Strategies for measuring concentrations and forms of amyloid-ß peptides.

Alzheimer's disease (AD) is affecting more and more people worldwide without the effective treatment, while the existed pathological mechanism has been confirmed barely useful in the treatment. Amyloid-ß peptide (Aß), a main component of senile plaque, is regarded as the most promising target in AD treatment. Aß clearance from AD brain seems to be a reliably therapeutic strategy, as the two exited drugs, GV-971 and aducanumab, are both developed based on it. However, doubt still exists. To exhaustive expound on the pathological mechanism of Aß, rigorous analyses on the concentrations and aggregation forms are essential. Thus, it is attracting broad attention these years. However, most of the sensors have not been used in pathological studies, as the lack of the bridge between analytical chemist and pathologists. In this review, we made a brief introduce on Aß-related pathological mechanism included in ß-amyloid hypothesis to elucidate the detection conditions of sensor methods. Furthermore, a summary of the sensor methods was made, which were based on Aß concentrations and form detections that have been developed in the past 10 years. As the greatest number of the sensors were built on fluorescent spectroscopy, electrochemistry, and Roman spectroscopy, detailed elucidation on them was made. Notably, the aggregation process is another important factor in revealing the progress of AD and developing the treatment methods, so the sensors on monitoring Aß aggregation processes were also summarized.

Near-infrared dual-response fluorescent probe for detection of N2H4 and intracellular viscosity changes in biological samples and various water samples.

N2H4 is a common raw material used in the production of pesticides and has good water solubility, so it may contaminate water sources and eventually enter living organisms, causing serious health problems. Viscosity is an important indicator of the cellular microenvironment and an early warning signal for many diseases. The high reactivity of hydrazine depletes glutathione (GSH) in hepatocytes, causing oxidative stress ultimately leading to significant changes in intracellular viscosity and even death. Therefore, it is particularly important to develop an effective method to detect N2H4 and viscosity in environmental and biological systems. On this basis, we developed two fluorescent probes, BDD and BHD, based on xanthene and 2-benzothiazole acetonitrile. The experimental results show that BHD and BDD have good imaging capabilities for N2H4 in cells, zebrafish and Arabidopsis. BHD and BDD also showed sensitive detection and fluorescence enhancement in the near-infrared region when the intracellular viscosity was changed. Notably, the probe BDD has also successfully imaged N2H4 in a variety of real water samples.

A fluorescent probe for detecting H2O2 and delivering H2S in lysosomes and its application in maintaining the redox environments.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can be used as a marker for the occurrence of oxidative stress in the organism. Lysosomes serve as intracellular digestive sites, and when the concentration of H2O2 in them is abnormal, lysosomal function is often impaired, leading to the development of diseases. Hydrogen sulfide (H2S) acts as a gaseous signaling molecule that scavenges H2O2 from cells and tissues, thereby maintaining the redox environment of the body. However, most of the reported hydrogen peroxide fluorescent probes so far can only detect H2O2, but cannot maintain the intracellular redox environment. In this paper, an H2O2 fluorescent probe LN-HOD with lysosomal targeting properties was designed and synthesized by combining the H2O2 recognition site with a naphthylamine fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes shift (110 nm), high sensitivity and good H2S release capability. The probe LN-HOD can be used to detect H2O2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H2O2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H2S, it can help to remove excess H2O2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H2O2, which contributes to the in-depth study of the cellular microenvironment in organisms.

A biocompatible chitosan-based fluorescent polymer for efficient H2O2 detection in living cells and water samples.

As a biomarker of oxidative stress, hydrogen peroxide (H2O2) plays a complex role in organisms, including regulating cell signaling, respiration, the immune system, and other life processes. Therefore, it is important to develop a tool that can simply and effectively monitor H2O2 levels in organisms and the environment. In this work, naphthalene fluorophores with a borate structure were introduced into chitosan (CTS) azide, and a CTS-based fluorescence sensor (CTS-HP) was designed for sensitive H2O2 detection. The biocompatibility and degradability of CTS endowed CTS-HP with reduced biotoxicity compared with organic fluorescent dyes, and the substitution degree of fluorophores on the CTS chains was 0.703. The randomly coiled chain structure of the CTS-HP probe enabled the boronic acid recognition sites on the fluorophores to achieve the enrichment of analyte H2O2 through a synergistic effect. Therefore, the probe CTS-HP (10 µg mL-1) exhibited a 21-fold fluorescence enhancement and good detection limit (LOD = 8.98 nM) in H2O2 solution, reaching the maximum fluorescence response faster (within 16 min). The probe also successfully achieved the fluorescence imaging of endogenous and exogenous H2O2 in zebrafish and living cells and labeled the recovery experiment of H2O2 in real water samples (recoveries rates of 90.93-102.9 % and RSD < 3.09 %).

A water-soluble and biocompatible chitosan-based fluorescent probe for real-time monitoring formaldehyde in living cells and zebrafish.

Formaldehyde (HCHO) is a common environmental toxicant that can harm the human respiratory tract and nervous system when exposed for long period of time. As a carcinogen, HCHO also increases the risk of cancer in humans. HCHO can be produced endogenously in living systems and plays an essential role in physiological and biochemical reactions and pathogenesis. Therefore, monitoring the level of HCHO in vivo and in vitro has become the focus of attention. The designed naphthalene fluorophore was introduced onto modified chitosan to prepare a chitosan-based fluorescent probe (CS-FA) for HCHO detection. Compared to other small-molecule probe analogs for the detection of HCHO, the randomly coiled polymer chain of chitosan enabled CS-FA to "enrich" HCHO using the synergistic binding of hydrazino-naphthalimide recognition sites. Thus, the reaction of the analyte with the recognition site was accelerated, resulting in a faster equilibrium fluorescence response (2-3 min) and high sensitivity. In addition, the introduction of biomass material chitosan also improved the biocompatibility of the probe. Then a series of composite materials (test strips and hydrogel) were prepared based on the probe to expand the application form of the probe.

A turn-on fluorescent probe for sensing N2H4 in living cells, zebrafishes and plant root with a large turn-on fluorescence signal.

Hydrazine (N2H4) plays an important role in industrial production, but it is highly toxic, leaking or exposing it will pollute the environment and cause serious harm to human beings. Therefore, it is necessary to use a simple and effective method to detect N2H4 in environmental systems and organisms. Herein, a novel water-soluble fluorescent probe based on coumarin fluorophore, 2-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)isoindoline-1,3-dione (C-Z1), is reported. The fluorescence intensity of the probe at 530 nm was enhanced gradually with the addition of N2H4, and the maximum enhancement was about 28 times. The probe has good selectivity and sensitivity, the detection limit of hydrazine hydrate is 1.48 × 10-7 M, and the response mechanism of the probe is proved by theoretical calculation and experiment. C-Z1 has been shown to detect N2H4 in a variety of environmental samples, including water, soil, air, cells, zebrafish and plants. In addition, C-Z1 can be made into test strips for easy portability and used for rapid quantitative detection of N2H4 in the field by its distinct change in fluorescence color. Thus, C-Z1 has great potential for the analysis and detection of environmental contaminants.

A highly sensitive and low toxicity cellulose-based fluorescent polymer for H2S detection in cells, zebrafish and food samples.

A cellulose based polymer probe (HC-HS) was prepared for the detection of H2S. HC-HS can be applied to fluorescence imaging of H2S in living cells and zebrafish, and HC-HS was made into test strips to detect H2S produced in the process of food corruption.

Development of a two-photon fluorescent probe for imaging hydrogen sulfide (H2S) in living cells and zebrafish.

We present a new two-photon fluorescent probe (T-HS) for the detection of H2S. With the addition of hydrogen sulfide, the absorption and fluorescence spectra of the probe show regular changes. The probe exhibited favorable properties, such as large turn-on fluorescence signal, good selectivity and low cytotoxicity. Moreover, the probe T-HS was successfully used for the fluorescence imaging of H2S in live cells and zebrafish.

Construction of a water-soluble fluorescent probe for copper (II) ion detection in live cells and food products.

The quality of wine can be affected by excess Cu2+ due to the occurrence of oxidation reactions or precipitation. Therefore, it is essential to use simple and effective testing methods to ensure the Cu2+ content in wine. In this work, we designed and synthesized a rhodamine polymer fluorescent probe (PEG-R). The water solubility of PEG-R was improved by the introduction of polyethylene glycol, which improved the performance and broadened its application in the food field. The PEG-R was characterized by high sensitivity, selectivity and fast response to Cu2+ and was able to complete the response process within 30 s, with approximately 29-fold fluorescence enhancement of the probe after exposure to Cu2+, the limit of detection (LOD) was 1.295 × 10-6 M. The probe can be used for the determination of Cu2+ in living cells, zebrafish, white wine and food products, and it was made into practical gels and test strips.

Recent Studies on the Preparation and Application of Ionic Amphiphilic Lignin: A Comprehensive Review.

As the second most abundant natural polymer after cellulose, lignin has received considerable attention recently due to its reproducibility, safety, and biodegradability. Studies are now focusing on the development of new lignin applications to replace petroleum-based chemicals. Unfortunately, lignin has several inherent problems, such as poor water solubility and a tendency to agglomerate. However, after chemical modification, lignin can gain new functions through the introduction of new functional groups. For example, amphiphilic lignin is a polymer that is soluble in both water and organic solvents. Amphiphilic lignin polymers can be divided into anionic, cationic, and anionic-cationic amphoteric lignin-based polymers, according to the ions contained in their molecular structure. Amphiphilic lignin polymers also have a wide range of applications in various industrial fields and can be used as wetting agents, detergents, controlled release fertilizers, adsorbents, and emulsifiers. Thus, this article reviews research progress on the synthesis and applications of amphiphilic lignin-derived polymers over the past 10 years, providing a theoretical reference for the utilization of high-added-value and high-performance lignin.

Construction of a unique two-photon fluorescent probe and the application for endogenous CO detection in live organisms.

Carbon monoxide (CO) is one of the most significant signal molecules and plays an important role in regulating human physiological and pathological processes. In this study, a novel Pd-based complex (Pd-BNP-OH) was developed for endogenous CO detection. The structure and morphology of Pd-BNP-OH was characterized by SEM, XPS, and NMR analyses. When Pd-BNP-OH was reacted with CO, a strong fluorescence enhancement at 510 nm was observed. In addition, Pd-BNP-OH exhibited high stability and selectivity toward CO in PBS buffer. In biological experiments, Pd-BNP-OH exhibited little cytotoxicity in cellular environment, and a bright fluorescence turn on was observed in the presence of exogenous CO and endogenous generated CO. The probe was then applied for CO detection in live zebrafish by both one-photon and two-photon excitation. Significantly, Pd-BNP-OH has excellent two-photon property, controllable structure and high biocompatibility. These features enable the probe to detect endogenously generated carbon monoxide in live organisms successfully.

A biotin-guided two-photon fluorescent probe for detection of hydrogen peroxide in cancer cells ferroptosis process.

Hydrogen peroxide (H2O2) plays a vital role in organism due to its strong oxidizability, especially in resisting the invasion of pathogens. Cancer cells have abnormal concentrations of hydrogen peroxide due to their disordered reproduction. In complex biological systems, however, conventional fluorescent probes based solely on their fluorescent response to abnormal H2O2 overexpression in cancer cells are not enough to distinguish cancer cells from other unhealthy or immune cells. Therefore, it is necessary to develop other methods to allow the probe to selectively enter the cancer cells and perform fluorescence imaging of the hydrogen peroxide in the cancer cells. Herein, we developed a biotin-guided, two-photon fluorescent probe (BT-HP) for sensitive detection of H2O2 in cancer cells. Through the study on the properties of the probe, it was found that the probe can selectively enter cancer cells. The depth penetration imaging of H2O2 in cancer cells and tumor tissues by two-photon microscope proves the potential of the probe BT-HP as a tumor targeting H2O2 biosensor. The probe was further applied to detect hydrogen peroxide in cancer cells during the ferroptosis process.

Development of a novel NIR viscosity fluorescent probe for visualizing the kidneys in diabetic mice.

Viscosity is an important parameter for evaluating cell health, and abnormal viscosity can cause a variety of intracellular organelle function disorders. The mitochondria are a key organelle in cells, and the viscosity of the mitochondria determines the state of the cell. In this work, we report a novel near-infrared fluorescent probe, referred to as NI-VD, that has a large Stokes-shift and a satisfactory response multiple. NI-VD can sensitively detect changes in cell viscosity in cells and tissues, and it can effectively avoid interference from the overlap of excitation and emission light. The fluorescence spectrum shows that NI-VD has maximum emission peaks at 730 nm, and the fluorescence intensity is amplified with an increase in the solution viscosity. The response from pure PBS solution to glycerol changes by 13-fold. After confirmation in a variety of cell and biological models, NI-VD can detect the changes in viscosity in mitochondria. Most importantly, this study is the first to visualize the differences between the kidneys of diabetic mice and normal mice. This approach is a new solution for the diagnosis and treatment of diabetic nephropathy.

A fluorescent probe for specific detection of ß-galactosidase in living cells and tissues based on ESIPT mechanism.

ß-galactosidase is of great significance to living organisms, which is an important marker of primary ovarian cancer and cellular senescence. To detect the activity of ß-galactosidase, a novel fluorescent probe ESIPT-GAL which based on excited state intramolecular proton transfer (ESIPT) mechanism for detecting ß-galactosidase is developed in this work with low background fluorescence and high sensitivity (ΦF = 0.0045-0.2409). The fluorescence intensity at 552 nm of this probe increased by ~ 55 times with ß-galactosidase addition (0-4 U/mL), and its detection limit is very low (3.9 × 10-5 U/mL). In addition, the spectral data (pseudo-first-order rate: 1.303 min-1) and enzyme kinetic parameter (Vmax = 69.5 µΜ•S-1) both show that the probe can achieve rapid response to ß-galactosidase. Moreover, the probe has good water solubility, which ensures that it has good biocompatibility and can be easily applied to detect ß-galactosidase in living cells and tissues. Importantly, the probe ESIPT-GAL can monitor ß-galactosidase in deep mouse tissue sections (90 µm).

Construction of a dual-response fluorescent probe for copper (II) ions and hydrogen sulfide (H2S) detection in cells and its application in exploring the increased copper-dependent cytotoxicity in present of H2S.

Multiple types of metal ions and active small molecules (reactive nitrogen species, reactive oxygen species, reactive sulfur species, etc.) exist in living organisms. They have connections to each other and can interact and/or interfere with each other. To investigate the relationship of metal ions and active small molecules in living cells, it is necessary and critical to develop molecular tools that can track two kinds of associated certain metal ions and reactive molecules with multiple fluorescence signals. However, this is a challenging task that requires an ingenious molecular design to achieve this goal. Here, we present a fluorescent probe (D-CN) that can offer fluorescence imaging of H2S and copper (II) ions with different response signals. Recognition of H2S and Cu (II) by the new probe can result in green and red emissions, respectively, providing different signal responses to the two substances in living cells and zebrafish. In addition, we used this probe to visually prove that the cytotoxicity of copper ions in living cells increases in the presence of hydrogen sulfide and could lead to cell apoptosis.

A biotin-guided fluorescent probe for dual-mode imaging of viscosity in cancerous cells and tumor tissues.

A cancer cell targeted fluorescent viscosity probe has been designed and synthesized to specifically visualise viscosity changes in biotin receptor (BiR) positive cells over biotin negative cells via dual-mode fluorescence imaging: fluorescence intensity mode and fluorescence lifetime mode.

Single Fluorescent Probe Separately and Continuously Visualize H2S and HClO in Lysosomes with Different Fluorescence Signals.

A complicated relationship between the active small molecules exists in cells. On the organelle level, active small molecules also play an important role in the maintenance of organelle functions and roles. To investigate the relationship of biomolecules in subcellular, it is necessary and critical to develop molecular tools that can track two kinds of associated biomolecules within organelles with multiple fluorescence signals. However, this is still an unmet challenge up to date. Herein, we present the first single-fluorescent probe (Lyso-HA-HS) that can detect oxidative (HOCl) and reductive (H2S) substances within an organelle (lysosomes) with multiresponse signals. The reactions of the new probe with H2S and HOCl simultaneously result in the blue and red channels emissions, respectively, providing different signal responses to the oxidative and reductive substances in the cellular lysosomes. Using a single fluorescent probe, we first achieved dual-channel imaging of the endogenous hypochlorous acid and hydrogen sulfide, respectively, in the lysosomes in the living cells. Moreover, the highly desirable attributes of the probe Lyso-HA-HS (such as high selectivity, good membrane-permeability, and lysosome enrichment ability) may enable it to be used in revealing the relationship of HOCl and H2S in lysosomes.

Risk factors of surgical site infection in geriatric orthopedic surgery: A retrospective multicenter cohort study.

AIM: As we are experiencing the progressive aging of our population, risk management of geriatric orthopedic patients is extremely important. The present study was carried out to identify independent predictors of surgical site infection and to better define the threshold value of serum albumin on postoperative wound infection in older patients. METHODS: This retrospective multicenter study was carried out from January 2015 to June in 2017. A total of 3378 older patients (aged ≥60 years) were enrolled. We extracted the patients' demographics, characteristics of disease, treatment-related variables and indexes of laboratory examination. Receiver operating characteristic analysis was carried out to find the optimum cut-off value for serum albumin. Univariate and multivariate logistic analysis models were carried out, respectively, to determine independent predictors of surgical site infection. RESULTS: A total of 123 patients developed wound infection in the present study. Surgical site infection prolonged hospitalization of patients by a mean of 14.2 days. The overall incidence was 3.64%, with 0.47% for deep infection and 3.16% for superficial infection. Independent predictors of surgical site infection identified by multivariate analysis were traumatic injury (odds ratio 12.42, 95% CI 6.80-22.12; P = 0.000), serum albumin <32.6 g/L (odds ratio 2.54, 95% CI 1.22-5.29; P = 0.013) and American Society of Anesthesiologists physical status index class 3 or higher (odds ratio 2.14, 95% CI = 1.24-3.69; P = 0.006). CONCLUSIONS: We recommend that surgeons evaluate the nutritional status of older patients and optimize the perioperative strategy of supplementary nutrition support to reduce the risk of postoperative wound infection. Geriatr Gerontol Int 2019; 19: 213-217.

A photocaged fluorescent probe for imaging hypochlorous acid in lysosomes.

By combining the advantages of the photocaging technology and traditional analyte-responsive fluorescent probes, we designed and synthesized the first photocaged lysosomal-targeted fluorescent HOCl probe (PL-HA). The new caged PL-HA probe was capable of remote light-controlled recognition of HOCl in lysosomes.

A targetable fluorescent probe for real-time monitoring of fluoride ions in mitochondria.

Fluorion are pivotal anions in biology because they play an important role in dental care, treating osteoporosis, preventing tooth decay and promoting the healthy growth of bone. Studies have shown that high levels of fluoride will lead to the inactivation of the mitochondria. Therefore, it is urgent to develop a method to detect the fluoride anions in the mitochondria. Herein, we have developed a novel mitochondrial-target fluorescent probe for detecting F- in living cells. The probe exhibited excellent sensitivity and high selectivity for F- over the other relative species. With changing fluoride ions, the fluorescence spectrum of the probe changed significantly with a large turn-on fluorescence signal. Cell imaging indicated that the probe can penetrate viable cell membranes and rapidly detects and images fluorion over other anions in the mitochondria.