Multienzyme-Like Polyoxometalate-Based Single-Atom Enzymes for Cancer-Specific Therapy Through Acid-Triggered Nontoxicity-to-Toxicity Transition.

Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues. Under acid TME conditions, these nanospheres are degraded into smaller units of toxic Mn(II)-PW11; thus, initiating cancer cell-specific therapy. The released active units of Mn(II)-PW11 exhibit excellent multienzyme-like activities (including peroxidase (POD)-like, oxidase (OXD)-like, catalase (CAT)-like, and glutathione peroxidase (Gpx)-like activities) for the synergistic cancer therapy due to the stabilized high valence Mn species (MnIII/MnIV). As demonstrated by both intracellular evaluations and in vivo experiments, ROS is generated to cause damage to lysosome membranes, further facilitating acidification and impaired autophagy to enhance cancer therapy. This study provides a detailed investigation on the acid-triggered releasing of active units and the electron transfer in multienzyme-mimic-like therapy, further enlarging the application of POMs from catalytical engineering into cancer therapy.

Unusual presentation of PD-1 inhibitors in people living with HIV with advanced gastric cancer: Case report.

This paper seeks to determine the effect of combination anti-PD-1 and antiretroviral therapy (ART) on people living with HIV (PLWH) with advanced gastric cancer. In our case, a PLWH with recurrent locally advanced gastric cancer was treated with anti-PD-1 inhibitor and ART. A significant reduction in tumor lesions (as demonstrated by contrast-enhanced CT imaging) and a better quality of life were achieved following treatment. There have been limited studies on the treatment of PLWH with advanced gastric cancer. Chemotherapy is most often used, however, with unsatisfactory outcomes. to date, there have been no published reports on the use of PD-1 inhibitors in PLWH with advanced gastric cancer. Our report provides a valuable reference for future management of such patients.

Association between CT-based adipose variables, preoperative blood biochemical indicators and pathological T stage of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is corelated with tumor-associated material (TAM), coagulation system and adipocyte tissue, but the relationships between them have been inconsistent. Our study aimed to explore the cut-off intervals of variables that are non-linearly related to ccRCC pathological T stage for providing clues to understand these discrepancies, and to effectively preoperative risk stratification. Methods: This retrospective analysis included 218 ccRCC patients with a clear pathological T stage between January 1st, 2014, and November 30th, 2021. The patients were categorized into two cohorts based on their pathological T stage: low T stage (T1 and T2) and high T stage (T3 and T4). Abdominal and perirenal fat variables were measured based on preoperative CT images. Blood biochemical indexes from the last time before surgery were also collected. The generalized sum model was used to identify cut-off intervals for nonlinear variables. Results: In specific intervals, fibrinogen levels (FIB) (2.63-4.06 g/L) and platelet (PLT) counts (>200.34 × 109/L) were significantly positively correlated with T stage, while PLT counts (<200.34 × 109/L) were significantly negatively correlated with T stage. Additionally, tumor-associated material exhibited varying degrees of positive correlation with T stage at different cut-off intervals (cut-off value: 90.556 U/mL). Conclusion: Preoperative PLT, FIB and TAM are nonlinearly related to pathological T stage. This study is the first to provide specific cut-off intervals for preoperative variables that are nonlinearly related to ccRCC T stage. These intervals can aid in the risk stratification of ccRCC patients before surgery, allowing for developing a more personalized treatment planning.

Synergistically remodulating H+/Ca2+ gradients to induce mitochondrial depolarization for enhanced synergistic cancer therapy.

The remodulation of H+/Ca2+ gradients in the mitochondria matrix could be effective to induce mitochondria depolarization for the enhancement of cancer therapy. However, it is still challenged by H+ homeostasis, insufficient Ca2+, uncoordinated regulations, and inefficient loading/delivery strategies. Herein, a supramolecular DNA nanocomplex (Ca@DNA-MF) was prepared to synergistically remodulate H+/Ca2+ gradients for mitochondrial depolarization. Upon targeted functionalization and TME-triggered delivery, multiple reagents were released in cancer cells for synergistic three-channel mitochondrial depolarization: the gene reagent of siMCT4 blocked the LA metabolism to induce mitochondrial acidification by downregulating monocarboxylate transporter 4 (MCT4); released Ca2+ disrupted Ca2+ homeostasis to facilitate Ca2+-based mitochondrial depolarization; specifically, TME-activated glutathione (GSH) depletion facilitated efficient generation of hydroxyl radicals (˙OH), further enhancing the mitochondrial depolarization. The remodulation not only triggered apoptosis but also led to ferroptosis to generate abundant ROS for efficient LPO-based apoptosis, providing a synergistic strategy for enhanced synergistic cancer therapy.

Dietary chitosan moderates the growth rate, antioxidant activity, immunity, intestinal morphology and resistance against Aeromonas hydrophila of juvenile hybrid sturgeon (Acipenser baerii♀ × Acipenser schrenckii♂).

This study investigated the effects of dietary chitosan on growth, antioxidant, immunity, intestinal morphology and resistance against Aeromonas hydrophila of hybrid sturgeon (Acipenser baerii♀ × Acipenser schrenckii♂). Sturgeons (18.18 ± 0.08 g) were randomly divided into four groups, fed with chitosan-supplemented diets for 8 weeks and then infected with A. hydrophila. The results showed significant differences of body weight gain, specific growth rate and feed conversion ratio in sturgeon fed chitosan and control diets. The oral administration of chitosan significantly increased the acid phosphatase, alkaline phosphatase, lysozyme, myeloperoxidase, superoxide dismutase, glutathione peroxidase and catalase activities, as well as the complement 3 and 4 contents and disease resistance against A. hydrophila. Moreover, enhancement of muscular thickness and goblet cells in mid intestine and increase of muscular thickness and villus height in spiral valve were observed in the chitosan supplemented groups. In addition, dietary chitosan-supplemented diets mitigated the changes of antioxidant and immune activity induced by A. hydrophila challenge, as well as prevented fish from bacterial invasion. The optimal dose was 3.00 g chitosan/kg diet for hybrid sturgeon.

Biomineralization of DNA Nanoframeworks for Intracellular Delivery, On-Demand Diagnosis, and Synergistic Cancer Treatments.

DNA nanoframeworks, with great biological information and controlled framework structures, exhibit great potentials in biological applications. Their applications are normally limited by unstable structures susceptible to hydrolysis, depurination, depyrimidination, oxidation, alkylation, or nuclease degradations. Herein, to ensure the mechanical and chemical stabilities of DNA nanoframeworks for intracellular applications, biomineralization of multifunctional DNA nanoframeworks with a tetrahedral skeleton is employed. Via silicification, the S-S bond is simultaneously introduced to obtain the silica-armored DNA nanoframeworks (Si-DNA nanoframeworks), mechanically and chemically stabilized for efficient intracellular deliveries. This successfully prevents degradations and leakages of reagents loaded on Si-DNA nanoframeworks, including biomolecular siRNA and small DOX drugs. Furthermore, the nucleic acid strands of the nanoframeworks are labeled with FAM and the quencher, facilitating miRNA detection upon "turn-on" signals from hybridizations. Therefore, the nanoframeworks collapse via double responses of the silica coating (silica acidic dissolution and S-S reduction by GSH) in cancer cells, realizing on-demand reagent release for miRNA detection and synergistic treatments (by siRNA and DOX). Demonstrated by both in vivo and in vitro experiments, the biomineralization has stabilized DNA nanomaterials for biological applications.

Co-infections of Aeromonas veronii and Nocardia seriolae in largemouth bass (Micropterus salmoides).

Largemouth bass (Micropterus salmoides) is an important commercial fish species that is widely cultured throughout China. With the application of high-density culture, M. salmoides is usually infected by different pathogens in water. Particularly, co-infection with multiple pathogens was common, which has considerably outweighed the impact caused by single infections. In this research, two bacteria strains were isolated from diseased fish by incubating on brain heart infusion agar. According to the results of 16S rRNA and gyrB sequence, as well as the analysis of morphological, physiological and biochemical features, the isolated bacterial strains were finally identified as Aeromonas veronii and Nocardia seriolae, respectively. In addition, eight virulence genes related to pathogenicity including enterotoxin, lipase, elastase, quorum sensing, hemolysin and adhesion were identified in A. veronii isolate and eight virulence genes encoding mammalian cell entry family proteins, glyceraldehyde-3-phosphate dehydrogenase, mycolyltransferase, nitrate reductase subunits, and putative cytotoxin/hemolysin were detected in N. seriolae isolate. Drug sensitivity testing indicated that both A. veronii and N. seriolae isolates were susceptible to kanamycin, streptomycin, gentamycin, neomycin, doxycycline, tetracycline, ciprofloxacin and levofloxacin, and resistant to amikacin, cefpimizole, ampicillin, piperacillin, carbenicillin, oxacillin, rifampicin, trimethoprim, vancomycin, meropenem, imipenem and sulfisoxazole. Moreover, serious histopathological changes, such as typical granulomas with necrotic center, cell degeneration and necrosis, hemorrhage and inflammatory cell infiltration, were found in the naturally diseased fish. The LD50 of A. veronii and N. seriolae isolates were 7.94 × 105 CFU/g and 3.16 × 106 CFU/g fish weight, respectively. In addition, the coinfection of A. veronii and N. seriolae induce quick and higher mortality in comparison with those challenged by single bacteria. These results revealed that both A. veronii and N. seriolae participated in the disease outbreaks of the M. salmoides, and concurrent of those two bacteria synergistically exacerbate the disease severity.

Modular and hierarchical self-assembly of siRNAs into supramolecular nanomaterials for soft and homogeneous siRNA loading and precise and visualized intracellular delivery.

siRNA therapeutics are challenged by homogeneous and efficient loading, maintenance of biological activities, and precise, dynamic and monitorable site-release. Herein, supramolecular nanomaterials of WP5⊃G-siRNA were constructed by modular and hierarchical self-assembly of siRNA with guest (3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione derivative, G) and host (pillar[5]arene, WP5) molecules in the same system. Demonstrated by experiments and theoretical calculations, WP5⊃G-siRNA was constructed via comprehensive weak interactions including electrostatic, hydrophobic-hydrophilic, host-guest and π-π interactions. Therefore, siRNAs were efficiently loaded, maintaining good stability, bioactivities and biocompatibilities. At pH 6.8, G was protonated to give weak acidic-responsive "turn-on" fluorescent signals, which realized the precise location of cancer sites. This triggered a subsequent delivery and a dynamic release of siRNA in cancer cells under acidic conditions for the entire collapse of WP5⊃G-siRNA by the protonation of both WP5 and G. By both in vitro and in vivo experiments, precise and visualized delivery to cancer sites was achieved to exhibit effective tumour inhibition. This provided an efficient and soft strategy of siRNA therapies and expanded the application of supramolecular nanomaterials in diagnosis and treatment.

The Protective Effect of Kaempferol Against Ischemia/Reperfusion Injury Through Activating SIRT3 to Inhibit Oxidative Stress

Abstract Introduction: The objective of this study is to investigate the protective effect of kaempferol against ischemia/reperfusion (IR) injury and the underlying molecular mechanisms. Methods: H9C2 cells were pretreated with kaempferol for 24 hours and further insulted with IR injury. Cell vitality, reactive oxygen species (ROS) level, glutathione (GSH) level, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and sirtuin-3 (SIRT3), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) expressions were evaluated. Moreover, short interfering ribonucleic acid targeting SIRT3 was used to investigate the role of SIRT3 against IR mediated by kaempferol in vitro. IR mice models were also established to confirm the protective effects of kaempferol on IR in vivo. Results: After IR injury, H9C2 cells vitality was reduced, ROS levels, NADPH oxidase activity, and Bax expressions were increased, and GSH levels and Bcl2 expressions were decreased. After kaempferol pretreatment, the vitality of H9C2 cells was increased. The levels of ROS, NADPH oxidase activity, and Bax expression were decreased. In addition, levels of GSH and Bcl2 expression were enhanced. Furthermore, silencing SIRT3 attenuated the protective effect mediated by kaempferol, with increased ROS levels, NADPH oxidase activity, and Bax expression, along with reduced GSH level and Bcl2 expression. In vivo IR model showed that kaempferol could preserve IR-damaged cardiac function. Conclusion: Kaempferol has the capability of attenuating H9C2 cells IR injury through activating SIRT3 to inhibit oxidative stress.

Occurrence, source, and ecological risk assessment of organochlorine pesticides and polychlorinated biphenyls in the water-sediment system of Hangzhou Bay and East China Sea.

The pollution characteristics, potential sources, and potential ecological risk of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were investigated in the Hangzhou Bay (HZB) and East China Sea (ECS). Total OCPs concentration ranged from 2.62 to 102.07 ng/L and 4.41 to 75.79 µg/kg in the seawater and sediment samples, with PCBs concentration in the range of 0.40-51.75 ng/L and 0.80-45.54 µg/kg, respectively. The OCPs were positively correlated with nutrients, whereas PCBs presented a negative correlation. The newly imported dichlorodiphenyltrichloroethane (DDT) in HZB is mainly the mixing of technical DDT and dicofol sources. The PCB source composition is more likely related to the mixture of Kanechlor 300, 400, Aroclor 1016, 1242, and Aroclor 1248. Risk assessment results indicate that OCPs posed low risk in seawater. The potential risk of DDTs in the sediments is a cause of concern.

Subcutaneous pedicled propeller flap for reconstructing the large eyelid defect due to excision of malignancies or trauma.

Large eyelid defect after excision of malignancies or trauma is difficult to reconstruct due to special structure and function of the eyelid. In this study, we aimed to present the outcomes of subcutaneous pedicled propeller flap for reconstructing the large eyelid defect after excision of malignancies or trauma. A retrospective review of patients diagnosed with eyelid defect due to excision of malignancies or trauma, and undergoing subcutaneous pedicled propeller flap for reconstructing the large eyelid defect, was conducted at our hospital. The clinical data were collected and analyzed. A total of 15 patients were included in the cases series. Nine patients were diagnosed with basal cell carcinoma, 3 patients with epidermoid carcinoma, and 3 patients with trauma. All the defects were successfully covered with this designed flap. There was no flap necrosis in all the cases. No functional problems were observed in all of the cases. At long-term postoperative follow-up, the average score of patients' satisfaction was good. This subcutaneous pedicled propeller flap is a feasible alternative technique for reconstructing the large eyelid defect after excision of malignancies or trauma. This flap option could avoid the use of free flaps for large defect.

Ligand-of-Numb protein X1 controls the coxsackievirus B3-induced myocarditis via regulating the stability of coxsackievirus and adenovirus receptor.

Group B coxsackieviruses (CVBs) are the main cause of virus-induced myocarditis. CVBs use coxsackievirus and adenovirus receptor (CAR) for infection and targeting CAR has been shown to ameliorate CVBs-induced myocarditis. Ligand-of-Numb protein X1 (LNX1) is an E3 ubiquitin ligase that was shown to interact with CAR. However, the precise effect of LNX1 on CAR and the roles of LNX1 on CVBs-induced myocarditis remain unknown. In the present study, we generated mice deficient in LNX1 in the heart and evaluated the symptoms of myocarditis after CVB3 infection. We also monitored the expression and ubiquitination of CAR in LNX1-deficient cardiomyocytes after CVBs infection. We found that CVBs infection decreased CAR expression while promoted the expression of LNX1. Mice with deficiency of LNX1 in the heart had normal myocardial development while had deteriorated myocarditis symptoms after CVB3 infection. In LNX1-deficient cardiomyocytes, decreased ubiquitination of CAR and upregulation of CAR were observed after CVB3 infection. In summary, LNX1 controls CVB3-induced myocarditis by regulating the expression of CAR.

The Protective Effect of Kaempferol Against Ischemia/Reperfusion Injury Through Activating SIRT3 to Inhibit Oxidative Stress.

INTRODUCTION: The objective of this study is to investigate the protective effect of kaempferol against ischemia/reperfusion (IR) injury and the underlying molecular mechanisms. METHODS: H9C2 cells were pretreated with kaempferol for 24 hours and further insulted with IR injury. Cell vitality, reactive oxygen species (ROS) level, glutathione (GSH) level, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and sirtuin-3 (SIRT3), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) expressions were evaluated. Moreover, short interfering ribonucleic acid targeting SIRT3 was used to investigate the role of SIRT3 against IR mediated by kaempferol in vitro. IR mice models were also established to confirm the protective effects of kaempferol on IR in vivo. RESULTS: After IR injury, H9C2 cells vitality was reduced, ROS levels, NADPH oxidase activity, and Bax expressions were increased, and GSH levels and Bcl2 expressions were decreased. After kaempferol pretreatment, the vitality of H9C2 cells was increased. The levels of ROS, NADPH oxidase activity, and Bax expression were decreased. In addition, levels of GSH and Bcl2 expression were enhanced. Furthermore, silencing SIRT3 attenuated the protective effect mediated by kaempferol, with increased ROS levels, NADPH oxidase activity, and Bax expression, along with reduced GSH level and Bcl2 expression. In vivo IR model showed that kaempferol could preserve IR-damaged cardiac function. CONCLUSION: Kaempferol has the capability of attenuating H9C2 cells IR injury through activating SIRT3 to inhibit oxidative stress.

The diversity of the coordination bond generated a POSS-based fluorescent probe for the reversible detection of Cu(II), Fe(III) and amino acids.

In recent years, it has been found that Cu2+, Fe3+, and amino acids play an irreplaceable and subtle role in organisms and have attracted the considerable attention of many researchers. Therefore, it is vital to design visual indicators to reveal the relationships between metal ions and amino acids. However, there have been few reports on this vigorous subject. Fortunately, based on the different coordination effects between metal ions and boron groups, we have designed an accessible fluorescent probe (PSI-A). Borane was introduced as an ion-sensitive group to form a novel POSS-based fluorescent probe, which achieves fascinating performance, in situ dynamic multiple detection, excellent photostability, and enervative biological toxicity. PSI-A exhibited predominant selectivity and sensitivity to Cu2+/amino acids and Fe3+/amino acids sequence reactions in HepG2 cells and zebrafish. The fluorescence of PSI-A was quenched by Cu2+, which can be recovered by adding Asp, Ser, Arg, Ace or Trp. Additionally, the fluorescence of PSI-A quenched by Fe3+ can be restored after adding Asp. PSI-A is available to monitor Cu2+/amino acids and Fe3+/amino acids sequence reactions and can be repeated for at least three consecutive cycles without a fatigued performance. Therefore, this multifunctional fluorescent probe may have prospective application potentials in the biological field.

A POSS-assisted fluorescent probe for the rapid detection of HClO in mitochondria with a large emission wavelength in dual channels.

Hypochlorous acid (HClO) is closely related to many diseases and is an inevitable part of the physiological processes. It is significant to detect HClO in mitochondria for getting meaningful physiological and pathological information. However, adequate tools to detect HClO with emissions in two channels are rarely reported. To achieve this target, in this work, a "turn-off" visual and near infrared (NIR) fluorescent dual emission probe D6 based on polyhedral oligomeric silsesquioxanes (POSS) was successfully designed and synthesized. D6 showed high selectivity and sensitivity to HClO. Notably, the emission wavelength of D6 reached 820 nm due to the assistance of the POSS cage. In addition, bioimaging experiments clearly showed that probe D6 promoted the visualization of exogenous and endogenous HClO in living HepG2 cells and zebrafish models.

Study on the mechanism of photodynamic therapy mediated by 5-aminoketovalerate in human ovarian cancer cell line.

We aimed to investigate the mechanism and effect of photodynamic treatment mediated by 5-aminoketovalerate (5-ALA-PDT) on human ovarian cancer cells (OVCAR3 cells) and to provide a theoretical basis for the subsequent experimental step in vivo. Human ovarian cancer OVCAR3 cells were randomly divided into four groups: control group, laser irradiation alone group, photosensitizer alone group, and photodynamic treatment group. Alterations in cell morphology were observed with an inverted light microscope; cell viability was examined by CCK-8 assays. The ROS content and apoptosis rate were examined by flow cytometry analysis. Western blot was used to detect the expression of apoptosis-related proteins, such as caspase-3, Bax, and Bcl-2, and the expression of cleaved caspase-3 in live cells was detected by a cleaved caspase-3 assay kit. Inverted light microscopy showed alterations in cell morphology in different stages. Comparison with the three other groups indicated that tumor cell proliferation was significantly decreased in the photodynamic treatment group (P < 0.05). Flow cytometry analysis revealed that the content of ROS was higher in the photodynamic group than in the other three groups, and the apoptosis rate was higher in the photodynamic treatment group. The difference compared with the other three groups was statistically significant (P < 0.001). The western blot results indicated that the protein expression of Bcl-2 and caspase-3 was decreased in the photodynamic treatment group, and the protein expression level of Bax was increased (P < 0.05). The expression of cleaved caspase-3 was increased in the photodynamic treatment group compared with the other groups according to the data obtained with a microplate reader. Thus, our results demonstrated that the apoptosis and viability of OVCAR3 cells are altered in response to 5-ALA-PDT; however, no remarkable effects were observed in ovarian cancer cells treated with laser irradiation or photosensitizer alone. 5-ALA-PDT can significantly inhibit the growth of human ovarian cancer cells, and the mechanism of this effect is related to the tumor cell apoptosis mediated by the downregulation of Bcl-2 and caspase-3 and upregulation of Bax protein expression.

Plasma ß-Amyloid Levels Associated With Structural Integrity Based on Diffusion Tensor Imaging in Subjective Cognitive Decline: The SILCODE Study.

Background: Accumulating evidence has demonstrated that plasma ß-amyloid (Aß) levels are useful biomarkers to reflect brain amyloidosis and gray matter structure, but little is known about their correlation with subclinical white matter (WM) integrity in individuals at risk of Alzheimer's disease (AD). Here, we investigated the microstructural changes in WM between subjects with low and high plasma Aß levels among individuals with subjective cognitive decline (SCD). Methods: This study included 142 cognitively normal individuals with SCD who underwent a battery of neuropsychological tests, plasma Aß measurements, and diffusion tensor imaging (DTI) based on the Sino Longitudinal Study on Cognitive Decline (SILCODE). Using tract-based spatial statistics (TBSS), we compared fractional anisotropy (FA), and mean diffusivity (MD) in WM between subjects with low (N = 71) and high (N = 71) plasma Aß levels (cut-off: 761.45 pg/ml for Aß40 and 10.74 pg/ml for Aß42). Results: We observed significantly decreased FA and increased MD in the high Aß40 group compared to the low Aß40 group in various regions, including the body, the genu, and the splenium of the corpus callosum; the superior longitudinal fasciculus; the corona radiata; the thalamic radiation; the external and internal capsules; the inferior fronto-occipital fasciculus; and the sagittal stratum [p < 0.05, familywise error (FWE) corrected]. Average FA values were associated with poor performance on executive and memory assessments. No significant differences were found in either MD or FA between the low and high Aß42 groups. Conclusion: Our results suggest that a correlation exists between WM integrity and plasma Aß40 levels in individuals with SCD.

AIE-active polysiloxane-based fluorescent probe for identifying cancer cells by locating lipid drops.

Comparing with normal cells, Lipid droplets (LDs) of cancer cells show lower polarity and less quantity, which can be utilized as a marker for cancer diagnosis. However, the investigation of LDs in living cancer cells is restricted by the lack of effective molecular tools. Herein, we first reported a novel polysiloxane-based polymer fluorescent polar probe TR-1 with AIE properties, which realized the possibilities for locating LDs. It can aggregate in the LDs of cancer cells and show a stronger fluorescent signal to conduct cancer diagnosis. Moreover, the excellent photostability of TR-1 enable stable fluorescence to exhibit in cancer cells during effective time.

Extracellular vesicles as an emerging tool for the early detection of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a series of interacting pathophysiological cascades, including the aggregation of ß-amyloid plaques and the formation of neurofibrillary tangles derived from hyperphosphorylated tau proteins. AD is the cause of approximately 70 % of dementia, an irreversible and untreatable syndrome at its late stage. Hence, more efforts should be devoted to identifying at-risk or preclinical AD populations for early intervention and the improved design of drug trials. The exosome, a nanoscale subtype of extracellular vesicle that serves as a cell-to-cell communication messenger, is an emerging liquid biopsy tool for various diseases including AD. Recently, it has been discovered that brain-derived exosomes can flow through the blood-brain barrier to the peripheral blood, containing important protein and nucleic acid biomarkers that are associated with the pathogenesis and progression of AD. Other reports showed a strong involvement of exosomes in synaptic function, insulin resistance, and neuroinflammation, among others. Here, we summarize those studies and assess the value of exosomes as an emerging tool for the early detection of AD in conjunction with the current clinical diagnosis paradigm.

Novel fluorescent probe with a bridged Si-O-Si bond for the reversible detection of hypochlorous acid and biothiol amino acids in live cells and zebrafish.

Herein, we report the design of a novel fluorescent probe consisting of a naphthalimide fluorophore and a silicone small molecule for the reversible detection of hypochlorous acid and biothiol amino acids. The response mechanism of BSi-1 is based on the concept of the S-based oxidation/reduction. The probe was found to be suitable for imaging HOCl in HeLa, RAW 264.7 cells and zebrafish, demonstrating its utility in biological applications.