Sensitive and accurate monitoring of urinary albumin and point-of-care testing using a fluorescent probe with anti-interference capacity against exogenous drugs.

Fluorescent probes have been reported for monitoring urinary albumin (u-ALB) to enable early diagnosis of kidney diseases and facilitate regular point-of-care testing (POCT) for chronic kidney disease (CKD) patients. However, the albumin can bind hydrophobic drugs through host-guest interactions, which may result in decreased accuracy of probes at regular drug sites and hamper POCT of albuminuria since CKD patients often need to take medications routinely. Herein, we reported a novel fluorescent probe (NC-2) by molecular engineering of a reported AIEgen (NC-1). The introduction of a non-conjugated ring moiety to the molecular rotor granted the NC-2 enhanced sensitivity with a limit of detection in urine of 8.7 mg/L, which is below l the threshold of microalbuminuria (30 mg/L). Moreover, the NC-2 was found to preferentially bind to the FA1 site of ALB, conferring it with excellent anti-interference capacities against exogenous drug molecules and metabolites. Simulation experiments using lab-spiked urine samples containing common drugs taken by CKD patients demonstrated that the probe could provide satisfied detecting accuracy (80-90 %). Furthermore, a paper-based device was constructed and achieved on-site detection of u-ALB in qualitative and semi-quantitative manners. Findings in this work were of great significance to the development of fluorescent probes for accurate detection of ALB in complex urine samples and the further achievement of fluorescence-based POCT for CKD.

Technology-based interventions on burden of older adults' informal caregivers: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: An increasing number of technologies are provided to reduce the burden of older adults' informal caregivers. However, less is known about the effects and the mechanism of technology to work on burden. This review is to evaluate the effectiveness of technology-based interventions (TBI) in alleviating the burden of older adults' informal caregivers and to distinguish its effective mechanism via group disparities. METHODS: A systematic review and meta-analysis of randomized controlled trials studies (RCTs) has been conducted. Web of Science, PubMed, EMBASE, Scopus, CINAHL, PsycINFO, WANFANG, CNKI, CQVIP databases, Cochrane Library Trials, and ClinicalTrials.gov were searched for trial studies and registry in both English and Chinese published from January 1990 to October 2022. Reviewers independently screened the articles and trials, conducted quality assessments, and extracted the data. All processes were guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias of the studies was evaluated by the Cochrane Systematic Review Handbook. The meta-analysis was conducted by RevMan 5.13. Subgroup analyses, sensitivity analyses, publication bias were also conducted. RESULTS: A total of 11,095 RCTs were initially screened, and 14 trials representing 1010 informal caregivers were included finally. This review proved TBI effective in reducing caregiving burden older adults. Subgroup analysis showed effects of TBI differed by interventions on control group and medical conditions of care recipients. CONCLUSION: TBI is an effective way to alleviate the burden on informal caregivers of aging people. Interventions for control groups and medical conditions of care-recipients are significant factors in effective interventions. Future researches could include more trials with high-quality or to explore more targeted aging groups, modalities of TBI, or caregiver outcomes. TRIAL REGISTRATION: The review protocol was registered on PROSPERO [CRD42021277865].

Polyhydroxy structure orchestrates the intrinsic antibacterial property of acrylamide hydrogel as a versatile wound-healing dressing.

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.

A novel dual-color fluorescent sensor with two pKas for on-site detection of pH in food.

Tracking pH fluctuations in food samples is important for ensuring food freshness. Fluorescent probes have been widely applied as promising tools for the on-site detection of pH changes; however, most of them can be applied only at either lower or higher pH ranges because their response structures commonly have a single acid dissociation constant (pKa). To address this problem, we designed a fluorescent sensor, called HMB, containing a methylpiperazine group with two pKa values, which exhibited a unique dual-color response to pH changes over a wide pH range. Furthermore, the HMB-based test strips are easily prepared and used as portable labels for the visual monitoring of food spoilage that results in microbial and anaerobic glycolytic pathways in real food (such as cheese and shrimp). To the best of our knowledge, this is the first fluorescent pH sensor with two pKa values, and we expect that this work will inspire more sensor designs for food quality control.

FRET-Based Host-Guest Supramolecular Probe for On-Site and Broad-Spectrum Detection of Pyrethroids in the Environment.

The massive use of pyrethroid pesticides in agriculture has brought growing concerns about food safety due to their several harmful effects on human health, especially through the accumulation of the food chain. To date, most of the available analytical methods for pyrethroids still suffer from insufficient detection universality, complicated sample pretreatment, and detection processes, which severely limit their practical applications. Herein, a novel Förster resonance energy transfer (FRET)-assisted host-guest supramolecular nanoassembly is reported, for the first time, successfully realizing ratiometric fluorescent detection of pyrethroids in real samples through the indicator displacement assay (IDA) mechanism. This method is capable of detecting a broad spectrum of pyrethroids, including bifenthrin, cyfluthrin, cypermethrin, deltamethrin, etofenprox, fenvalerate, and permethrin, with ultrahigh detection sensitivity, great selectivity, high anti-interference ability, and, in particular, distinct emission color response from red to green. Such a large chromatic response makes this method available for fast and on-site detection of pyrethroids in real samples with the aid of several simple portable analytical apparatuses.

Fast, portable, selective, and ratiometric determination of ochratoxin A (OTA) by a fluorescent supramolecular sensor.

Ochratoxin A (OTA), a mycotoxin found in various food items, possesses significant health risks due to its carcinogenic and toxic properties. Thus, detecting OTA is crucial to ensure food safety. Among the reported analytical methods, there has yet to be one that achieves fast, selective, and portable detection of OTA. In this study, we explore a novel supramolecular sensor, DOCE@ALB, utilizing human serum albumin as the host and a flavonoid fluorescent indicator as the guest. On the basis of indicator displacement assay, this sensor boasts an ultra-fast response time of just 5 s, high sensitivity with a limit of detection at 0.39 ppb, exceptional selectivity, and a noticeable ratiometric fluorescence response to OTA. This discernible color change and portability of the sensor make it suitable for on-site OTA detection in real food samples, including flour, beer, and wine, simply using a smartphone. In comparison to previously reported methods, our approach has showcased notable advantages in both response time and portability, addressing a critical need for food safety and regulatory compliance.

Recent Research Progress in Fluorescent Probes for Detection of Amyloid-ß In Vivo.

Alzheimer's disease (AD) is a neurodegenerative disease. Due to its complex pathological mechanism, its etiology is not yet clear. As one of the main pathological markers of AD, amyloid-ß (Aß) plays an important role in the development of AD. The deposition of Aß is not only related to the degeneration of neurons, but also can activate a series of pathological events, including the activation of astrocytes and microglia, the breakdown of the blood-brain barrier, and the change in microcirculation, which is the main cause of brain lesions and death in AD patients. Therefore, the development of efficient and reliable Aß-specific probes is crucial for the early diagnosis and treatment of AD. This paper focuses on reviewing the application of small-molecule fluorescent probes in Aß imaging in vivo in recent years. These probes efficiently map the presence of Aß in vivo, providing a pathway for the early diagnosis of AD and providing enlightenment for the design of Aß-specific probes in the future.

Recent Progress of Activity-Based Fluorescent Probes for Imaging Leucine Aminopeptidase.

Leucine aminopeptidase (LAP) is an important protease that can specifically hydrolyze Leucine residues. LAP occurs in microorganisms, plants, animals, and humans and is involved in a variety of physiological processes in the human body. In the physiological system, abnormal levels of LAP are associated with a variety of diseases and pathological processes, such as cancer and drug-induced liver injury; thus, LAP was chosen as the early biochemical marker for many physiological processes, including cancer. Considering the importance of LAP in physiological and pathological processes, it is critical that high-efficiency and dependable technology be developed to monitor LAP levels. Herein, we summarize the organic small molecule fluorescence/chemiluminescence probes used for LAP detection in recent years, which can image LAP in cancer, drug-induced liver injury (DILI), and bacteria. It can also reveal the role of LAP in tumors and differentiate the serum of cirrhotic, drug-induced liver injury and normal models.

Fast and sensitive detection of nitroxynil using a chalcone-based supramolecular fluorescent sensor.

Nitroxynil as a veterinary drug has been widely used for treatment of parasitic worms in food-producing sheep and cattle. However, the residual nitroxynil in edible animal products can lead to severe adverse effects on human health. Thus, development of an effective analytical tool for nitroxynil is of great significance. In the present study, we designed and synthesized a novel albumin-based fluorescent sensor, which was capable of detecting nitroxynil with the fast response (<10 s), high sensitivity (limit of detection ∼8.7 ppb), high selectivity, and excellent anti-interference property. The sensing mechanism was clarified by using the molecular docking technique and mass spectra. Moreover, this sensor showed the detection accuracy comparable to standard HPLC method, and meanwhile exhibited much shorter response time and higher sensitivity. All the results demonstrated that this novel fluorescent senor could serve as a practical analytical tool for determination of nitroxynil in real food samples.

The first fluorescent sensor for the detection of closantel in meat.

Closantel is widely used in the management of parasitic infestation in livestock, but is contraindicated in humans due to its high toxic to human retina. Thus, development of a fast and selective method for the detection of closantel residues in animal products is highly needed yet still challenging. In the present study, we report a supramolecular fluorescent sensor for closantel detection through a two-step screening process. The fluorescent sensor can detect closantel with a fast response (<10 s), high sensitivity, and high selectivity. The limit of detection is 0.29 ppm, which is much lower than the maximum residue level set by government. Moreover, the applicability of this sensor has been demonstrated in commercial drugs tablets, injection fluids, and real edible animal products (muscle, kidney, and liver). This work provides the first fluorescence analytical tool for accurate and selective determination of closantel, and may inspire more sensor design for food analysis.

Smartphone-based on-site detection of hydrogen peroxide in milk by using a portable ratiometric fluorescent probe.

The on-site detection of hydrogen peroxide (H2O2) is important for maintaining food safety as the ingestion of H2O2 can lead to serious pathological conditions. However, most reported fluorescent probes require a fluorometer to ensure readable signal output and reliable detection result. Consequently, the fluorescent detection of H2O2 can be realized only within a standard laboratory setting. Herein, we report a novel supramolecular strategy that can successfully convert the typical off-on response to H2O2 into a ratiometric response, which allows the on-site detection of H2O2 when used in conjunction with a smartphone-based 3D-printed miniaturized testing system. This method has acceptable sensitivity, good anti-interference ability, and desirable accuracy compared to a standard detection method. More importantly, this portable ratiometric method can be used to detect H2O2 residue in commercial milk samples with the simple testing apparatuses.

Naphthalene-based fluorescent probe for on-site detection of hydrazine in the environment.

The widespread occurrence of hydrazine residues in the environment, including in water, soil, and organisms, is a potential health threat to humans. Therefore, the development of an efficient method for the detection of hydrazine in environmental samples is highly desirable although it poses a significant challenge. In this study, we designed and synthesized a series of naphthalene-based fluorescent dyes through structural engineering and developed a novel probe for hydrazine detection. The probe could provide a distinct fluorescence response toward hydrazine in aqueous solution with high sensitivity and selectivity. Moreover, paper-based test strips can be easily fabricated using this probe, enabling the portable on-site detection of hydrazine with the aid of a smartphone. Furthermore, we demonstrated that this probe is capable of recognizing hydrazine in various environmental samples, including water, soil, plants, and zebrafish embryos. This research provides a promising tool for the detection of hydrazine in the environment.

Azocalixarene-Based Supramolecular System for the Detection of Paraquat via an Improved Indicator Displacement Assay.

In view of the lethal toxicity of paraquat (PQ) on human health, herein, a simple indicator displacement assay (IDA) based on an azo-modified calixarene host (azoCX[4]) and a fluorophore guest (p-DPD) were elaborately constructed for PQ detection in environmental water samples and plant surfaces. The fluorescent signal of p-DPD in the probe can be quenched by azoCX[4] through a photon-induced electron transfer process and recovered upon the addition of PQ within 10 s. The detection range of the p-DPD@azoCX[4] probe was calculated to be 0.35-8 µM in the Tris-HCl buffer solutions (pH = 7.4). Moreover, this probe exhibited excellent detection selectivity toward PQ over five herbicides (glyphosate, bispyribac, atrazine, ametryn, and bensulfuron methyl), together with anti-interference abilities in the presence of inorganic ions (K+, Na+, Zn2+, Ni2+, Li+, F-, Cl-, Br-, CO32-, HCO3-, and NO3-) and amino acids (Asp, Arg, Glu, Ala, and Cys). Particularly, the probe was successfully used to detect PQ in real water samples with acceptable accuracy and showed potential applications for on-site detection with paper-based test strips and on the leaf surface. We believe that this simplified IDA-based probe provided an effective detecting tool for PQ, and the design strategy would guide the further development of new IDA sensing systems.

General Method for Pesticide Recognition Using Albumin-Based Host-Guest Ensembles.

The massive use of pesticides nowadays has led to serious consequences for the environment and public health. Fluorescence analytical methods for pesticides are particularly advantageous with respect to simplicity and portability; however, currently available fluorescence methods (enzyme-based assays and indicator displacement assays) with poor universality are only able to detect few specific pesticides (e.g., organophosphorus). Making use of the multiple flexible and asymmetrical binding sites in albumin, we herein report a set of multicolor albumin-based host-guest ensembles. These ensembles exhibit a universal but distinctive fluorescent response to most of the common pesticides and allow array-based identification of pesticides with high accuracy. Furthermore, the simplicity, portability, and visualization of this method enable on-site determination of pesticides in a practical setting. This albumin host strategy largely expands the toolbox of traditional indicator displacement assays (synthetic macrocycles as hosts), and we expect it to inspire a series of sensor designs for pesticide detection.

Rapid and ratiometric fluorescent detection of phosgene by a red-emissive ESIPT-based-benzoquinolone probe.

Phosgene is a highly toxic gas that poses a serious threat to human health and public safety. Therefore, it is of great importance to develop an available detection method enabling on-the-spot measurement of phosgene. In this paper, we report a novel ESIPT fluorescent probe for phosgene detection based on quinolone fluorophore. This probe exhibits rapid response (in 10 s), stable signal output (last for 10 min), high sensitivity (LOD âˆ¼ 6.7 nM), and distinct emission color change (red to green) towards phosgene. The sensing mechanism was investigated by using 1H NMR, HRMS and fluorescence lifetime techniques, confirming that the amidation reaction between phosgene and quinolone effectively suppressed the ESIPT process of probe. Eventually, this probe was fabricated into polymer nanofibers by electrospinning and successfully employed to monitor gaseous phosgene with high specificity. This work provided a promising analytical tool for rapid and ratiometric detection of phosgene both in solution and in the gas phase.

pH-Activatable Organic Nanoparticles for Efficient Low-Temperature Photothermal Therapy of Ocular Bacterial Infection.

Low-temperature photothermal therapy (PTT) systems constructed by integrating organic photothermal agents with other bactericidal components that initiate bacterial apoptosis at low hyperthermia possess a promising prospect. However, these multicomponent low-temperature PTT nanoplatforms have drawbacks in terms of the tedious construction process, suboptimal synergy effect of diverse antibacterial therapies, and high laser dose needed, compromising their biosafety in ocular bacterial infection treatment. Herein, a mild PTT nanotherapeutic platform is formulated via the self-assembly of a pH-responsive phenothiazinium dye. These organic nanoparticles with photothermal conversion efficiency up to 84.5% necessitate only an ultralow light dose of 36 J/cm2 to achieve efficient low-temperature photothermal bacterial inhibition at pH 5.5 under 650 nm laser irradiation. In addition, this intelligent mild photothermal nanoplatform undergoes negative to positive charge reversion in acid biofilms, exhibiting good penetration and highly efficient elimination of drug-resistant E. coli biofilms under photoirradiation. Further in vivo animal tests demonstrated efficient bacterial elimination and inflammatory mitigation as well as superior biocompatibility and biosafety of the photothermal nanoparticles in ocular bacterial infection treatment. Overall, this efficient single-component mild PTT system featuring simple construction processes holds great potential for wide application and clinical transformation.

A surfactant-assisted approach enables the fluorescence tracking of benfluralin in plants.

Developing an effective detection method for benfluralin (BFA) is of great significance, since BFA as most widely used herbicides can be bioaccumulated by aquatic organisms in environment, possessing potential risks to human health. Owing to aggregation-caused quenching effect, most fluorescent detection methods based on donor-acceptor organic fluorophores suffered from very low sensitivity towards BFA in water system, hampering the bioimaging application in plants. In this work, we reported a novel surfactant-assisted fluorescent probe enabling detection of BFA in water with a high sensitivity. The involvement of specific surfactant Triton X100 (TX100) could amplify the response signal of probe more than 100-fold. The detection limit for BFA was determined to be 80 nM, satisfying the environmental protection requirements. Moreover, we demonstrated applications of this strategy for the fluorescent imaging of BFA in plant. The absorbance of BFA into roots of Arabidopsis thaliana and castor seedlings was successfully observed based on this method.

A near-infrared dicyanoisophorone-based fluorescent probe for discriminating HSA from BSA.

Despite the rapid development of fluorescent probe techniques for the detection of human serum albumin (HSA), a probe that discriminates between HSA and bovine serum albumin (BSA) is still a challenging task, since their similar chemical structures. As a continuation of our work, herein, a dicyanoisophorone-based fluorescent probe DCO2 is systematically studied for discrimination of HSA from BSA. The photophysical and sensing performances of DCO2, including basic spectroscopic properties, sensing sensitivity, and selectivity, exhibits that DCO2 could selectively bind with HSA and display remarkable fluorescence enhancement (∼254-fold) at 685 nm. The gap of the fluorescent response of DCO2 between HSA and BSA is an obvious increase from 21% to 73% compared to the previous probe DCO1. The sensing mechanism was elucidated by Job's plot, displacement experiment, and molecular docking, suggesting that the specific response to HSA originated from the rigid donor structure and steric hindrance. DCO2 could be buried in the DS1 pocket of HSA, and only partly wedged into the DS1 pocket of BSA with exposing twisted N,N-diethylamino group outside. Application studies indicated that DCO2 has well detective behavior for HSA in the biological fluids. This work could provide a new approach to design HSA-specific near-infrared fluorescence probes.

Modulating donor of dicyanoisophorone-based fluorophores to detect human serum albumin with NIR fluorescence.

It is urgently needed to develop NIR-fluorescent probe for detection of human serum albumin (HSA) since the interference of short-wavelength-fluorescence from endogenous species in real serum and urine. However, most previous reports were located in the short-wavelength region (<600 nm). In this work, a series of dicyanoisophorone (DCO)-based fluorophores 1-4 with different donor groups have been designed and investigated. A systematic study of their photophysical properties has been carried out. Among these probes, 4 exhibited NIR emission with the highest fluorescence brightness and the most sensitive signal response to HSA. Further studies demonstrated that 4 could strongly bind into the DS1 pocket of HSA with a 1:1 ratio. Importantly, the method based on 4 has been proven to be capable of sensing HSA in real serum and urine samples.

Fluorescence discrimination of HSA from BSA: A close look at the albumin-induced restricted intramolecular rotation of flavonoid probe.

Discrimination of human serum albumin (HSA) from bovine serum albumin (BSA) based on the fluorescence probe technique is still challenging due to similar chemical structures. In this work, a novel flavonoid-based fluorescent probe AF is reported for successful discrimination of HSA from BSA. The sensing performances of probe, including sensing dynamic, sensitivity and selectivity, have been carefully studied. Moreover, sensing mechanism was elucidated by Job's plot, displacement experiment, and molecular docking, suggesting that the specific response to HSA originated from the albumin-induced restricted intramolecular rotation (RIR) of probe. This work may provide a simple way for designing of novel probes for HSA with high selectivity.