Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis.

The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.

Visualized Tracking and Multidimensional Assessing of Mitochondria-Associated Pyroptosis in Cancer Cells by a Small-Molecule Fluorescent Probe.

Pyroptosis is closely related to the development and treatment of various cancers; thus, comprehensive studies of the correlations between pyroptosis and its inductive or inhibitive factors can provide new ideas for the intervention and diagnosis of tumors. The dysfunction of mitochondria may induce pyroptosis in cancer cells, which can be reflected by the fluctuations of the microenvironmental parameters in mitochondria as well as the changes of mitochondrial DNA level and morphology, etc. To precisely track and assess the mitochondria-associated pyroptosis process, simultaneous visualization of changes in multiphysiological parameters in mitochondria is highly desirable. In this work, we reported a nonreaction-based, multifunctional small-molecule fluorescent probe Mito-DK with the capability of crosstalk-free response to polarity and mtDNA as well as mitochondrial morphology. Accurate assessment of mitochondria-associated pyroptosis induced by palmitic acid/H2O2 was achieved through monitoring changes in mitochondrial multiple parameters with the help of Mito-DK. In particular, the pyroptosis-inducing ability of an antibiotic doxorubicin and the pyroptosis-inhibiting capacity of an anticancer agent puerarin were evaluated by Mito-DK. These results provide new perspectives for visualizing mitochondria-associated pyroptosis and offer new approaches for screening pyroptosis-related anticancer agents.

Investigating Oxidative Stress Associated with Myocardial Fibrosis by High-Fidelity Visualization and Accurate Evaluation of Mitochondrial GSH Levels.

Myocardial fibrosis is frequently accompanied by elevated levels of oxidative stress. Mitochondrial glutathione (mGSH), an essential biomolecule for maintaining redox homeostasis in mitochondria, could serve as an effective indicator for investigating the oxidative stress associated with myocardial fibrosis. In this study, a ratiometric fluorescent probe named Mito-NS6, capable of being anchored in mitochondria and reversibly responding to GSH with an appropriate dissociation equilibrium constant, was rationally designed and utilized to visualize and evaluate the changes of mGSH levels caused by oxidative stress in myocardial fibrosis. Benefiting from the good performance of Mito-NS6, we successfully achieved the quantification of mGSH in cardiac fibroblasts using a confocal laser-scanning microscope, revealing that salvianolic acid B (SalB) can act as an effective drug to alleviate myocardial fibrosis through depressing oxidative stress. Moreover, we employed ratio fluorescence imaging to track the fluctuation in GSH levels within a mice model of myocardial fibrosis induced by isoproterenol and found that myocardial fibrosis caused a higher oxidative stress level in myocardial tissue as well as heart organs. These results provide a novel point of view for the diagnosis and treatment of myocardial fibrosis.

The silent reservoir? SARS-CoV-2 detection in the middle ear effusion of patients with Otitis media with effusion after omicron infection.

PURPOSE: This multicenter, prospective study is designed to investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the Middle Ear Effusion (MEE) of patients developing Otitis Media with Effusion (OME) subsequent to an Omicron infection. The objective is to elucidate any potential association between the virus and the condition. METHODS: This study, conducted from January to June 2023, spanned the Otolaryngology departments of two medical institutions in Eastern China. Patients manifesting OME subsequent to Omicron infection from both hospitals were subjected to comprehensive otolaryngological assessments, including pure-tone audiometry (PTA), tympanometry, otoscopic examination, and nasopharyngolaryngoscopy. Subsequently, MEE samples extracted from these patients were analyzed through RT-PCR to detect SARS-CoV-2. RESULTS: In this study, 23 patients (32-84 years; 57.5 ± 14.8 mean age; 47.8 % male) presented OME in 25 ears post-Omicron infection, with 21 (91.3 %) exhibiting unilateral symptoms. The median duration from infection to MEE sampling was 21 days (IQR: 25-46; range: 11-150). Predominantly, 64.0 % exhibited Type B tympanograms, and fluid accumulation was observed in 88.0 % of ears. SARS-CoV-2 was detected in 3 MEE samples (12.0 %), with cycle threshold values ranging between 25.65 and 33.30. CONCLUSIONS: Our study highlights the potential effects of COVID-19 on the middle ear, suggesting a link between SARS-CoV-2 and OME onset. The virus, a significant contributor to OME, is detectable in the MEE nearly a month post-Omicron infection, indicating a potential alteration in OME treatment strategies and a risk of recurrence, emphasizing the necessity for otolaryngologist vigilance.

Accurate Detection of Hcy in Human Serum and Two-Photon Visualization of Atherosclerosis Using a Highly Specific Fluorescent Probe.

As an important metabolic intermediate of sulfur-containing amino acids in human body, homocysteine (Hcy) is regarded as an independent risk factor for atherosclerotic cardiovascular disease. Therefore, real-time monitoring of the fluctuation of Hcy level is of great importance for the early diagnosis as well as the treatment of atherosclerosis. Herein, a new two-photon (TP) fluorescent probe (RH-2) was developed via a hydrogen bond-assisted strategy, which had a high specificity for detecting Hcy over cysteine (Cys) and glutathione (GSH) in solution, cells, and tissue. Probe RH-2 was applied to the quantitative determination of Hcy in human serum successfully. Moreover, the two-photon fluorescence (TPF) imaging of abnormal expression of Hcy in aortic vessels and liver of atherosclerotic model mice were fulfilled by RH-2. Therefore, probe RH-2 can be served as a potential tool to understand the function of Hcy in atherosclerosis, supplying a clinical promise for the early diagnosis of atherosclerosis (AS).

Towards a tapered Yb-doped fiber-based narrow linewidth single-mode fiber laser with a high signal to Raman ratio.

We demonstrate an all-fiber high-power narrow-linewidth fiber laser based on a homemade tapered Yb-doped fiber (T-YDF). The laser performance is investigated and systematically compared with different seed powers and pump manners. The experimental results reveal that the injected seed power requires a trade-off designed to take into account the impact of spectral broadening, nonlinear effects, and transverse mode instability (TMI). Compared with the co-pump manner, the counter-pump manner performs well in inhibiting nonlinearities, spectral broadening, and improving the TMI threshold. Under the counter-pump manner, this narrow-linewidth T-YDF amplifier realized a 2.09 kW output power with a 3 dB spectral linewidth of ∼0.34 nm, a beam quality of M2∼1.28 and a high Raman suppression ratio over 53.5 dB, the highest reported power for such a T-YDF-based narrow-linewidth single-mode laser, to the best of our knowledge. This work provides a promising pathway towards implementing monolithic high-power narrow-linewidth single-mode fiber lasers.

Can SARS-CoV-2 positive pregnant women affect the hearing of their newborns: A systematic review.

The 2019 coronavirus disease (COVID-19) pandemic has caused over 500 million confirmed cases (including pregnant women) worldwide. Recently, hearing status in newborns born to mothers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has received attention. This systematic review outlines the current knowledge regarding the effects of maternal SARS-CoV-2 infection during pregnancy on newborn hearing. Intrauterine SARS-CoV-2 infection has the potential to affect the auditory system of the newborn due to intrauterine hypoxia and vertical transmission. SARS-CoV-2 might have a greater influence on hearing loss (HL) in newborns during the second and third trimesters of pregnancy. Therefore, all newborns whose mothers had COVID-19 during pregnancy should be evaluated for cochlear function, regardless of whether their mothers were symptomatic at the time of the disease. However, the understanding of this issue is not consistent and remains controversial. Since early identification and intervention of congenital HL are crucial to the language development of newborns, newborns should be provided with audiological evaluation by various approaches, including Tele-audiology, in the COVID-19 era.

An Oligopeptide-Protected Ultrasmall Gold Nanocluster with Peroxidase-Mimicking and Cellular-Imaging Capacities.

Recent decades have witnessed the rapid progress of nanozymes and their high promising applications in catalysis and bioclinics. However, the comprehensive synthetic procedures and harsh synthetic conditions represent significant challenges for nanozymes. In this study, monodisperse, ultrasmall gold clusters with peroxidase-like activity were prepared via a simple and robust one-pot method. The reaction of clusters with H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB) followed the Michaelis-Menton kinetics. In addition, in vitro experiments showed that the prepared clusters had good biocompatibility and cell imaging ability, indicating their future potential as multi-functional materials.

Accurate Monitoring and Multiple Evaluations of Mitophagy by a Versatile Two-Photon Fluorescent Probe.

Mitophagy plays a critical role in regulating and maintaining cellular functions, particularly regulating the quantity and quality of mitochondria. In this research, a multifunctional two-photon fluorescent probe Mito-PV with improved mitochondria-anchored ability was designed. The proposed probe can track the fluctuation of polarity and viscosity in mitochondria simultaneously with two well-distinguished emissions. It can also precisely visualize the change in mitochondrial morphology (including mitochondrial form factor and length). The real-time and accurate monitoring of mitophagy under two-photon excitation was successfully achieved by utilizing probe Mito-PV through supervising the alterations of diverse mitophagy-related parameters (including colocalization coefficient, polarity, viscosity, and mitochondrial morphology). In addition, probe Mito-PV can be applied to evaluate drug bpV(phen) as an effective mitophagy inhibitor. Therefore, our work may provide a more efficient and reliable method for precisely monitoring mitophagy from multiple evaluations.

Telemedicine for ear diseases with the smartphone otoscopes via WeChat in the COVID-19 era.

PURPOSE: This study aimed to evaluate the outcomes and satisfaction of ear patients who participated in the smartphone otoscopes telemedicine via WeChat. METHODS: Patients in this study included newly diagnosed outpatients and online patients who did not undergo an outpatient diagnosis. Patients performed regular ear self-examinations, took pictures at home using their smartphone endoscopes, and submitted images to a WeChat community. Otolaryngologist gave timely online feedback. All of the following data were recorded: patients age and gender, disease duration, outpatient diagnosis, side, telemedicine duration, number of telemedicine visits, outcomes, satisfaction. RESULTS: A total of 74 patients were included in the study, including 39 males and 35 females, with an average age of 31.1 ± 13.7 years (range 4-55 years). Of these patients, 68 were outpatients, and 6 directly participated in telemedicine online. The patient's disease duration ranged from 1 day to 15 days, with an average of 4.0 ± 3.0 days. The mean duration was 8.1 days (range: 3-21 days) for telemedicine. The mean number of visits was 2.7 times (range: 2-6 times) for telemedicine. 68 (91.9%) of the 74 patients were cured, 6 (8.1%) were improved, and 0 (0%) were ineffective. Almost all patients were pleased with the telemedicine service, 71.9 0% were very satisfied (n = 62), 28.10% were very satisfied (n = 11), and 0% were dissatisfied (n = 0). CONCLUSIONS: Smartphone otoscopes telemedicine can decrease outpatient follow-up, reduce the risk of cross-infection, increase telemedicine accuracy, and improve patient satisfaction. It is worthy of clinical application in the COVID-19 era.

Fluorophore-Promoted Facile Deprotonation and Exocyclic Five-Membered Ring Cyclization for Selective and Dynamic Tracking of Labile Glyoxals.

The lack of effective chemical tools capable of dynamic tracking of labile glyoxal species (GOS) [e.g., methylglyoxal (MGO) and glyoxal (GO)] levels with high selectivity over other relevant electrophilic species, particularly, formaldehyde (FA) and nitric oxide (NO), has significantly hampered the understanding of their roles in a complex metabolic network and disease progressions. Herein, we report the rational design of the bioinspired 4-(2-guanidino)-1,8-naphthalimide fluorescent probes NAP-DCP-1 and NAP-DCP-3 from arginine-specific protein modifications. These probes undergo facile reversible fluorophore-promoted deprotonation-cyclization of a guanidium ion with labile GOS to form exocyclic five-membered dihydroxyimidazolidines. The probe NAP-DCP-1 can differentiate GOS levels in the serum of diabetic mice and patients from nondiabetic ones, which correlate very well with glucose levels, providing the GOS level as a potential new biomarker for diabetes diagnosis. Notably, the endoplasmic reticulum (ER)-targeting probe NAP-DCP-3 enabled the study of GOS perturbation in ER under various stress conditions and led to the discovery that formaldehyde (FA), either exogenously added or endogenously generated, could induce GOS level increases in ER. This finding reveals the previous unknown connection of FA with upregulated GOS levels and suggests that GOS is a key metabolite in bridging one-carbon metabolism with glycolysis and the downstream cell redox status. Moreover, the probes also showed potentials in separate quantification of MGO and GO via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and unexpected selectivity modulation for GO over MGO via two-photon excitation. It is expected that probes reported herein provide powerful tools to study GOS level modulations in complex biological networks and would facilitate GOS-associated basic research and discovery.

Steric and Electrostatic Control of the pH-Regulated Interconversion of Au16(SR)12 and Au18(SR)14 (SR: Deprotonated Captopril).

An understanding of the response of nanomaterials to specific environmental parameters is an essential prerequisite for their practical use, especially in living systems. Herein, we disclose the preparation of a water-soluble nanocluster Au16(SR)12 (SR denotes deprotonated captopril) and its characterization by a combination of theoretical (e.g., density functional theory calculations) and experimental (UV-vis, electrospray ionization mass spectrometry, etc.) methods. Interestingly, Au16(SR)12 was found to convert to Au18(SR)14 under acidic conditions, while the reverse conversion from Au18(SR)14 to Au16(SR)12 occurred upon the addition of base. A mechanistic investigation determined this pH regulation to originate from the distinct steric and electrostatic properties of these two clusters. This study is the first to report the susceptibility of Au18(SR)14 and Au16(SR)12 to pH, and the distinct pH stability unambiguously reveals the importance of size-tracking of nanomaterials in living systems for future clinical applications.

COVID-19 and anosmia: A review based on up-to-date knowledge.

The pandemic of Coronavirus Disease 2019 (COVID-19) has caused a vast disaster throughout the world. There is increasing evidence that olfactory dysfunction can present in COVID-19 patients. Anosmia can occur alone or can be accompanied by other symptoms of COVID-19, such as a dry cough. However, the pathogenic mechanism of olfactory dysfunction and its clinical characteristics in patients with COVID-19 remains unclear. Multiple cross-sectional studies have demonstrated that the incidence rate of olfactory dysfunction in COVID-19 patients varies from 33.9-68% with female dominance. Anosmia and dysgeusia are often comorbid in COVID-19 patients. Otolaryngologists should be mindful of the symptom of anosmia in outpatients so as not to delay the diagnosis of COVID-19. In this paper, we have reviewed the relevant knowledge based on up-to-date literature.

Videolaryngoscope-assisted coblation of epiglottic cysts.

PURPOSE: This study aims to investigate the safety and effectiveness of videolaryngoscope-assisted coblation of epiglottic cysts (VACECs) under general anesthesia. METHODS: Twenty-eight consecutive patients with epiglottic cysts (ECs), underwent VACECs in this prospective clinical series from January 2015 to March 2019. The pre-operative electronic flexible laryngoscopic or 70° rigid laryngeal endoscopic examination was carried out to assess the location and size of ECs. There was a periodical follow-up survey for all patients. RESULTS: A total 28 of patients were enrolled, including 12 men and 16 women, with an average age of 55 (range 24-78). The patient's medical history ranged from half a month to 2 years. The size of the cyst arranged from 0.8 to 1.5 cm. All patients were cured without pharyngeal or systemic complications. No tooth loss occurred in five patients (17.9%) with loose anterior teeth. Specimen pathology confirmed the diagnosis in all patients. No recurrence was found after more than half a year's follow-up. CONCLUSIONS: VACECs brings together the advantages of videolaryngoscope and coblation. It is a simple, safe and feasible procedure for patients with ECs and is worthy of clinical application.

Delivery of cell membrane impermeable peptides into living cells by using head-to-tail cyclized mitochondria-penetrating peptides.

A series of cyclic Arg-rich mitochondria-penetrating peptides were prepared with variation in the macrocycle size and the chirality of Arg residues. A cyclic heptapeptide was demonstrated to be an efficient mitochondria-specific delivery vector for delivering membrane impermeable peptides.

In Situ Lysosomal Cysteine-Specific Targeting and Imaging during Dexamethasone-Induced Apoptosis.

Herein we utilize the similar though divergent nucleophilic properties of cysteine, homocysteine, and glutathione to achieve the selective detection of cysteine under mildly acidic conditions. This enables the specific in situ detection of lysosomal cysteine. Employing time-dependent fluorescent imaging of probe-labeled A549 cells, we demonstrate that dexamethasone-induced apoptosis is not dependent on lysosomal cysteine. This methodology can thus produce useful information about pathogenesis associated with cysteine and lysosomes.

Two-Photon Fluorescent Probe for Monitoring Autophagy via Fluorescence Lifetime Imaging.

We reported the first lysosome targeted two-photon fluorescent probe (Lyso-NP) as a viscosity probe for monitoring autophagy. The fluorescence lifetime of Lyso-NP exhibited an excellent linear relationship with viscosity value ( R2 = 0.99, x = 0.39). Lyso-NP also showed the specific capability for imaging lysosomal viscosity under two-photon excitation at 860 nm along with good biocompatibility. More importantly, Lyso-NP could be used to monitor the autophagy process in living cells by quantitatively detecting lysosomal viscosity changes during the membrane fusion process via two-photon fluorescence lifetime imaging.

Dual-Site Fluorescent Probe for Visualizing the Metabolism of Cys in Living Cells.

Fluorescent probes, as noninvasive tools for visualizing the metabolism of biomolecules, hold great potential to explore their physiological and pathological processes. For cysteine (Cys), however, none of the reported fluorescent probes could image the metabolic processes in living cells. To achieve this goal, we developed a coumarin derivative based on rational design of the dual recognition sites for Cys and its metabolite, SO2. The probe displayed distinct two channels with turn-on fluorescent emission toward Cys and SO2, which were successfully applied for imaging both A549 cells and zebrafish. Further, with reversible fluorescent responses toward Cys, the probe could image the enzymatic conversion of Cys to SO2 in living A549 cells in a ratiometric manner. The present work reports the first probe to image the endogenous generated SO2 without incubation of the SO2 donors.

Reversible Ratiometric Fluorescent Probe for Sensing Bisulfate/H2O2 and Its Application in Zebrafish.

Herein, a novel near-infrared fluorescent probe for ratiometric detection of bisulfate was designed and developed based on a conjugation of naphthopyran-benzothiazolium system. The sensor showed excellent selectivity, high sensitivity and a rapid response toward bisulfite in aqueous solution. Upon the addition of HSO3-, the sensor displayed 37-fold (I520/I630) fluorescence intensity enhancement, accompanied by an apparent color change from violet to colorless, suggesting that the sensor can be used to detect HSO3- with "naked-eye". Notably, the addition product can be applied to the design of regenerative chemodosimeters based on the H2O2 promoted elimination of bisulfite and recovery of probe 1. Further cell and zebrafish imaging experiment demonstrated that the sensor could image the bisulfite/H2O2 redox cycle in biological system with ratiometric manners.