response at 736 nm of NIR-H2S was displayed, accompanied by a visual colour change from purple to green when excited at 686 nm. As an easily acquisitive H2S probe, NIR-H2S has been successfully applied to cell imaging for H2S detection with the advantages such as long fluorescence emission, low toxicity, high sensitivity and strong selectivity.

Two phenanthroimidazole turn-on probes for the rapid detection of selenocysteine and its application in living cells imaging.

Detection of selenocysteine (Sec) content in cells by fluorescence probe is of great significance for the identification of human related diseases. To achieve fast and sensitive detection of Sec, two isomers A4 and B4 as turn-on fluorescent probes to detect Sec were designed and synthesized. Both A4 and B4 display fast turn-on response, high selectivity and sensitivity toward Sec, which can be applied for fluorescence imaging of Sec in living cells. Compared with B4, A4 has a larger Stokes shift (125 nm), wider pH range (5-10) and lower detection limit (65.4 nM) due to its ESIPT (excited state intramolecular proton transfer) effect. In view of the detection performance of these two probes, they can be used as effective tools for detecting Sec in biological systems.

Medicinal chemistry updates of novel HDACs inhibitors (2020 to present).

Epigentic enzymes histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-N-acetylated lysine residues of various protein substrates including both histone and non-histone proteins. Different HDACs have distinct biological functions and are recruited to specific regions of the genome. Due to their important biological functions, HDACs have been validated in clinics for anticancer therapy, and are being explored for potential treatment of several other diseases such as Alzheimer disease (AD), metabolic disease, viral infection, and multiple sclerosis, etc. Besides five approved drugs, there are more than thirty HDACs inhibitors currently being investigated in clinical trials. Centering on the advances of drug discovery programs in this field since 2020, this review discusses HDACs inhibitors from the aspects of the structure-based rational design, isoform selectivity, pharmacology, and toxicology of the compounds of interest. The hope is to provide the medicinal chemistry community with up-to-date information and to accelerate the drug discovery programs in this area.

Genomic insights into Pseudoalteromonas sp. JSTW coping with petroleum-heavy metals combined pollution.

Worldwide marine compound contamination by petroleum products and heavy metals is a burgeoning environmental concern. Pseudoalteromonas, prevalently distributed in marine environment, has been proven to degrade petroleum and plays an essential role in the fate of oil pollution under the combined pollution. Nevertheless, the research on the reference genes is still incomplete. Therefore, this study aims to thoroughly investigate the reference genes represented by Pseudoalteromonas sp. JSTW via whole-genome sequencing. Next-generation sequencing technology unfolded a genome of 4,026,258 bp, database including Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to annotate the genes and metabolic pathways conferring to petroleum hydrocarbon degradation. The results show that common alkane and aromatic hydrocarbon degradation genes (alkB, ligB, yqhD, and ladA), chemotaxis gene (MCP, cheA, cheB, pcaY, and pcaR), heavy-metal resistance, and biofilm genes (σ54, merC, pcoA, copB, etc.) were observed in whole-genome sequence (WGS) of JSTW, which indicated that strain JSTW could potentially cope with combined pollution. The degradation efficiency of naphthalene in 60 h by JSTW was 99% without Cu2+ and 67% with 400 mg L-1 Cu2+ . Comparative genome analysis revealed that genomes of Pseudoalteromonas lipolytica strain LEMB 39 and Pseudoalteromonas donghaensis strain HJ51 shared similarity with strain JSTW, suggesting they are also the potential degradater of petroleum hydrocarbons under combined pollution. Therefore, this study provides a WGS annotation and reveals the mechanism of response to combined pollution of Pseudoalteromonas sp. JSTW.

Macrocyclic Photoinitiator Based on Prism[5]arene Matching LEDs Light with Low Migration.

In this work, a naphthalene-based macrocycle prism[5]arene (NP5 OCH3 ) is developed as a novel kind of photoinitiator. When NP5 OCH3 is irradiated under light, the bond between methylene and naphthalene can be quickly broken owning to the existence of ring tension. The macrocycle is cleaved to linear oligomer biradicals, which can effectively initiate the free radical photopolymerization of acrylate monomers. Compared with conventional photoinitiators, NP5 OCH3 has strong light absorption in the wavelength range of 365-405 nm, so it can well match the environment-friendly light-emitting diodes (LEDs) light source to realize highly efficient initiation. In addition, there is no small molecule fragment generated during NP5 OCH3 fracture, and the resulted linear oligomer biradicals can be immobilized in the polymer after initiating polymerization, so NP5 OCH3 photoinitiators show much lower migration rate and cytotoxicity. Cleavable macrocycle prismarene may provide a new idea for the design of safe and efficient photoinitiators matching long wavelength light.

A FRET-ICT Dual-Modulated Ratiometric Fluorescence Sensor for Monitoring and Bio-Imaging of Cellular Selenocysteine.

Since the fluctuation of cellular selenocysteine (Sec) concentration plays an all-important role in the development of numerous human disorders, the real-time fluorescence detection of Sec in living systems has attracted plenty of interest during the past decade. In order to obtain a faster and more sensitive small organic molecule fluorescence sensor for the Sec detection, a new ratiometric fluorescence sensor Q7 was designed based on the fluorescence resonance energy transfer (FRET) strategy with coumarin fluorophore as energy donor and 4-hydroxy naphthalimide fluorophore (with 2,4-dinitrobenzene sulfonate as fluorescence signal quencher and Sec-selective recognition site) as an energy acceptor. The sensor Q7 exhibited only a blue fluorescence signal, and displayed two well distinguished emission bands (blue and green) in the presence of Sec with ∆λ of 68 nm. Moreover, concentrations ranging of quantitative detection of Sec of Q7 was from 0 to 45 µM (limit of detection = 6.9 nM), with rapid ratiometric response, high sensitivity and selectivity capability. Impressively, the results of the living cell imaging test demonstrated Q7 has the potentiality of being an ideal sensor for real-time Sec detection in biosystems.

A Red Emissive Fluorescent Turn-on Sensor for the Rapid Detection of Selenocysteine and Its Application in Living Cells Imaging.

The content of selenocysteine in cells has an important effect on a variety of human diseases, and the detection of selenocysteine by fluorescent sensors in vivo has shown many advantages. In order to further develop fast-reaction-time, good-selectivity, and high-sensitivity long-wavelength selenocysteine fluorescent sensors, we designed and synthesized the compound YZ-A4 as a turn-on fluorescent sensor to detect the content of selenocysteine. The quantitative detection range of the sensor YZ-A4 to selenocysteine was from 0 to 32 µM, and the detection limit was as low as 11.2 nM. The sensor displayed a rapid turn-on response, good selectivity, and high sensitivity to selenocysteine. Finally, we have demonstrated that YZ-A4 could be used for fluorescence imaging of selenocysteine in living cells.

Current advances on waste biomass transformation into value-added products.

Ceaseless growth in human population led to high demand in everything. Currently, the world largely depends on petroleum-based "all material synthesis" scheme. On the other hand, depletion of fossil-based resources and their huge impact on environmental pollution have forced us to search for sustainable and eco-friendly alternative resources. In this context, the notion to utilize waste biomass could possibly provide environmental and economic benefits. This study was carefully designed to critically review state of the art in the transformation of waste biomass into value-added products. Even though extensive reviews on biomass utilization have been published in the past few years, the current study basically focused on new trends and prospective in this area. Here, global biomass potential, research developments and practices, novel biomass transformation approaches, and future perspectives were broadly discussed. More importantly, in addition to revising published researches, already implemented and ongoing large-scale projects on valorization of waste biomass have been assessed. Therefore, this study is believed to give crucial information on the current status and future direction of waste biomass utilization so as to accomplish the quest towards green economy.Key Points • Huge biomass potential and dramatically increase in R&D trends on waste biomass.• Selection of appropriate waste biomass valorization techniques. • Development of efficient and feasible waste biomass transformation technology. • Coproduction of low-value, high-volume and high-value, low volume products.

Butyrylcholinesterase K variant and Alzheimer's disease risk: a meta-analysis.

BACKGROUND: Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. MATERIAL/METHODS: We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE ε4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE ε4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). CONCLUSIONS: The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk.

Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.

BACKGROUND: In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramat's bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures. RESULTS: All of the analogues have been identified on the basis of (1)H NMR, ESI-MS and elemental analysis data. The activities of these analogues were evaluated against three organisms, and biological assays indicated that compounds 5f, 5h and 5u possessed better insecticidal activities against bean aphids (Aphis fabae) than the lead compound spirotetramat. The LC50 of 5f, 5h and 5u against bean aphids reached 0.42, 0.28 and 2.53 mg L(-1) respectively. Moreover, some compounds possessed comparable activities against carmine spider mite (Tetranychus cinnabarinus) and oriental armyworm (Mythimna sepatara) with spirotetramat. The structure-activity relationships (SARs) indicated that the flexible bridge at position C-4 of spirotetramat was important for its bioactivities, and the size of the group at position C-8 would have great influence on the activities. Furthermore, the log P values lower than 6.0 may be favourable for insecticidal activities. CONCLUSION: The present work demonstrates that some spirotetramat analogues can be used as potential lead compounds for developing novel insecticides, and preliminary SAR analysis would provide information for the utilisation of spirotetramat analogues as potential lipid biosynthesis inhibitors.

Design, synthesis, and analysis of the quantitative structure-activity relationships of 4-phenyl-acyl-substituted 3-(2,5-dimethylphenyl)-4-hydroxy-1-azaspiro[4.5]dec-3-ene-2,8-dione derivatives.

A series of 4-phenyl-acyl-substituted 3-(2,5-dimethylphenyl)-4-hydroxy-1-azaspiro[4.5]dec-3-ene-2,8-dione derivatives were designed and synthesized, and their structures were characterized using (1)H NMR (or (13)C NMR), mass spectrometry, and elemental analysis. The bioactivities of the new compounds were evaluated. These compounds exhibited good inhibition activities against bean aphids (Aphis fabae) and carmine spider mite (Tetranychus cinnabarinus), and 4-phenyl acyl esters showed stronger bioactivity than 4-arylesterases and alkyl esters. The results showed that compound 8-I-e, which contains a para-methoxy group on the phenyl acyl, and compound 8-I-m, which contains a para-trifluoromethyl group on the phenyl acyl, displayed potent insecticidal activity against A. fabae and T. cinnabarinus respectively. The insecticidal activity showed a clear structure-activity relationship, confirming the importance of the flexible bridge. The DFT/B3LYP/6-31(d) level method was used to calculate molecular geometries and electronic descriptors. These factors included total energy, charge distribution, and the linear orbital level of the title compounds. Quantitative structure-activity relationship studies were performed on these compounds using quantum-chemical and physicochemical parameters as independent variables and insecticidal activity as a dependent variable. Insecticidal activity was most closely correlated (r > 0.8) with quantum chemical and physicochemical parameters.

Synthesis and bioactivity evaluation of novel spiromesifen derivatives.

BACKGROUND: The development of environmentally friendly and novel structural pesticides is now an area of intense research in the agriculture field. Spirocyclic tetronic acids such as spiromesifen are typical compounds of this kind. In order to discover novel compounds with improved and broader-spectrum insecticidal activities, a series of spiromesifen derivatives were synthesised and bioassayed. RESULTS: The derivatives were identified by (1) H NMR and MS. Preliminary bioassays demonstrated that some bioactivities of compounds 5a to 5u were better and had a broader spectrum than the lead compound spiromesifen. Moreover, these compounds showed better insecticidal activities against Mythimna sepatara and Aphis fabae than acaricidal activities against Tetranychus cinnabari. Furthermore, LC(50) of 5s against Aphis fabae reached 1.09 mg L(-1) . At the same time, compounds 5g, 5i, 5k and 5r also warrant further study because of their superior bioactivities to spiromesifen. What is more, suitable carbon chain length in the 4-position ester and the log P value of these spiromesifen derivatives dramatically influenced their insecticidal activities. Butyric or pentanoic ester and a log P value of 4.0-6.0 may be preferred. CONCLUSION: The present work demonstrates that some spiromesifen derivatives can be used as potential lead compounds for developing novel insecticides and acaricides.

3-tert-Butyl-2-oxo-1-oxaspiro-[4.5]dec-3-en-4-yl 4-chloro-benzoate.

The title tetronic acid derivative, C(20)H(23)ClO(4), which is a spiro-diclofen analogue, has two crystallographically independent mol-ecules in the asymmetric unit (Z' = 2). The cyclo-hexane rings in the respective mol-ecules A and B adopt chair conformations [four C atoms are planar with mean deviations of 0.013 (2) and 0.001 (2) Å, and the flap positions deviate by 0.653 (4) and -0.663 (3) Š(mol-ecule A) and 0.642 (4) and -0.643 (5) Š(mol-ecule B) from the plane]. The furan ring makes dihedral angles of 86.9 (1) (mol-ecule A) and 85.4 (1)° (mol-ecule B) with the respective benzene rings.

[Application of neuroendoscope in the treatment of skull base chordoma].

OBJECTIVE: To further explore the application, approach, indication and prognosis of neuroendoscope treatment for skull base chordoma. METHODS: A total of 101 patients of skull base chordoma were admitted at our hospital from May 2000 to April 2010. There were 59 males and 42 females. Their major clinical manifestations included headache, cranial nerve damage and dyspnea. They were classified according to the patterns of tumor growth: Type I (n = 13): tumor location at a single component of skull base, i. e. clivus or sphenoid sinus with intact cranial dura; Type II (n = 56): tumor involving more than two components of skull e. g clivus, sphenoid and nasal/oral cavity, etc. But there was no intracranial invasion; Type III (n = 32) : tumor extending widely and intradurally forming compression of brain stems and multiple cranial nerves. Based on the types of chordoma, different endoscopic approaches were employed, viz. transnasal, transoral, trans-subtemporal fossa and plus microsurgical craniotomy for staging in some complex cases. RESULTS: Among all patients, total resection was achieved (n = 19), subtotal (n = 58) and partial (n = 24). In partial resection cases, 16 cases were considered to be subtotal due to a second-stage operation. Most cases had conspicuous clinical improvements. Self-care recovery within one week post-operation accounted for 58.4%, two weeks 30.7%, one month 6.9% and more than one month 1.9%. Postoperative complications occurred in 13 cases (12.8%) and included CSF leakage (n = 4) cranial nerve palsy (n = 5), hemorrhagic nasal wounds (n = 3) and delayed intracranial hemorrhage (n = 1). All of these were cured or improved after an appropriate treatment. A follow-up of 6 - 60 months was conducted in 56 cases. CONCLUSION: Early detection and early treatment are crucial for achieving a better outcome in chordoma. Neuroendoscopic treatment plays an important role in managing those complicated cases. Precise endoscopic techniques plus different surgical approaches and staging procedures are required to improve the post-operative quality of life for patients.