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A new type of xanthene-based fluorescent probe capable of intracellular subtle pH fluctuation sensing was developed. The probe underwent reversible deprotonation-protontation processes and therefore generated two states with distinct contrast in fluorescence emission features. In the physiological range (pH 7.0–8.0), the probe markedly presented 31.2% fluorescence signal change upon pH fluctuation of 0.1 pH unit, enabling sensitivity infinitely superior to previous fluorescent pH probes. The preliminary biological experiments revealed the large dynamic range of the probe for intracellular pH sensing within the range of pH 6.0–8.0. Owing to its sensitive responses to pH fluctuation in the physiological pH range, the probe definitely demonstrated its ability for “distinguishing” tumor from normal cells based on the difference in microenvironment pH level between the former and the latter. The figure of merits of the probe, including pKa (7.45) in the physiological pH range, excellent photostability, extraordinary large dynamic range for pH sensing, as well as the preliminary bioimaging results regarding differentiating tumor from normal cells are indicative of its potential for providing the microenvironment information regarding the interfacial features at the perimeter of tumor tissues by presenting high-contrast fluorescence images.

A new type of colorimetric, fluorescent palladium (Pd) probe characterized with beaconing fluorescence signal in the quiet near-infrared (NIR) region (centered ~ 717 nm), recognition response time of approximately 3 min, limit of detection (LOD) down to 5.1 ppb, and excellent recognition specificity over a wide range of interfering metal cations was developed. It is believed that the probe underwent sequential Pd0-mediated oxidative addition and reduction elimination reactions, yielding typical D-π-A molecular skeleton of the final reaction product capable of intramolecular charge transfer (ICT). The benzothiazole moiety of the probe molecular skeleton is believed to play a vital trole in shifting the beaconing fluorescence signal to the quiet NIR region and accelerating the Pd0 recognition process of the probe via the formation of the fluorescent reaction product with largely extended π-delocalization. With unique advantages, the fluorescent probe we developed will find practical applications for detecting residual Pd with concentration below the safety margin in pharmacy and biomedical engineering.

A new type of fluorescent probe capable of detecting a sulfur mustard (SM) simultant at a concentration of 1.2 μM in solution and 0.5 ppm in the gas phase has been developed. Owing to its molecular structure with a thiocarbonyl component and two piperidyl moieties integrated into the xanthene molecular skeleton, this probe underwent a highly selective nucleophilic reaction with the SM simultant and generated a thiopyronin derivative emitting intensive pink fluorescence. The distinct difference in electronic structure between the probe and thiopyronin derivative generated a marked shift of the absorption band from 445 to 567 nm, which enabled an optimal wavelength propitious for exciting the thiopyronin derivative but adverse to the probe. Such efficient separation of the excitation wavelength and tremendous increase in fluorescence quantum yield, from less than 0.002 to 0.53, upon conversion from the probe to the thiopyronin derivative, jointly led to a distinct contrast in the beaconing fluorescence signal (up to 850-fold) and therefore the unprecedented sensitivity for detecting SM species.

Biomimetic fluorescent nanoprobes capable of emitting near-infrared (NIR) fluorescence (λmax ≈ 720 nm) upon excitation of 800 nm light were developed. The key conjugated polymer enabled two-photon absorption and Forster resonance energy transfer (FRET) processes within the nanoprobes, which imparted the nanoprobes with ideal NIR-incoming-NIR-outgoing fluorescence features. The cancer cell membrane (CM) coating endowed these nanoprobes with perfect biocompatibility and highly specific targeting ability to homologous tumors. It was believed that CM encapsulation provided an additional protecting layer for the photoactive components residing in the core of nanoprobes for retaining their intrinsic fluorescing ability in the physiological milieu. The long-term structural integrity, excellent photostability (fluorescence decrease

On the basis of the unique physicochemical properties of graphene quantum dots (GQDs), we developed a novel type of theranostic agent by loading anticancer drug doxorubicin (DOX) to GQD's surface and conjugating Cy5.5 (Cy) dye to GQD though a cathepsin D-responsive (P) peptide. Such type of agents demonstrated superior therapeutic performance both in vitro and in vivo because of the improved tissue penetration and cellular uptake. More importantly, they are capable of functioning as probes for programmed tracking the delivery and release of anticancer drug as well as drug-induced cancer cell apoptosis through GQD's, DOX's, and Cy's charateristic fluorescence, respectively.

A colorimetric fluorescent probe with fluorescence emission feature sensitive to SO2 derivatives, i.e. bisulfite (HSO3 −) and sulfite (SO3 2−), was developed based on the HSO3 −/SO3 2−-mediated nucleophilic addition reaction of the probe that. This probe exhibited SO3 2− sensing ability with detection limit down to 46 nM and desired selectivity over other reference anions and redox species. The preliminary fluorescence bioimaging experiments have validated the practicability of the as-prepared probe for SO2 derivatives sensing in living cells.

A new type of phosgene probe with a limit of detection down to 0.12 nM, response time of less than 1.5 s, and high selectivity over other similarly reactive toxic chemicals was developed using ethylenediamine as the recognition moiety and 8-substituted BODIPY unit as the fluorescence signaling component. The probe undergoes sequential phosgene-mediated nucleophilic substitution reaction and intramolecular cyclization reaction with high rate, yielding a product with the intramolecular charge transfer (ICT) process from amine to the BODIPY core significantly inhibited. Owing to the emission feature of 8-substituted BODIPY that is highly sensitive to the substituent's electronic nature, such inhibition on the ICT process strikingly generates strong fluorescence contrast by a factor of more than 23 300, and therefore creates the superhigh sensitivity of the probe for phosgene. Owing to the high reactivity of ethylenediamine of the probe in nucleophilic substitution reactions, the probe displays a very fast response rate to phosgene.

Rationale: Potential adverse effects of fluoride on neurodevelopment has been extensively explored and mitochondria have been recognized as critical targets. Mitochondrial biogenesis serves a crucial role in maintaining mitochondrial homeostasis and salubrious properties of resveratrol (RSV) has been well-defined. However, the molecular mechanisms governing mitochondrial biogenesis in developmental fluoride neurotoxicity remain unclear and the related therapeutic dietary agent is lacking. Methods: In vitro neuroblastoma SH-SY5Y cells and in vivo Sprague-Dawley rat model of developmental fluoride exposure were adopted. A total population of 60 children under long-term stable fluoride exposure were also recruited. This work used a combination of biochemical and behavioral techniques. Biochemical methods included analysis of mitochondrial function and mitochondrial biogenesis, as well as mRNA and protein expression of mitochondrial biogenesis signaling molecules, including silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Behavioral studies investigated spatial learning and memory ability of rats. Results: Both in vivo and in vitro experiments showed that sodium fluoride (NaF) caused mitochondrial dysfunction and impaired mitochondrial biogenesis. Also, NaF elevated SIRT1 levels and suppressed SIRT1 deacetylase activity along with decreased levels of PGC-1α, NRF1 and TFAM, suggestive of dysregulation of mitochondrial biogenesis signaling molecules. Moreover, enhancement of mitochondrial biogenesis by TFAM overexpression alleviated NaF-induced neuronal death through improving mitochondrial function in vitro. Further in vivo and in vitro studies identified RSV, the strongest specific SIRT1 activator, improved mitochondrial biogenesis and subsequent mitochondrial function to protect against developmental fluoride neurotoxicity via activating SIRT1-dependent PGC-1α/NRF1/TFAM signaling pathway. Noteworthy, epidemiological data indicated intimate correlations between disturbed circulating levels of mitochondrial biogenesis signaling molecules and fluoride-caused intellectual loss in children. Conclusions: Our data suggest the pivotal role of impaired mitochondrial biogenesis in developmental fluoride neurotoxicity and the underlying SIRT1 signaling dysfunction in such neurotoxic process, which emphasizes RSV as a potential therapeutic dietary agent for relieving developmental fluoride neurotoxicity.

Emerging evidence suggests environmental contaminant exposures during critical windows of development may contribute to the increasing prevalence of obesity. It has been shown that early life polybrominated diphenyl ethers exposures have critical impacts on child weight trajectories, however, little is known about their maternal mechanisms responsible for offspring obesity development. In this study, we investigated the effects of perigestational low-dose 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) exposure on maternal metabolome, and its possible link to adult offspring bodyweight changes. Female Sprague-Dawley rats were exposed to daily doses of 0.1, or 1 mg/kg BDE-47 from 10 days prior to conception until offspring were weaned on postnatal day 21, and then a gas chromatography-mass spectrometry based metabolomics analysis was used to uncover the global metabolic response in dams. The pups continued to grow into adulthood for measurements of bodyweight. Perigestational BDE-47 exposure caused increased adult bodyweight in male but not in female offspring and dams. Metabolomics revealed significant changes in maternal serum metabolites that clearly distinguish BDE-47 from control rats. These differentially expressed metabolites were primarily implicated in amino acid, lipid, carbohydrate, and energy metabolisms, which was confirmed by pathway analysis. Importantly, most of these identified metabolites were decreased, a state similar to maternal malnutrition that can predispose adult male offspring to weight increase and adiposity in a postnatal environment with abundant calories. Collectively, our data suggest that perigestational exposure to low-dose BDE-47 produces altered maternal serum metabolome, which may be an additional contributing factor to weight gain in adult male offspring.

A new type of Eu-based metal organic framework (Eu-MOF) characterized with ability of arsenate ion luminescence sensing and entrapping was constructed via solvothermal method based on the optimization of the organic ligand. The Eu-MOF aqueous dispersion sample displayed arsenate-triggered augment in luminescence emission intensity with appreciable contrast and detection sensitivity with limit of detection down to 17.8 nM toward arsenate ion, which is less than one-fourth of the upper limit concentration of arsenic in drinking water that the World Health Organization (WHO) set for public health, 72 nM. Additionally, the excellent recognition specificity Eu-MOF toward arsenate species over various potential interfering anions and cations was also confirmed. The rapid adsorption ability of Eu-MOF nanostructures toward arsenate in aqueous milieu that plausibly originated from its nature of chemical adsorption and the adsorption feature conforming to the Langmuir model was also verified. The advantages that Eu-MOF nanostructure displays in terms of high sensitivity and recognition specificity in luminescence sensing of arsenate ion and the desired arsenate entrapping ability in aqueous milieu is expected to impart it potential for sensing and entrapping trace amount of arsenate in water in practical applications.

Soil erodibility (K) is a key factor in predicting the erosion of soil by water. K is spatially influenced by many environmental factors, but studies of the scales of factors influencing K are rare. The objective of this study was to identify the scale-dependent relationships between K and various environmental factors using multivariate empirical mode decomposition (MEMD). K and nine environmental factors were investigated at 101 locations along a 4200-km sinuous transect in southeastern China and then they were decomposed and analyzed using MEMD. Mean K was 0.043 ± 0.008 t ha h MJ−1 mm−1 ha−1 and had a weakly moderate spatial variability. Six intrinsic mode functions (IMFs) and a residue were obtained for K and the environmental factors after decomposition. The mean scales for IMF1 to IMF6 were 123.4, 192.4, 347.0, 598.9, 1268.3 and 1559.2 km, respectively. IMF1 for each variable explained most of the spatial variability for the variable, and IMF1 and IMF2 or IMF1 and IMF3 explained half of the spatial variability of the variable. K was mainly associated with soil-particle composition and soil organic-matter content at small scales (IMF1-IMF2), with soil-particle composition and pH at moderate scales (IMF3-IMF4) and with elevation, saturated hydraulic conductivity and clay content at large scales (IMF5-IMF6). Modeled prediction functions of K at each scale of decomposition were accurate, but the total prediction accuracy at the sampling scale was slightly lower than for multiple linear regression. The MEMD method was nevertheless valuable and provided detailed information about the factors influencing K at different spatial scales.

Advanced fluorescence microscopy including single-molecule localization-based super-resolution imaging techniques requires bright and photostable dyes or proteins as fluorophores. The photophysical properties of fluorophores have been proven to be crucial for super-resolution microscopy’s localization precision and imaging resolution. Fluorophores TAMRA and Atto Rho6G, which can interact with macrocyclic host cucurbit[7]uril (CB7) to form host-guest compounds, were found to improve the fluorescence intensity and lifetimes of these dyes. We enhanced the localization precision of direct stochastic optical reconstruction microscopy (dSTORM) by introducing CB7 into the imaging buffer, and showed that the number of photons as well as localizations of both TAMRA and Atto Rho6G increase over 2 times.

As a typical kind of endogenous reactive nitrogen species, peroxynitrite (ONOO−) is believed heavily involved in the pathogenesis of many diseases such as inflammation, neurodegenerative conditions, and cardiovascular disorders. Precisely estimating ONOO− level in cell compartments is crucial for unraveling the biological relevance of ONOO− and enabling effective control of ONOO−-associated pathogenicity but suffers from serious difficulty owing to the daunting elusive features of ONOO−, namely nanomolar level physiological concentration and millisecond level biological half-life. A new fluorescent probe capable of detecting ONOO− with limit of detection down to 1.2 nM, response time less than 1s, and high recognition specificity over other similarly interfering species was developed in this work. For the probe constructed by conjugating an isatin moiety with an electron-withdrawing tricyanofuran (TCF) moiety, the former enabled a highly selective ONOO−-mediated oxidative decarbonylation reaction while the latter significantly improved the electrophilicity of the 3-position carbonyl group of isatin moiety and therefore accelerate the ONOO−-mediated nucleophilic attack, which eventually enabled prompt and efficient recognition reaction. For the decarbonylated product featured with a released primary aniline moiety, TCF acted as an acceptor for enabling an intramolecular charge transfer (ICT) process and the remarkable change in electronic feature upon reaction with ONOO−, which generated turn-on fluorescence with large contrast and therefore the basis for ONOO− sensing. The cell fluorescence imaging performed in this work definitely verified the capability of the probe for mapping intracellular ONOO−, despite the daunting elusive features of such physiological species.

In recent years, under the influence of the continuous reform of the education system, colleges and universities have set off a large-scale teaching reform, which also includes college English education. With the wide application of computer information technology and network technology, many English teachers have joined a new technological revolution in order to carry out English teaching with the help of computer information technology and network technology, thus promoting the improvement of teaching quality and efficiency.

Evidence demonstrates that 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) is able to disturb thyroid hormones (THs) homeostasis, yet the mechanisms remain unknown. We sought to investigate the effects of PBDE-47 on endoplasmic reticulum (ER) and lysosomes in thyroids. Using female Sprague-Dawley rats orally administered PBDE-47 at environmentally relevant doses (0.1, 1.0, 10 mg/kg/day) beginning ten days before breeding and ending at weaning, we showed that perinatal PBDE-47 exposure resulted in a reduction in serum THs levels and relative thyroid weight in adult female rats. These were accompanied by thyroid structural abnormalities with cell apoptosis. Mechanistically, PBDE-47 caused ER stress and activation of unfolded protein response (UPR). Moreover, PBDE-47 elicited lysosomal membrane permeabilization and the release of cathepsin. Importantly, the apoptotic cells co-localized with IRE1α, a stress sensor protein of UPR branch that mediates ER stress-induced apoptosis, or cathepsin B, a lysosomal cysteine protease that is involved in thyroglobulin, the precursor of THs, degradation and apoptosis induction. Interestingly, thyroglobulin was accumulated and predominantly presented in cells harboring compromised ER or lysosomal activity. Collectively, our findings suggest that perinatal low-dose PBDE-47 exposure hampers thyroglobulin turnover and induces thyroid cell apoptosis by triggering ER stress and lysosomal destabilization contributing to thyroid toxicity in adult female rats.

Fluoride neurotoxicity is associated with mitochondrial disruption. Mitochondrial fission/fusion dynamics is crucial to maintain functional mitochondria, yet little is known about how fluoride perturbs this dynamics and whether such perturbation contributes to impaired neurodevelopment. Here in human neuroblastoma SH-SY5Y cells treated with sodium fluoride (NaF, 20, 40 and 60 mg/L), mitochondrial fission suppression exerted a central role in NaF-induced mitochondrial abnormalities and the resulting autophagy deficiency, apoptosis augmentation, and compromised neuronal survival. Mechanically, pharmacological inhibition of mitochondrial fission exacerbated NaF-induced mitochondrial defects and cell death through promoting apoptosis despite partial autophagy restoration. Conversely, genetic enhancement of mitochondrial fission alleviated NaF-produced detrimental mitochondrial and cellular outcomes by elevating autophagy and inhibiting apoptosis. Further suppressing autophagy was harmful, while blocking apoptosis was beneficial for cellular survival in this context. Consistently, using Sprague–Dawley rats developmentally exposed to NaF (10, 50, and 100 mg/L) from pre-pregnancy until 2 months of delivery to mimic human exposure, we showed that perinatal exposure to environmentally relevant levels of fluoride caused learning and memory impairments, accompanied by hippocampal mitochondrial morphological alterations manifested as fission suppression and fusion acceleration, along with defective autophagy, excessive apoptosis and neuronal loss. Intriguingly, the disturbed circulating levels of identified mitochondrial fission/fusion molecules were closely associated with intellectual loss in children under long-term environmental drinking water fluoride exposure. Collectively, our results suggest that mitochondrial fission inhibition induces mitochondrial abnormalities, triggering abnormal autophagy and apoptosis, thus contributing to neuronal death, and that the mitochondrial dynamics molecules may act as promising indicators for developmental fluoride neurotoxicity.

As a very sensitive technique, photoswitchable fluorescence not only gains ultrasensitivity but also imparts many novel and unexpected applications. Applications of near-infrared (NIR) fluorescence have demonstrated low background noises, high tissue-penetrating ability, and an ability to reduce photodamage to live cells. Because of these desired features, NIR-fluorescent dyes have been the premium among fluorescent dyes, and probes with photoswitchable NIR fluorescence are even more desirable for enhanced signal quality in the emerging optical imaging modalities but rarely used because they are extremely challenging to design and construct. Using a spiropyran derivative functioning as both a photoswitch and a fluorophore to launch its periodically modulated red fluorescence excitation energy into a NIR acceptor, we fabricated core-shell polymer nanoparticles exhibiting a photoswitchable fluorescence signal within the biological window (∼700-1000 nm) with a peak maximum of 776 nm. Live cells constantly synthesize new molecules, including fluorescent molecules, and also endocytose exogenous particles, including fluorescent particles. Upon excitation at different wavelengths, these fluorescent species bring about background noises and interferences covering nearly the whole visible region and therefore render many intracellular targets unaddressable. The oscillating NIR fluorescence signal with an on/off ratio of up to 67 that the polymer nanoparticles display is beyond the typical background noises and interferences, thus producing superior sharpness, reliability, and signal-to-noise ratios in cellular imaging. Taking these salient features, we anticipate that these types of nanoparticles will be useful for in vivo imaging of biological tissue and other complex specimens, where two-photon activation and excitation are used in combination with NIR-fluorescence photoswitching.

Cell surface carbohydrates play significant roles in many physiological processes and act as primary markers to indicate various cellular physiological states. The functions of carbohydrates are always associated with their expression and distribution on cell membranes. Based on our previous work, we found that carbohydrates tend to form clusters; however, the underlying mechanism of these clusters remains unknown. Through the direct stochastic optical reconstruction microscopy (dSTORM) strategy, we found that with the contributions of lipid raft as a stable factor and actin cytoskeleton as a restrictive factor, carbohydrate clusters can stably exist with restricted size. Additionally, we revealed that the formation of most carbohydrate clusters (Gal and GlcANc clusters) depended on the carbohydrate-binding proteins (i.e., galectins) cross-linking their specific carbohydrate ligands. Our results clarify the organizational mechanism of carbohydrates on cell surfaces from their formation, stable existence and size-restriction, which promotes a better understanding of the relationship between the function and distribution of carbohydrates, as well as the structure of cell membranes.

A new type of flavone-based fluorescent probe (DMAF) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids was developed. Such type of probe undergoes Cys/Hcy-mediated cyclization reaction with the involvement of its aldehyde group, which suppresses of the photoinduced electron transfer (PET) process of the probe molecule and consequently leads to the enhancement of fluorescence emission upon excitation using visible light. The formation of product of the Cys/Hcy-mediated cyclization reaction was confirmed and the preliminary fluorescence imaging experiments revealed the biocompatibility of the as-prepared probe and validated its practicability for intracellular Cys/Hcy sensing.

Hybrid fluorescent nanoparticles (NPs) capable of fluorescing near-infrared (NIR) light (centered ∼730 nm) upon excitation of 800 nm laser light were constructed. A new type of conjugated polymer with two-photon excited fluorescence (TPEF) feature, P-F8-DPSB, was used as the NIR-light harvesting component and the energy donor while a NIR fluorescent dye, DPA-PR-PDI, was used as the energy acceptor and the NIR-light emitting component for the construction of the fluorescent NPs. The hybrid NPs possess δ value up to 2.3 × 10(6) GM per particle upon excitation of 800 nm pulse laser. The excellent two-photon absorption (TPA) property of the conjugated polymer component, together with its high fluorescence quantum yield (ϕ) up to 45% and the efficient energy transfer from the conjugated polymer to NIR-emitting fluorophore with efficiency up to 90%, imparted the hybrid NPs with TPEF-based NIR-input-NIR-output fluorescence imaging ability with penetration depth up to 1200 μm. The practicability of the hybrid NPs for fluorescence imaging in Hela cells was validated.

A new type of ratiometric fluorescent probe capable of detecting Hg(2+) ions at nanomolar-concentration level with high selectivity was developed based on an indole-trizole-rhodamine triad and its practicability for intracellular Hg(2+) sensing was verified. The as-prepared fluorescent probe is capable of detecting Hg(2+) over other competing metal ions including Ag(+) with high selectivity. The synergistic effect of Hg(2+)-assisted conversion of the nonfluorescent ring-closed rhodamine moiety to the highly fluorescent ring-open form as well as the fluorescence signal amplification originating from the Förster resonance energy transfer (FRET) from indole-trizole conjugate to rhodamine moiety contributed to a detection limit of 11 nM of the probe for Hg(2+) sensing.

A pair of reversible photochemical reactions correlates their reactant and product specifically, and such a correlation uniquely distinguishes their correlated signal from others that are not linked by this reversible reaction. Here a nanoparticle-shielded fluorophore is photodriven to undergo structural dynamics, alternating between a green-fluorescence state and a red-fluorescence state. As time elapses, the fluorophore can be in either state but not both at the same time. Thus, the red fluorescence is maximized while the green fluorescence is minimized and vice versa. Such an antiphase dual-color (AD) corelationship between the red and green fluorescence maxima as well as between their minima can be exploited to greatly improve the signal-to-noise ratio, thus enhancing the ultimate detection limit. Potential benefits of this correlation include elimination of all interferences originating from single-color dyes and signal amplification of AD photoswitching molecules by orders of magnitude.

An anthranol derivative (DTDDP) and an anthraquinone derivative diastereomer (DDDP) without typical donor–acceptor (D–A) structural features were synthesized from 1,4-diaminoanthraquinone via a one-step reaction. The absorption and fluorescence emission properties of DTDDP and DDDP were investigated in common organic solvents with different polarity. In spite of a lack of apparent D–A structure, DTDDP exhibited apparent solvatochromic fluorescence emission with shift >80 nm in aprotic media. The linear correlation of the Stokes shift of DTDDP in a Lippert–Mataga plot was observed, and the change in the dipole moment of DTDDP upon excitation, 10.7 D, was determined. Time-dependent density functional theory (TDDFT) calculation confirmed the marked hole–electron separation of the excited DTDDP molecule as compared to that of the excited DDDP molecule. The experimental results and the theoretical calculation revealed the excited-state intramolecular charge-transfer nature of the emitting state of DTDDP molecu...

Carbohydrates are involved in various physiological and pathological activities including cell adhesion, signal transduction and tumor invasion. The distribution of carbohydrates is the molecular basis of their multiple functions, but remains poorly understood. Here, we employed direct stochastic optical reconstruction microscopy (dSTORM) to visualize the pattern of N-acetylglucosamine (N-GlcNAc) on Vero cell membranes at the nanometer level of resolution. We found that N-GlcNAcs exist in irregular clusters on the apical membrane with an average cluster area of about 0.37 μm(2). Most of these N-GlcNAc clusters are co-localized with lipid rafts by dual-color dSTORM imaging, suggesting that carbohydrates are closely associated with lipid rafts as the functional domains. Our results demonstrate that super-resolution imaging is capable of characterizing the distribution of carbohydrates on the cellular surface at the molecular level.

In the logistics system, distribution process plays a very important role, whether the distribution route was reasonable arranged influences the cost of distribution and benefit. The optimization of the route is affected by the customer's address and delivery time. Minimizing the transportation cost is the purpose of this paper when satisfying the customer's requirement. On this basis, the traffic conditions are introduced to optimize the distribution route, and the effectiveness of the algorithm is tested and verified by simulation

A new type of fluorescent probe capable of detecting Ag+ and Hg2+ in two independent channels was developed in the present work. Specifically, in CH3CN–MOPS mixed solvents with CH3CN/MOPS ratio (v/v) of 15/85, this type of probe fluoresced weakly, and the addition of Ag+ remarkably induced fluorescence enhancement of the probe. In CH3CN–MOPS mixed solvents with the percentage of CH3CN increased up to 65%, the probe was highly fluorescent and addition of Hg2+ dramatically induced the fluorescence quenching. Thus, using such single-fluorophore-based probe and tuning the polarity of the mixed solvent, Ag+, and Hg2+ can be detected in independent channels with high selectivity and sensitivity. As a result, the mutual interference usually encountered in most cases of Ag+ and Hg2+ sensing owing to the similar fluorescence response that these two ions induced, can be effectively circumvented by using the probes developed herein.

Conjugated polymer nanoparticles (CPNs) were developed based on a polyfluorene-based conjugated polymer with thiophene units carrying pyridyl moieties incorporated in the backbone of polymer chains (PFPyT). Hybrid CPNs fabricated from PFPyT and an amphiphilic polymer (NP1) displayed pH-sensitive fluorescence emission features in the range from pH 4.8 to 13, which makes them an attractive nanomaterial for wide range optical sensing of pH values. The fluorescence of hybrid CPNs based on chemically close polyfluorene derivatives without pyridyl moieties (NP3), in contrast, remains virtually unperturbed by pH values in the same range. The fluorescence emission features of NP1 underwent fully reversible changes upon alternating acidification/basification of aqueous dispersions of the CPNs and also displayed excellent repeatability. The observed pH sensing properties of NP1 are attributed to protonation/deprotonation of the nitrogen atoms of the pyridine moieties. This, in turn, leads to the redistribution of electron density of pyridine moieties and their participation in the π-conjugation within the polymer main chains. The optically transparent amphiphilic polymers also exerted significant influence on the pH sensing features of the CPNs, likely by acting as proton sponge and/or acid chaperone.

DFT (U)B3LYP/6-311+G(d,p) calculations have been carried out to investigate the competing mechanisms and regioselectivity of the intermolecular radical anion [2+2] cycloadditions of phenyl vinyl sulfone with enones. The dominating pathways of the cycloadditions are verified by comparing the activation barriers. The regioselectivity is found to be mainly caused by the p–π conjugation at one end of the C C double bond.

Density functional theory calculations have proven the polar nature of the crossed intermolecular radical anion cycloadditions of various enones. The substituent effects on the chemo- and stereoselectivity of the cycloadditions have been elucidated. The electronic structures of the substituents strongly influence the formation of the radical anion and the reactivity of cycloaddition. The amino and nitryl substituents are both unfavorable for the cycloaddition. The cycloaddition is sensitive to the substituents on the C atoms which form a σ bond in the first cycloaddition step by both steric hindrance and electronic effect. To improve the chemoselectivity, one of these C atoms should be unsubstituted. The stereoselectivity mainly caused by the difference in steric interaction between the trans and cis transition states is benefited by the bulky substituents on the carbonyl.

Bromine-functionalized polythiophene (P3BrHT) block copolymers with different block ratios were synthesized and their micro-phase separation features in the solid state that allow for retaining molecular packing identities of the unmodified polythiophene (P3HT) were experimentally confirmed.

Hybrid fluorescent nanoparticles (NPs) were developed on the basis of a series of chemically close polyfluorene-based conjugated polymers and an amphiphilic polymer. NPs constructed from polyfluorene with 2,1,3-benzothiadiazole units incorporated in the backbone of polymer chains displayed Ag+-sensitive fluorescence emission features with high selectivity, which was demonstrated to be attributable to Ag+-induced aggregation and fluorescence quenching. The negatively charged sulfonic acid groups of amphiphilic polymer components located on the surfaces of the hybrid NPs and therefore provided binding sites for metal ions, which was found indispensable for the observed silver ion sensing features of the as-prepared hybrid NPs. Additionally, it was demonstrated that the benzothiadiazole-containing conjugated polymer components not only acted as the fluorescence signaling source but also participated in the metal binding/recognition processes. Thus, a mechanism of cooperative recognition-based aggregation-induced fluorescence static quenching and Ag+-triggered fluorescence dynamic quenching responsible for the observed Ag+ sensing results was confirmed.

Core-shell polymeric nanoparticles (NPs) containing photoswitchable spiropyrans (SP) and spirooxazines (SO) within the cores were fabricated. Fluorescence photoswitching studies revealed that the substituent groups on the photochromic SP/SO structures exerted significant influence on the fluorescence photoswitching behaviors of the as-prepared polymeric NPs, such as the reversibly interchangeable fluorescence color and the photoswitching kinetics. The electron-releasing and electron-withdrawing abilities of the substituent groups are believed to play important roles in controlling the electron configuration of the photochromic component and therefore be responsible for the tunable dual-color photoswitching performance.

A colorimetric fluorescent probe with fluorescence emission feature sensitive to SO

Carbohydrates on the cell surface control intercellular interactions and play a vital role in various physiological processes. However, their systemic distribution patterns are poorly understood. Through the direct stochastic optical reconstruction microscopy (dSTORM) strategy, we systematically revealed that several types of representative carbohydrates are found in clustered states. Interestingly, the results from dual-color dSTORM imaging indicate that these carbohydrate clusters are prone to connect with one another and eventually form conjoined platforms where different functional glycoproteins aggregate (e.g., epidermal growth factor receptor, (EGFR) and band 3 protein). A thorough understanding of the ensemble distribution of carbohydrates on the cell surface paves the way for elucidating the structure-function relationship of cell membranes and the critical roles of carbohydrates in various physiological and pathological cell processes.

Precisely identifying biological targets and accurately extracting their relatively weak signals from complicated physiological environments represent daunting challenges in biological detection and biomedical diagnosis. Fluorescence techniques have become the method of choice and offer minimally invasive and ultrasensitive detections, thus, providing a wealth of information regarding the biological mechanisms in living systems. Despite fluorescence analysis has advanced remarkably, conventional detections still encounter considerable limitations. This stems from the fact that the fluorescence intensity signal (I) is sensitive and liable to numerous external factors including temperature, light source, medium characteristics, and dye concentration. The interferences exasperatingly undermine the precision of measurements, and frequently render the signal undetectable. For example, fluorescence from single-molecule emitters can be measured on glass substrates under optimum conditions, but single-molecule events in complicated physiological environments such as live cells can hardly be detected because of autofluorescence interference and other factors. Furthermore, traditional intensity (I) and wavelength (λ) measurements do not reveal the interactive nature between the donor and the acceptor. Thus, innovative detection strategies to circumvent these aforementioned limitations of the conventional techniques are critically needed. With the use of photoswitching-induced donor-acceptor-fluorescence double modulations, we present a novel strategy that introduces three additional physical parameters: modulation amplitude (A), phase shift (ΔΦ), and lock-in frequency (ω), and demonstrate that such a strategy can circumvent the limitation of the conventional fluorescence detection techniques. Together, these five physical quantities (I, λ, A, ΔΦ, ω) reveal insightful information regarding molecular interactive strength between the probe and the analyte and enable extracting weak-fluorescence spectra from large interfering noises in complex environments.

A spironaphthoxazine (SO) photoswitch was synthesized, and its photochromic behaviors were investigated. SO underwent reversible ring-opening/closure isomerization between a spirocyclic isomer (closed form) and a merocyanine (MO isomer, open form) upon ultraviolet light irradiation. For the model SO in this work, the thermal equilibrium is substantially shifted toward the spirocyclic isomer even at -30.0° C. However, addition of zinc, as Zn(ClO 4)2, exerted an important effect on the thermal reversion process from the open (MO) to the closed form (SO). Kinetic analysis showed that thermal reversion with zinc is retarded more than 13-fold, significantly improving bistability. Moreover, introduction of zinc to the spirooxazine-merooxazine (SO-MO) system resulted in a new absorption band readily distinguishable from the bands arising from spirooxazine and merooxazine. For the first time, to the best of our knowledge, the microscopic rate constants for: MO photogeneration from SO (k1), thermal reversion of MO to SO (k2), complexation of MO with zinc (k 3) and for dissociation of the complex, MO-Zn (k4), as well as for the ionization equilibria of Zn(ClO4)2 have been evaluated. The preferred transoid structures of MO and those of MO-Zn derived from the preferred MO structures are considered. Although the kinetic study does not permit elucidation of the nature of zinc binding to MO to give MO-Zn, nor the precursor isomers of MO, a DFT calculational study in progress should shed light on the structure and relative stability of these essential intermediates.

This minireview highlights recent advances of research dedicated to photoswitchable fluorescent nanoparticles and their applications. Recently, several strategies have been developed to synthesize nanoparticles with optically switchable emission properties: either fluorescence on/off or dual-alternating-color fluorescence photoswitching. The underlying mechanisms of fluorescence photoswitching enable many different types of photoswitchable fluorescent nanoparticles to change fluorescence colors, thus validating the basis of the initial photoswitching design. Among all possible applications, the usage of photoswitchable fluorescent nanoparticles to empower super-resolution fluorescence imaging and to label biological targets was subsequently reviewed. Finally, we summarize the important areas regarding future research and development on photoswitchable fluorescent nanoparticles.

Although fluorescence offers ultrasensitivity, real-world applications of fluorescence techniques encounter many practical problems. As a noninvasive means to investigate biomolecular mechanisms, pathways, and regulations in living cells, the intrinsic heterogeneity and inherent complexity of biological samples always generates optical interferences such as autofluorescence. Therefore, innovative fluorescence technologies are needed to enhance measurement reliability while not compromising sensitivity. In this review, we present current strategies that use photoswitchable nanoparticles to address these real-world challenges. The unique feature in these photoswitchable nanoparticles is that fundamental molecular photoswitches are playing the critical role of fluorescence modulation rather than traditional methods like modulating the light source. As a result, new innovative technologies that have recently emerged include super-resolution imaging, frequency-domain imaging, antiphase dual-color correlation, etc. Some of these methods improve imaging resolution down to the nanometer level, while others boost the detection sensitivity by orders of magnitude and confirm the nanoparticle probes unambiguously. These enhancements, which are not possible with non-photoswitching molecular probes, are the central topics of this review.

A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.

Nanostructures with well-defined shape and highly monodisperse size were fabricated from model stilbazolium-like dyes with specific molecular structural and conformational characteristics. With the help of absorption and fluorescence optical spectroscopy, the correlated spectroscopy (COSY) and two- dimensional nuclear Overhauser effect spectroscopy (2D NOESY) techniques, along with X-ray diffraction (XRD) measurement, distinctively different aggregation processes of the model molecules are demonstrated. For model dye molecule with linear donor–π system–acceptor (D–π–A) structure, strong D–A pair, and planar conformation, specific intermolecular interaction was identified and special crystal structures as well as spectral properties were observed. For model dye molecules bearing nonlinear D–π–A–π–D structure, weak D–A pair but actual amphiphilic characteristics, a special aggregation process was confirmed and a focused size distribution of the produced nanostructures was obtained.

The nanoparticles of a copper phthalocyanine-fullerence dyad were prepared and the optical limiting properties of the nanoparticle dispersion were investigated. The nanoparticle sample (nanoparticle aqueous dispersion) exhibits an enhanced optical limiting performance as compared to the monomer sample (molecularly dispersed solution of CuPc-C60/THF). A mechanism based on the formation of ordered aggregates in the nanoparticles, which is expected to exert effect on the electronic structure of the system, is proposed for the nonlinear absorption enhancement of the nanoparticles.

Novel peony-like as well as actinia-like mesostructures were prepared from a stilbazolium-like dye by changing the quality of the solvent. The architecture evolutions of these mesostructures at the earlier stages of their formation confirm that the mesostructures result from multistage aggregation processes. Combining the results obtained from the correlated spectroscopy (COSY) and two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) experiments with those from the UV/vis absorption and fluorescence spectra, as well as the XRD measurements, possible formation mechanism based on different intermolecular interactions were proposed.

By ensemble and single molecule experiments, we confirmed that the magnetic field unequivocally exerted a positive effect on the fluorescence of dyes in dSTORM imaging.