In Situ Symbiosis of Cerium Oxide Nanophase for Enhancing the Oxygen Electrocatalysis Performance of Single-Atom Fe─N─C Catalyst with Prolonged Stability for Zinc-Air Batteries.

The Fenton reaction, induced by the H2O2 formed during the oxygen reduction reaction (ORR) process leads to significant dissolution of Fe, resulting in unsatisfactory stability of the iron-nitrogen-doped carbon catalysts (Fe-NC). In this study, a strategy is proposed to improve the ORR catalytic activity while eliminating the effect of H2O2 by introducing CeO2 nanoparticles. Transmission electron microscopy and subsequent characterizations reveal that CeO2 nanoparticles are uniformly distributed on the carbon substrate, with atomically dispersed Fe single-atom catalysts (SACs) adjacent to them. CeO2@Fe-NC achieves a half-wave potential of 0.89 V and a limiting current density of 6.2 mA cm-2, which significantly outperforms Fe-NC and commercial Pt/C. CeO2@Fe-NC also shows a half-wave potential loss of only 1% after 10 000 CV cycles, which is better than that of Fe-NC (7%). Further, H2O2 elimination experiments show that the introduction of CeO2 significantly accelerate the decomposition of H2O2. In situ Raman spectroscopy results suggest that CeO2@Fe-NC significantly facilitates the formation of ORR intermediates compared with Fe-NC. The Zn-air batteries utilizing CeO2@Fe-NC cathodes exhibit satisfactory peak power density and open-circuit voltage. Furthermore, theoretical calculations show that the introduction of CeO2 enhances the ORR activity of Fe-NC SAC. This study provides insights for optimizing SAC-based electrocatalysts with high activity and stability.

Combination of deep learning and 2D CARS figures for identification of amyloid-ß plaques.

In vivo imaging and accurate identification of amyloid-ß (Aß) plaque are crucial in Alzheimer's disease (AD) research. In this work, we propose to combine the coherent anti-Stokes Raman scattering (CARS) microscopy, a powerful detection technology for providing Raman spectra and label-free imaging, with deep learning to distinguish Aß from non-Aß regions in AD mice brains in vivo. The 1D CARS spectra is firstly converted to 2D CARS figures by using two different methods: spectral recurrence plot (SRP) and spectral Gramian angular field (SGAF). This can provide more learnable information to the network, improving the classification precision. We then devise a cross-stage attention network (CSAN) that automatically learns the features of Aß plaques and non-Aß regions by taking advantage of the computational advances in deep learning. Our algorithm yields higher accuracy, precision, sensitivity and specificity than the results of conventional multivariate statistical analysis method and 1D CARS spectra combined with deep learning, demonstrating its competence in identifying Aß plaques. Last but not least, the CSAN framework requires no prior information on the imaging modality and may be applicable to other spectroscopy analytical fields.

The association between fatty liver index and onset of diabetes: secondary analysis of a population-based cohort study.

BACKGROUND: According to research, the fatty liver index (FLI) is associated with diabetes. However, few studies have been conducted to investigate the relationship between FLI and diabetes risk from various perspectives. This study comprehensively investigated the relationship between FLI and incident diabetes in a large Japanese population. METHODS: This retrospective cohort study included 14,280 participants from Murakami Memorial Hospital in Japan from 2004 to 2015. The independent and dependent variables are FLI and risk of type 2 diabetes mellitus (T2DM), respectively. To examine the link between FLI and incident T2DM, Cox proportional-hazards regression was employed. In addition, we performed a number of sensitivity studies to guarantee the validity of the results. Moreover, we conducted subgroup analyses. RESULTS: After adjusting covariates, the results showed that FLI was positively associated with the risk of T2DM (HR = 1.019, 95%CI: 1.012, 1.025). Additionally, the sensitivity analysis showed how reliable the outcomes were. And a stronger association between FLI and incident T2DM was observed in the regular exercisers (HR = 1.036, 95%CI: 1.019-1.053, P < 0.0001) and the population without ethanol consumption (HR = 1.028, 95%CI: 1.017-1.039, P < 0.0001). Besides, receiver operating characteristic (ROC) curve analysis showed that FLI was better than waist circumference, triglycerides, body mass index, and gamma-glutamyl transferase in predicting incident T2DM. CONCLUSION: FLI is positively associated with incident T2DM.

Extracorporeal Shock Wave Therapy Improves Nontraumatic Knee Contracture in a Rat Model.

BACKGROUND: Joint contractures occur frequently after trauma or immobilization, but few reliable treatments are available. Extracorporeal shock wave therapy (ESWT) is often used for various musculoskeletal conditions, but whether it is effective for treating joint contractures and the mechanisms through which it might work for that condition remain unclear. QUESTIONS/PURPOSES: Using a rat model, we asked, does ESWT (1) inhibit the progression of knee contracture, (2) ameliorate histopathologic joint changes, and (3) improve serum and myofascial fibrosis-related factors? We also asked, (4) what is the possible mechanism by which ESWT inhibits knee contracture? METHODS: Thirty-two male Sprague-Dawley rats (12 weeks old and weighing 300 to 400 g) were randomly separated into two groups: control group (eight rats) and noncontrol group (24) in the first week. Rats in the control group were kept free in cages for 4 weeks, and the right lower limbs of the rats in the noncontrol group were immobilized in plaster for 4 weeks. ROM was then measured for each rat with or without 4 weeks of immobilization. After ROM measurement, rats in the noncontrol group were randomly separated into three groups: immobilization group (eight rats), remobilization group (eight rats), and remobilization with ESWT group (eight rats) at Week 4. Knee contracture was induced in rats by fixing the right knee with a plaster cast as in a previous study. The plaster cast was removed after 4 weeks; knee contracture was established when passive ROM was decreased and dysfunction such as abnormal gait occurred. Subsequently, rats with a remobilized joint contracture were treated with or without ESWT for 15 days (on Days 5, 10, and 15). The therapeutic effect was examined using ROM, joint diameter (as an indication of swelling), histopathologic changes, and the levels of fibrosis-related extracellular matrix component factors (hyaluronic acid, serum procollagen peptide, and laminin). The effect of ESWT on fibrosis protein was also evaluated using immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blot. The expressions of factors in the TGF-ß/SMADs pathway were also determined using Western blot and qPCR. RESULTS: ESWT mitigated immobilization-induced knee contracture in rats by improving ROM (immobilization versus remobilization with ESWT: 53° ± 8° versus 32° ± 8° [95% confidence interval 13° to 30°]; p < 0.001) and joint swelling (immobilization versus remobilization with ESWT: 8 ± 0.8 cm versus 6 ± 0.3 cm [95% CI 0.4 to 2.2 cm]; p = 0.01). Histopathologic features of remission were alleviated after ESWT (immobilization versus remobilization with ESWT: thickness of the knee space: 0.2 ± 0.03 mm versus 0.6 ± 0.01 mm [95% CI -0.49 to -0.33 mm]; p < 0.001. On Masson staining, the positive expression area, which indicates collagen fiber deposition, was 24% ± 5% versus 9% ± 2% ([95% CI 10% to 21%]; p < 0.001). ESWT improved the serum fibrosis factors of hyaluronic acid, procollagen peptide, and laminin (immobilization versus remobilization with ESWT: hyaluronic acid: 412 ± 32 versus 326 ±15 ng/mL [95% CI 29 to 144 ng/mL]; p = 0.003; serum procollagen peptide: 19 ± 1 versus 12 ±1 ng/mL [95% CI 3 to 11 ng/mL]; p < 0.001; laminin: 624 ± 78 versus 468 ±9 ng/mL [95% CI 81 to 231 ng/mL]; p = 0.006) and myofascial factors of α-SMA and Type I collagen associated with immobilization-induced contractures. CONCLUSION: The findings suggest that ESWT improved joint contracture by inhibiting the TGF-ß1/SMADs signaling pathway in rats. CLINICAL RELEVANCE: This work suggests ESWT may be worth exploring in preliminary research in humans to determine whether it may be a treatment option for patients with nontraumatic knee contractures. If the mechanism of ESWT can be confirmed in humans, ESWT might be a therapy for diseases involved in the TGF-ß1/SMADs signaling pathway, such as hypertroic scarring and scleroderma.

Dynamic Volumetric Imaging of Mouse Cerebral Blood Vessels In Vivo with an Ultralong Anti-Diffracting Beam.

Volumetric imaging of a mouse brain in vivo with one-photon and two-photon ultralong anti-diffracting (UAD) beam illumination was performed. The three-dimensional (3D) structure of blood vessels in the mouse brain were mapped to a two-dimensional (2D) image. The speed of volumetric imaging was significantly improved due to the long focal length of the UAD beam. Comparing one-photon and two-photon UAD beam volumetric imaging, we found that the imaging depth of two-photon volumetric imaging (80 µm) is better than that of one-photon volumetric imaging (60 µm), and the signal-to-background ratio (SBR) of two-photon volumetric imaging is two times that of one-photon volumetric imaging. Therefore, we used two-photon UAD volumetric imaging to perform dynamic volumetric imaging of mouse brain blood vessels in vivo, and obtained the blood flow velocity.

Rapid identification of rice species by laser-induced breakdown spectroscopy combined with pattern recognition.

Laser-induced breakdown spectroscopy (LIBS) combined with pattern recognition was proposed to discriminate rice species. LIBS spectra in the range of 210-480 nm wavelength from 11 different rice species were collected and preprocessed. Principal component analysis was applied to extract the characteristic variables from LIBS spectral data. Three pattern recognition methods, discriminant analysis, radial basis function neural network, and multi-layer perceptron neural network (MLP) were performed to compare the precision in identifying rice species. The results showed that the performance of the MLP model was better. The average identification rate of rice species reached 100% and 97.9% in the training and test sets, respectively, with MLP. The highest and lowest percentages for correct identification were 100% for early indica rice, Huai rice 5, Yan japonica 6, Lian japonica 8, Xuhan 1, Lvhan 1, Sheng rice 16, Yang japonica 687, and Fenghan 30, and 77.8% for Wuyu japonica rice in test sets. The overall results demonstrate that LIBS combined with MLP could be utilized to rapidly discriminate rice species.

Temperature Difference Triggering Controlled Growth of All-Inorganic Perovskite Nanowire Arrays in Air.

All-inorganic perovskites have attracted increasing worldwide interest due to its significantly improved stability in atmospheric environment compared to organic-inorganic hybrid perovskites, which renders it infinitely applicable in many fields such as electronics, optoelectronics, and energy storage. However, all-inorganic perovskites have to confront the challenges from fabrication before their wide utilization in the aforementioned applications. Liquid-phase synthesis holds the advantage of mass production and easy modulation of composition but with the deficiencies of relatively low crystallinity and disordered products. Interestingly, gas-phase growth has complementary characteristics compared to the liquid-phase method. In this work, it is proposed that a novel temperature difference triggers growth strategy to integrate the merits of the liquid- and gas-phase methods, and the feasibility of this strategy via a simple lab-use hot plate is demonstrated. High quality all-inorganic perovskites, cesium lead halide (CsPbX3 ) nanowire arrays, can be epitaxially grown as in a gas-phase method, but at the same time, the composition of products can be easily modulated by predesigning the recipe of precursors as in the liquid-phase method on a large scale. Notably, the as-fabricated CsPbX3 perovskite nanowire arrays demonstrate excellent stability and good optoelectronic properties in air. It is believed that this novel strategy can strikingly prompt the development of perovskites fabrication and applications in future.

Identification of Huanglongbing-infected navel oranges based on laser-induced breakdown spectroscopy combined with different chemometric methods.

In order to realize rapid identification of Gannan navel oranges infected by Huanglongbing (HLB), a full optical diagnostic method of laser-induced breakdown spectroscopy (LIBS) was proposed. All navel oranges were collected from Ganzhou, Jiangxi, China, and samples contain healthy and HLB-infected navel oranges. The LIBS spectra of the plasma plume were collected directly from the epidermis of these navel oranges. The navel orange LIBS spectra in the wavelength range of 200-1050 nm were pretreated with smoothing and multiple scatter correction; on the basis of 10×10-fold cross validation, a random forest (RF) model based on continuous wavelet transform (CWT) and principal component analysis (PCA) were analyzed to identify the navel orange of HLB. The results showed that the PCA-RF and CWT-RF models coupled with suitable methods in preprocessing data can identify HLB-infected navel oranges. The average accuracy obtained from the CWT-RF model was 96.86% in the training set and 97.45% in the test set; the average accuracy by the PCA-RF model was 97.64% in the training set and 97.89% in the test set. The overall results demonstrate that LIBS combined with CWT-RF or PCA-RF, as a valuable analytical tool, could be used for HLB-infected navel orange identification.

Combined immunochemotherapy achieving targeted co-delivery of chlorogenic acid and doxorubicin by sialic acid-modified liposomes enhances anti-cancer efficacy.

Malignant melanoma is a high-grade aggressive skin tumor with an increasing incidence and mortality rates worldwide. Chemotherapeutic drugs such as doxorubicin have limited efficacy against melanoma due to their poor sensitivity, severe side effects, and drug resistance. Recent studies have shown that combinations of immunotherapy and chemotherapy have a synergistic effect in enhancing the anti-tumor effect. Here, we have developed liposomes co-loaded with chlorogenic acid (CA) and doxorubicin (DOX), modified with sialic acid-octadecylamine conjugate (SA-ODA), designated CA-DOX-SAL, that facilitate drug delivery by recognizing Siglec-1 receptor on TAMs. The physicochemical studies revealed the particle size and zeta potential of CA-DOX-SAL as 128.3 ± 0.8 nm and - 4.33 ± 0.50 mV, respectively. In vitro, CA-DOX-SAL demonstrated robust cellular uptake through SA receptor-mediated tumor-associated macrophages (TAM) targeting and exerted greater cytotoxicity on tumor cells. In vivo, targeted liposomes were found to accumulate in the tumor area, leading to an improvement in anti-tumor efficacy. In addition, CA-DOX-SAL effectively inhibited B16F10 melanoma tumor growth by stimulating the transition from tumor-promoting M2-type to anti-tumor M1-type and directly killing tumor cells. Overall, the co-delivery of immunomodulatory CA and chemotherapeutic DOX presents a promising therapeutic strategy to enhance clinical outcomes in the treatment of melanoma.

Degradation of organic pollutants by the Cl-/PMS process.

The viewpoints on whether high concentrations of chloride ion (Cl-) promote or inhibit the oxidation activity of activated persulfates are still inconclusive. Furthermore, the degradation of organic pollutants by the persulfates in the presence of high Cl- concentrations without any activation medium has not yet been studied. In this work, the efficiency and mechanism of degradation of organic pollutants such as carbamazepine (CBZ), sulfadiazine (SDZ), and phenol (PN) by Cl--activated PMS (denoted as Cl-/PMS) were investigated. Results showed that Cl- could effectively activate PMS for the complete removal of CBZ, SDZ, and PN with reaction kinetic constants of 0.4516 min-1, 0.01753 min-1, and 0.06805 min-1, respectively. Parameters such as PMS dose, Cl- concentration, solution pH, and initial concentrations of organic pollutants that affect the degradation efficiencies of the Cl-/PMS process were optimized. Unlike conventional activated persulfates, it was confirmed that the free chlorine was the main active species in the Cl-/PMS process. Finally, the degradation by-products of CBZ and SDZ as well as their toxicity were detected, and a possible degradation pathway for CBZ and SDZ was proposed. Though higher toxic chlorinated by-products were generated, the Cl-/PMS process was still an efficient oxidation method for the removal of organic pollutants in aqueous solutions which contain high concentrations of Cl-.

A real-world disproportionality analysis of semaglutide: Post-marketing pharmacovigilance data.

AIM/INTRODUCTION: The recent adverse reactions associated with semaglutide have led the Food and Drug Administration (FDA) to issue a "black box warning", and it is necessary to analyze all reports of adverse reactions to improve the safety of its clinical use. MATERIALS AND METHODS: Statistical analyses and signal mining were performed by obtaining the adverse event reports related to semaglutide in the FAERS database from the first quarter of 2018 to the fourth quarter of 2023. We used disproportionality and Bayesian analysis to examine clinical and demographic attributes, trends reported quarterly, and contrasts between two distinct indications (obesity and type 2 diabetes). RESULTS: We found 10 unexpected adverse signals related to "pancreatic cancer", "intestinal obstruction", "cholecystitis", and "polycystic ovary" and both the two different indications had the same serious adverse reaction events occurring. CONCLUSIONS: This study identified many unexpected signals of serious adverse reactions, suggesting the importance of continuous post-marketing surveillance of semaglutide to understand its potential risks.

Cytochrome P450 CYP736A12 is crucial for Trichoderma asperellum-induced alleviation of phoxim phytotoxicity and reduction of pesticide residue in tomato roots.

Trichoderma can enhance the metabolism of organophosphate pesticides in plants, but the mechanism is unclear. Here, we performed high-throughput transcriptome sequencing of roots upon Trichoderma asperellum (TM) inoculation and phoxim (P) application in tomato (Solanum lycopersicum L.). A total of 4059 differentially expressed genes (DEGs) were obtained, including 2110 up-regulated and 1949 down-regulated DEGs in P vs TM+P. COG and KOG analysis indicated that DEGs were mainly enriched in signal transduction mechanisms. We then focused on the pesticide detoxification pathway and screened out cytochrome P450 CYP736A12 as a putative gene for functional analysis. We suppressed the expression of CYP736A12 in tomato plants by virus-induced gene silencing and analyzed tissue-specific phoxim residues, oxidative stress markers, glutathione pool, GST activity and related gene expression. Silencing CYP736A12 significantly increased phoxim residue and induced oxidative stress in tomato plants, by attenuating the TM-induced increased activity of antioxidant and detoxification enzymes, redox homeostasis and transcripts of detoxification genes including CYP724B2, GSH1, GSH2, GR, GPX, GST1, GST2, GST3, and ABC. The study revealed a critical mechanism by which TM promotes the metabolism of phoxim in tomato roots, which can be useful for further understanding the Trichoderma-induced xenobiotic detoxification and improving food safety.

Exploring the effect of photobiomodulation and gamma visual stimulation induced by 808 nm and visible LED in Alzheimer's disease mouse model.

Although photobiomodulation (PBM) and gamma visual stimulatqion (GVS) have been overwhelmingly explored in the recent time as a possible light stimulation (LS) means of Alzheimer's disease (AD) therapy, their effects have not been assessed at once. In our research, the AD mouse model was stimulated using light with various parameters [continuous wave (PBM) or 40 Hz pulsed visible LED (GVS) or 40 Hz pulsed 808 nm LED (PBM and GVS treatment)]]. The brain slices collected from the LS treated AD model mice were evaluated using (i) fluorescence microscopy to image thioflavine-S labeled amy-loid-ß (Aß) plaques (the main hallmark of AD), or (ii) two-photon excited fluorescence (TPEF) imaging of unlabeled Aß plaques, showing that the amount of Aß plaques was reduced after LS treatment. The imaging results correlated well with the results of Morris water maze (MWM) test, which demonstrated that the spatial learning and memory abilities of LS treated mice were noticeably higher than those of untreated mice. The LS effect was also assessed by in vivo nonlinear optical imaging, revealing that the cerebral amyloid angiopathy decreased spe-cifically as a result of 40 Hz pulsed 808 nm irradiation, on the contrary, the angiopathy reversed after visible 40 Hz pulsed light treatment. The obtained results provide useful reference for further optimization of the LS (PBM or GVS) parameters to achieve efficient phototherapy of AD.

Adsorption film with sub-milli-interface morphologies via direct ink writing for indoor formaldehyde removal.

In-situ thermally regenerated flexible adsorption films are superior for long-term purification of indoor low-concentration volatile organic compounds (VOCs). To further improve the adsorption kinetics of the films, the surface morphology of adsorption films was suggested in hierarchical channel structure. However, such structure is far from practical applications because of its complicated fabrication method and limited flexibility. In this study, we proposed a convenient and fast method named direct ink writing (DIW) based 3D printing to fabricate flexible adsorption films. Inks were prepared to have appropriate rheological properties and good printability. Three types of adsorption film (flat, straight finned, and trough-like finned) were constructed on flexible polyimide circuit substrates by DIW. We utilized the printed adsorption films for indoor level (1 ppm) formaldehyde removal. The trough-like finned film achieved the best performance among the three printed films, showing a 275% longer penetration time and 252% larger effective adsorption capacity than the flat film. By conducting a 7-cycle adsorption-desorption experiment (more than 12 h), we verified that the films' adsorption performance could effectively recover via in-situ heating. This work could dance around the complicated coating process, increase the structural flexibility and reduce the adsorbent interfacial modification cost.

Recent progress in the applications of gold-based nanoparticles towards tumor-targeted imaging and therapy.

Cancer death rate remains high all over the world, scientists are paying increasing attention to meet the requirements for precise diagnosis and therapy. Therefore, early diagnosis and active treatment can effectively improve the five-year survival rate of patients. In recent years, gold-based nanomaterials have received increasing attention in medical fields due to their excellent biocompatibility, low toxicity and unique properties. In addition, because of the inherent nature of gold nanomaterials including for computed tomography (CT), fluorescence/optical imaging (FI/OI), surface enhanced Raman spectroscopy imaging (SERS), photoacoustic imaging (PAI) and photothermal therapy (PTT), various gold nanomaterials were developed as theranostic nanoplatforms. In this review, we summarized the latest developments of nanomaterials in imaging and combined therapy, and the prospects for the future application of gold-based theranostic nanoplatforms were also proposed.

Synergistic photobiomodulation with 808-nm and 1064-nm lasers to reduce the ß-amyloid neurotoxicity in the in vitro Alzheimer's disease models.

Background: In Alzheimer's disease (AD), the deposition of ß-amyloid (Aß) plaques is closely associated with the neuronal apoptosis and activation of microglia, which may result in the functional impairment of neurons through pro-inflammation and over-pruning of the neurons. Photobiomodulation (PBM) is a non-invasive therapeutic approach without any conspicuous side effect, which has shown promising attributes in the treatment of chronic brain diseases such as AD by reducing the Aß burden. However, neither the optimal parameters for PBM treatment nor its exact role in modulating the microglial functions/activities has been conclusively established yet. Methods: An inflammatory stimulation model of Alzheimer's disease (AD) was set up by activating microglia and neuroblastoma with fibrosis ß-amyloid (fAß) in a transwell insert system. SH-SY5Y neuroblastoma cells and BV2 microglial cells were irradiated with the 808- and 1,064-nm lasers, respectively (a power density of 50 mW/cm2 and a dose of 10 J/cm2) to study the PBM activity. The amount of labeled fAß phagocytosed by microglia was considered to assess the microglial phagocytosis. A PBM-induced neuroprotective study was conducted with the AD model under different laser parameters to realize the optimal condition. Microglial phenotype, microglial secretions of the pro-inflammatory and anti-inflammatory factors, and the intracellular Ca2+ levels in microglia were studied in detail to understand the structural and functional changes occurring in the microglial cells of AD model upon PBM treatment. Conclusion: A synergistic PBM effect (with the 808- and 1,064-nm lasers) effectively inhibited the fAß-induced neurotoxicity of neuroblastoma by promoting the viability of neuroblastoma and regulating the intracellular Ca2+ levels of microglia. Moreover, the downregulation of Ca2+ led to microglial polarization with an M2 phenotype, which promotes the fAß phagocytosis, and resulted in the upregulated expression of anti-inflammatory factors and downregulated expression of inflammatory factors.

A new HClO-activated "turn-off" mitochondria-targetable NIR fluorescent probe for imaging of osteoarthritis in vivo.

Hypochlorous acid (HClO) as a biomarker of inflammation has been implicated in redox signaling and combating microbial infection. Therefore, it is of great significance to develop an efficient method for detection and analysis of HClO in osteoarthritis. Herein, a new"turn-off" mitochondria-targetable NIR fluorescent probe, NIR-ClO, was reported for specific analysis and imaging of osteoarthritis response-related HOCl levels in vitro and in vivo. In the presence of HClO, due to the specific HOCl-triggered C = C bond cleavage reaction, NIR-ClO obtained a high sensitive and selective fluorescence "On-Off" response toward HClO with a good limit of detection(LOD) as low as 28.3 nM, and showed a fast response time (<60 s) , which allow it to be used for detection of HClO under a simulated physiological condition. In addition, NIR-ClO was successfully used to imaging of HClO in living RAW264.7 cells and osteoarthritis model rat. The results suggest that NIR-ClO is a robust tool for future studies on diagnosis osteoarthritis.

Long-Term Repeatable In Vivo Monitoring of Amyloid-ß Plaques and Vessels in Alzheimer's Disease Mouse Model with Combined TPEF/CARS Microscopy.

Long-term, repeatable monitoring of the appearance and progress of Alzheimer's disease (AD) in real time can be extremely beneficial to acquire highly reliable diagnostic insights, which is crucial for devising apt strategies towards effective AD treatment. Herein, we present an optimized innovative cranial window imaging method for the long-term repeatable imaging of amyloid-ß (Aß) plaques and vessels in an AD mouse model. Basically, two-photon excitation fluorescence (TPEF) microscopy was used to monitor the fluorescently labeled Aß plaques, whereas the label-free blood vessels were studied using coherent anti-Stokes Raman scattering (CARS) microscopy in the live in vivo AD mouse model. It was possible to clearly observe the Aß deposition and vascular structure in the target cortex localization for 31 weeks in the AD mouse model using this method. The combined TPEF/CARS imaging studies were also instrumental in realizing the relationship between the tendency of Aß deposition and ageing. Essentially, the progression of cerebral amyloid angiopathy (CAA) in the AD mouse model was quantitatively characterized, which revealed that the proportion Aß deposition in the unit vessel can increase from 13.63% to 28.80% upon increasing the age of mice from 8 months old to 14 months old. The proposed imaging method provided an efficient, safe, repeatable platform with simple target localization aptitude towards monitoring the brain tissues, which is an integral part of studying any brain-related physiological or disease conditions to extract crucial structural and functional information.

Optical Imaging of Beta-Amyloid Plaques in Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial, irreversible, and incurable neurodegenerative disease. The main pathological feature of AD is the deposition of misfolded ß-amyloid protein (Aß) plaques in the brain. The abnormal accumulation of Aß plaques leads to the loss of some neuron functions, further causing the neuron entanglement and the corresponding functional damage, which has a great impact on memory and cognitive functions. Hence, studying the accumulation mechanism of Aß in the brain and its effect on other tissues is of great significance for the early diagnosis of AD. The current clinical studies of Aß accumulation mainly rely on medical imaging techniques, which have some deficiencies in sensitivity and specificity. Optical imaging has recently become a research hotspot in the medical field and clinical applications, manifesting noninvasiveness, high sensitivity, absence of ionizing radiation, high contrast, and spatial resolution. Moreover, it is now emerging as a promising tool for the diagnosis and study of Aß buildup. This review focuses on the application of the optical imaging technique for the determination of Aß plaques in AD research. In addition, recent advances and key operational applications are discussed.

Distinguishing Amyloid ß-Protein in a Mouse Model of Alzheimer's Disease by Label-Free Vibrational Imaging.

Due to the increase in the average age of humans, Alzheimer's disease (AD) has become one of the disorders with the highest incidence worldwide. Abnormal amyloid ß protein (Aß) accumulation is believed to be the most common cause of AD. Therefore, distinguishing the lesion areas can provide clues for AD diagnosis. Here, we present an optical spectroscopy and imaging approach based on coherent anti-Stokes Raman scattering (CARS). Label-free vibrational imaging of Aß in a mouse model of AD was performed to distinguish the lesion areas by studying the spectra of regions with and without Aß plaques. Raman spectra in Aß and non-Aß regions exhibited a specific difference in the intensity ratio of the wave peaks detected at 2850 and 2930 cm-1. In the non-Aß region, the ratio of the peak intensity at 2850 cm-1 to that at 2930 cm-1 was approximately 1, whereas that in the Aß region was 0.8. This label-free vibrational imaging may provide a new method for the clinical diagnosis and basic research of AD.