Medulloblastomas Initiated by Homologous Recombination Defects in Mice.

Germline mutations of homologous-recombination (HR) genes are among the top contributors to medulloblastomas. A significant portion of human medulloblastomas exhibit genomic signatures of HR defects. Whether ablation of Brca2 and Palb2, and their related Brca1 and Bccip genes, in the mouse brain can differentially initiate medulloblastomas was explored here. Conditional knockout mouse models of these HR genes and a conditional knockdown of Bccip (shBccip-KD) were established. Deletion of any of these genes led to microcephaly and neurologic defects, with Brca1- and Bccip- producing the worst defects. Trp53 co-deletion significantly rescued the microcephaly with Brca1, Palb2, and Brca2 deficiency but exhibited limited impact on Bccip- mice. For the first time, inactivation of either Brca1 or Palb2 with Trp53 was found to induce medulloblastomas. Despite shBccip-CKD being highly penetrative, Bccip/Trp53 deletions failed to induce medulloblastomas. The tumors displayed diverse immunohistochemical features and chromosome copy number variation. Although there were widespread up-regulations of cell proliferative pathways, most of the tumors expressed biomarkers of the sonic hedgehog subgroup. The medulloblastomas developed from Brca1-, Palb2-, and Brca2- mice were highly sensitive to a poly (ADP-ribose) polymerase inhibitor but not the ones from shBccip-CKD mice. These models recapitulate the spontaneous medulloblastoma development with high penetrance and a narrow time window, providing ideal platforms to test therapeutic agents with the ability to differentiate HR-defective and HR-proficient tumors.

Disrupted BRCA1-PALB2 interaction induces tumor immunosuppression and T-lymphocyte infiltration in HCC through cGAS-STING pathway.

BACKGROUND AND AIMS: BRCA1 (BRCA1 DNA repair associated) and PALB2 (partner and localizer of BRCA2) interact with each other to promote homologous recombination and DNA double-strand breaks repair. The disruption of this interaction has been reported to play a role in tumorigenesis. However, its precise function in HCC remains poorly understood. APPROACH AND RESULTS: We demonstrated that mice with disrupted BRCA1-PALB2 interaction were more susceptible to HCC than wild-type mice. HCC tumors arising from these mice showed plenty of T-lymphocyte infiltration and a better response to programmed cell death 1 (PD-1) antibody treatment. Mechanistically, disruption of the BRCA1-PALB2 interaction causes persistent high level of DNA damage in HCC cells, leading to activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in both malignant hepatocytes and M1 macrophages in the tumor microenvironment. The activated cGAS-STING pathway induces programmed cell death 1 ligand 1 expression via the STING-interferon regulatory factor 3 (IRF3)-signal transducer and activator of transcription 1 pathway, causing immunosuppression to facilitate tumorigenesis and tumor progression. Meanwhile, M1 macrophages with an activated cGAS-STING pathway could recruit T lymphocytes through the STING-IRF3 pathway, leading to T-lymphocyte infiltration in tumors. After normalizing immune responses by PD-1 antibody treatment, the infiltrating T lymphocytes attack tumor cells rapidly and effectively. CONCLUSIONS: This study reveals that persistent DNA damage caused by a defective BRCA pathway induces tumor immunosuppression and T-lymphocyte infiltration in HCC through the cGAS-STING pathway, providing insight into tumor immune microenvironment remodeling that may help improve HCC response to PD-1 antibody treatment.

Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China.

BACKGROUND: Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. METHODS: This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015-2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3-6 was assessed at 3 and 12 months. Multivariate logistic regression was used. RESULTS: Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53-3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38-0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). CONCLUSIONS: There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT02470624).

Transcranial direct current stimulation for upper extremity motor dysfunction in poststroke patients: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of transcranial direct current stimulation in poststroke patients with upper extremity motor dysfunction using a systematic review and meta-analysis. DATA SOURCES: We searched the Web of Science, Cochrane Library, EMBASE, and PubMed for randomized controlled trials investigating the effects of both active and sham stimulation up until January 27, 2024. REVIEW METHODS: Efficacy, including the upper extremity Fugl-Meyer Assessment, Action Research Arm Test, Barthel Index, and safety, were assessed. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool and the Physiotherapy Evidence Database Scale. Meta-analysis was performed using the RevMan 5.4 software. RESULTS: Forty-four studies with 1555 participants were included. Transcranial direct current stimulation proved effective in improving upper extremity motor function (standardized mean difference = 0.22, 95% confidence interval: 0.12-0.32, P < 0.001) and Barthel Index (mean difference = 4.65, 95% confidence interval: 2.82-6.49, P < 0.001). Subgroup analysis revealed the highest transcranial direct current stimulation efficacy in patients with subacute stroke. Both anodal and cathodal stimulation were effective against upper extremity motor dysfunction. C3/C4 was the most effective stimulus target. Optimal stimulation parameters included stimulus current densities <0.057 mA/cm2 for 20-30 min and <30 sessions. Adverse effects and dropouts during follow-up showed that transcranial direct current stimulation is safe and feasible. CONCLUSIONS: Our findings suggest that both anodal and cathodal stimulation were significantly effective in subacute stroke patients, particularly when preceding other treatments and when C3/C4 is targeted.

PL-ReliefTMplus Alleviates Atopic Dermatitis and Regulates Inflammatory Responses via Inhibiting NF-κB Signaling Pathway.

BACKGROUND: Atopic dermatitis (AD) has various detrimental effects on individuals with limited drug cure rates which necessitate the development of new treatment methods. PL-ReliefTMplus (PLR) is composed of SupraOlive, Crocus Sativus extracts and Citrus reticulata extracts. The effect of PLR on AD remains to be explored. METHODS: 2,4-dinitrofluorobenzene-induced AD model mice were involved and the histopathology of the skin lesions was observed along with the levels of inflammatory chemokines levels were measured. To further validate the molecular mechanism of PLR, RNA-seq was performed in HaCaT cells. Western blotting and immunofluorescence were performed to investigate NF-κB signaling pathways response in AD. RESULTS: Due to PLR treatment, the thickening of the epidermis and dermis was inhibited and the number of eosinophils, mast cells, and CD4+ T cells in the skin lesion was decreased. In addition, the levels of inflammatory cytokines were decreased in dorsal skin tissues and LPS-stimulated HaCat cells. Furthermore, KEGG pathway analysis suggested that most identified downstream biological functions were associated with inflammatory response. PLR inhibited NF-κB signaling in AD mice and HaCaT cells. CONCLUSIONS: These results indicate that PLR is a potent therapeutic agent for attenuating symptoms of AD.

Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression.

Increased lipid synthesis is a key characteristic of many cancers that is critical for cancer progression. ATP-citrate lyase (ACLY), a key enzyme for lipid synthesis, is frequently overexpressed or activated in cancer to promote lipid synthesis and tumor progression. Cullin3 (CUL3), a core protein for the CUL3-RING ubiquitin ligase complex, has been reported to be a tumor suppressor and frequently down-regulated in lung cancer. Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. Through negative regulation of ACLY, CUL3 inhibits lipid synthesis, cell proliferation, and xenograft tumor growth of lung cancer cells. Furthermore, ACLY inhibitor SB-204990 greatly abolishes the promoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth. Importantly, low CUL3 expression is associated with high ACLY expression and poor prognosis in human lung cancer. In summary, our results identify CUL3-KLHL25 ubiquitin ligase as a novel negative regulator for ACLY and lipid synthesis and demonstrate that decreased CUL3 expression is an important mechanism for increased ACLY expression and lipid synthesis in lung cancer. These results also reveal that negative regulation of ACLY and lipid synthesis is a novel and critical mechanism for CUL3 in tumor suppression.

From teeth to brain: dental caries causally affects the cortical thickness of the banks of the superior temporal sulcus.

OBJECTIVES: Dental caries is one of the most prevalent oral diseases and causes of tooth loss. Cross-sectional studies observed epidemiological associations between dental caries and brain degeneration disorders, while it is unknown whether dental caries causally affect the cerebral structures. This study tested whether genetically proxied DMFS (the sum of Decayed, Missing, and Filled tooth Surfaces) causally impacts the brain cortical structure using Mendelian randomization (MR). METHODS: The summary-level GWAS meta-analysis data from the GLIDE consortium were used for DMFS, including 26,792 participants. ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) consortium GWAS summary data of 51,665 patients were used for brain structure. This study estimated the causal effects of DMFS on the surface area (SA) and thickness (TH) of the global cortex and functional cortical regions accessed by magnetic resonance imaging (MRI). Inverse-variance weighted (IVW) was used as the primary estimate, the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy. RESULTS: Genetically proxied DMFS decreases the TH of the banks of the superior temporal sulcus (BANSSTS) with or without global weighted (weighted, ß = - 0.0277 mm, 95% CI: - 0.0470 mm to - 0.0085 mm, P = 0.0047; unweighted, ß = - 0.0311 mm, 95% CI: - 0.0609 mm to - 0.0012 mm, P = 0.0412). The causal associations were robust in various sensitivity analyses. CONCLUSIONS: Dental caries causally decrease the cerebral cortical thickness of the BANKSSTS, a cerebral cortical region crucial for language-related functions, and is the most affected brain region in Alzheimer's disease. This investigation provides the first evidence that dental caries causally affects brain structure, proving the existence of teeth-brain axes. This study also suggested that clinicians should highlight the causal effects of dental caries on brain disorders during the diagnosis and treatments, the cortical thickness of BANKSSTS is a promising diagnostic measurement for dental caries-related brain degeneration.

Moth wings are acoustic metamaterials.

Metamaterials assemble multiple subwavelength elements to create structures with extraordinary physical properties (1-4). Optical metamaterials are rare in nature and no natural acoustic metamaterials are known. Here, we reveal that the intricate scale layer on moth wings forms a metamaterial ultrasound absorber (peak absorption = 72% of sound intensity at 78 kHz) that is 111 times thinner than the longest absorbed wavelength. Individual scales act as resonant (5) unit cells that are linked via a shared wing membrane to form this metamaterial, and collectively they generate hard-to-attain broadband deep-subwavelength absorption. Their collective absorption exceeds the sum of their individual contributions. This sound absorber provides moth wings with acoustic camouflage (6) against echolocating bats. It combines broadband absorption of all frequencies used by bats with light and ultrathin structures that meet aerodynamic constraints on wing weight and thickness. The morphological implementation seen in this evolved acoustic metamaterial reveals enticing ways to design high-performance noise mitigation devices.

hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability.

DNA2 is a nuclease/helicase that is involved in Okazaki fragment maturation, replication fork processing, and end resection of DNA double-strand breaks. Similar such helicase activity for resolving secondary structures and structure-specific nuclease activity are needed during DNA replication to process the chromosome-specific higher order repeat units present in the centromeres of human chromosomes. Here, we show that DNA2 binds preferentially to centromeric DNA The nuclease and helicase activities of DNA2 are both essential for resolution of DNA structural obstacles to facilitate DNA replication fork movement. Loss of DNA2-mediated clean-up mechanisms impairs centromeric DNA replication and CENP-A deposition, leading to activation of the ATR DNA damage checkpoints at centromeric DNA regions and late-S/G2 cell cycle arrest. Cells that escape arrest show impaired metaphase plate formation and abnormal chromosomal segregation. Furthermore, the DNA2 inhibitor C5 mimics DNA2 knockout and synergistically kills cancer cells when combined with an ATR inhibitor. These findings provide mechanistic insights into how DNA2 supports replication of centromeric DNA and give further insights into new therapeutic strategies.

Requirement of Bccip for the Regeneration of Intestinal Progenitors.

BCCIP was originally identified as a BRCA2 and CDKN1A/p21 interaction protein. Although a partial loss of BCCIP function is sufficient to trigger genomic instability and tumorigenesis, complete deletion of BCCIP is lethal to cells. Using Rosa26-CreERT2 mouse models, we found that induced Bccip deletion in adult mice caused an acute intestinal epithelial denudation that cannot be relieved by co-deletion of Trp53. The critical role of Bccip in intestine epithelial renewal was verified with a Villin-CreERT2 mouse model. The epithelium degeneration was associated with a rapid loss of the proliferative capability of the crypt progenitor cells in vivo, lack of crypt base columnar stem cell markers, and a failure of in vitro crypt organoid growth. RNA-Seq analysis of freshly isolated intestinal crypt cells showed that Bccip deletion caused an overwhelming down-regulation of genes involved in mitotic cell division but an up-regulation of genes involved in apoptosis and stress response to microbiomes. Our data not only indicate that intestinal epithelium is the most sensitive tissue to whole-body deletion of Bccip but also point to Bccip as a novel and critical factor for the proliferation of the intestinal progenitors. These findings have significant implications for understanding why a hypomorphic loss of BCCIP functions is more relevant to tumorigenesis.

Models for resonant acoustic metasurfaces with application to moth wing ultrasound absorption.

Taking as bioinspiration the remarkable acoustic absorption properties of moth wings, we develop a simple analytical model that describes the interaction between acoustic pressure fields, and thin elastic plates incorporating resonant sub-structures. The moth wing is an exemplar of a natural acoustic metamaterial; the wings are deeply subwavelength in thickness at the frequencies of interest, the absorption is broadband and the tiny scales resonate on the moth wing acting in concert. The simplified model incorporates only the essential physics and the scales are idealized to flat rigid rectangular plates coupled via a spring to an elastic plate that forms the wing; all the components are deep-subwavelength at desired frequencies. Based on Fourier analysis, complemented by phenomenological modelling, our theory shows excellent agreement with simulation mimicking the moth-wing structure. Moth wings operate as broadband sound absorbers employing a range of scale sizes. We demonstrate that a random distribution of scale sizes generates a broadband absorption spectrum. To further illustrate the potential of the model, we design a deeply sub-wavelength acoustic counterpart of electromagnetically induced reflectance. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 2)'.

BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis.

Ribosome biogenesis is a fundamental process required for cell proliferation. Although evolutionally conserved, the mammalian ribosome assembly system is more complex than in yeasts. BCCIP was originally identified as a BRCA2 and p21 interacting protein. A partial loss of BCCIP function was sufficient to trigger genomic instability and tumorigenesis. However, a complete deletion of BCCIP arrested cell growth and was lethal in mice. Here, we report that a fraction of mammalian BCCIP localizes in the nucleolus and regulates 60S ribosome biogenesis. Both abrogation of BCCIP nucleolar localization and impaired BCCIP-eIF6 interaction can compromise eIF6 recruitment to the nucleolus and 60S ribosome biogenesis. BCCIP is vital for a pre-rRNA processing step that produces 12S pre-rRNA, a precursor to the 5.8S rRNA. However, a heterozygous Bccip loss was insufficient to impair 60S biogenesis in mouse embryo fibroblasts, but a profound reduction of BCCIP was required to abrogate its function in 60S biogenesis. These results suggest that BCCIP is a critical factor for mammalian pre-rRNA processing and 60S generation and offer an explanation as to why a subtle dysfunction of BCCIP can be tumorigenic but a complete depletion of BCCIP is lethal.

Phase Contrast Image-Based Rapid Antimicrobial Susceptibility Testing of Bacteria in Liquid Culture Media.

Currently, the world is facing the problem of bacterial resistance, which threatens public health, and bacterial antimicrobial susceptibility testing (AST) plays an important role in biomedicine, dietary safety and aquaculture. Traditional AST methods take a long time, usually 16-24 h, and cannot meet the demand for rapid diagnosis in the clinic, so rapid AST methods are needed to shorten the detection time. In this study, by using an in-house built centrifuge to centrifuge bacteria in a liquid medium onto the inner wall of the bottom surface of a counting plate, and using a phase contrast microscope to track bacterial growth under the effect of different antibiotic concentrations, the results of the minimum inhibitory concentration (MIC) of bacteria under the effect of antibiotics can be obtained in as early as 4 h. We used a combination of E. coli and tigecycline and obtained MIC results that were consistent with those obtained using the gold standard broth micro-dilution method, demonstrating the validity of our method; due to the time advantage, the complete set can be used in the future for point of care and clinical applications, helping physicians to quickly obtain the MIC used to inhibit bacterial growth.

Spontaneous Development of Hepatocellular Carcinoma and B-Cell Lymphoma in Mosaic and Heterozygous Brca2 and Cdkn1a Interacting Protein Knockout Mice.

Hepatocellular carcinoma (HCC) is the most common form of liver tumors. Although HCC is associated with chronic viral infections, alcoholic cirrhosis, and nonalcoholic fatty liver disease, genetic factors that contribute to the HCC risk remain unknown. The BRCA2 DNA repair associated (BRCA2) and cyclin-dependent kinase inhibitor 1A (CDKN1A) interacting protein, known as BCCIP, are essential for cell viability and maintenance of genomic stability. In this study, we established a new genetically engineered mouse model with Bccip deficiency. Mosaic or heterozygous Bccip deletion conferred an increased risk of spontaneous liver tumorigenesis and B-cell lymphoma development at old age. These abnormalities are accompanied with chronic inflammation, histologic features of nonalcoholic steatohepatitis, keratin and ubiquitin aggregates within cytoplasmic Mallory-Denk bodies, and changes of the intracellular distribution of high-mobility group box 1 protein. Our study suggests BCCIP dysregulation as a risk factor for HCC and offers a novel mouse model for future investigations of nonviral or nonalcoholic causes of HCC development.

Biomechanics of a moth scale at ultrasonic frequencies.

The wings of moths and butterflies are densely covered in scales that exhibit intricate shapes and sculptured nanostructures. While certain butterfly scales create nanoscale photonic effects, moth scales show different nanostructures suggesting different functionality. Here we investigate moth-scale vibrodynamics to understand their role in creating acoustic camouflage against bat echolocation, where scales on wings provide ultrasound absorber functionality. For this, individual scales can be considered as building blocks with adapted biomechanical properties at ultrasonic frequencies. The 3D nanostructure of a full Bunaea alcinoe moth forewing scale was characterized using confocal microscopy. Structurally, this scale is double layered and endowed with different perforation rates on the upper and lower laminae, which are interconnected by trabeculae pillars. From these observations a parameterized model of the scale's nanostructure was formed and its effective elastic stiffness matrix extracted. Macroscale numerical modeling of scale vibrodynamics showed close qualitative and quantitative agreement with scanning laser Doppler vibrometry measurement of this scale's oscillations, suggesting that the governing biomechanics have been captured accurately. Importantly, this scale of B. alcinoe exhibits its first three resonances in the typical echolocation frequency range of bats, suggesting it has evolved as a resonant absorber. Damping coefficients of the moth-scale resonator and ultrasonic absorption of a scaled wing were estimated using numerical modeling. The calculated absorption coefficient of 0.50 agrees with the published maximum acoustic effect of wing scaling. Understanding scale vibroacoustic behavior helps create macroscopic structures with the capacity for broadband acoustic camouflage.

Myriocin and d-PDMP ameliorate atherosclerosis in ApoE-/- mice via reducing lipid uptake and vascular inflammation.

Sphingolipids have been implicated in the etiology of atherosclerosis. The commonly used sphingolipid inhibitors, myriocin (a ceramide inhibitor) and d-PDMP (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, a glycosphingolipid inhibitor), have shown therapeutic potential but their efficacy and their underlying mechanisms remain unclear. Here, apolipoprotein E-deficient (apoE-/-) mice were fed a high-fat diet (HFD) and treated with a control, myriocin, d-PDMP, or atorvastatin for 12 weeks. We analyzed the effects of these drugs on the size and detailed composition of atherosclerotic plaques. Molecular biological approaches were used to explore how the inhibitors affect lipid metabolism and foam-cell formation. Treatment with myriocin or d-PDMP led to smaller and less vulnerable atherosclerotic lesions and was almost as effective as atorvastatin. Sphingolipid inhibitors down-regulated the expression of monocyte chemotactic protein 1 (MCP-1) and its receptor chemoattractant cytokine receptor 2 (CCR2), which play a key role in monocyte recruitment. They also decreased pro-inflammatory Ly-6chigh monocytes and influenced the uptake of modified LDL by down-regulating the expression of cluster of differentiation 36 (CD36) and lectin-like oxidized LDL (ox-LDL) receptor-1 (LOX-1). The inhibitors exhibited the advantage of maintaining normal glucose homeostasis compared with atorvastatin. These findings reveal for the first time that the modulation of sphingolipid synthesis can effectively alleviate atherosclerosis progression by preventing lipid uptake and reducing inflammatory responses in the arterial walls.

C-reactive protein exacerbates epithelial-mesenchymal transition through Wnt/ß-catenin and ERK signaling in streptozocin-induced diabetic nephropathy.

Previous studies have reported the pathogenic role of C-reactive protein (CRP) during diabetic kidney disease (DKD) in human CRP transgenic and Crp-/- mice. However, because humans and mice have inverse acute phase expression patterns of CRP and serum amyloid P component, this could lead to the inaccurate evaluation of CRP function with the above-mentioned CRP transgenic mouse. But different from mice, rats have the same acute phase protein expression pattern as human, which might avoid this problem and be a better choice for CRP function studies. To dispel this doubt and accurately define the role of CRP during diabetic nephropathy, we created the first Crp-/- rat model, which we treated with streptozocin to induce DKD for in vivo studies. Moreover, an established cell line (human kidney 2) was used to further investigate the pathologic mechanisms of CRP. We found that CRP promotes epithelial-mesenchymal transition (EMT) through Wnt/ß-catenin and ERK1/2 signaling, which are dependent on CRP binding to FcγRII on apoptotic cells. By promoting EMT, CRP was demonstrated to accelerate the development of DKD. We thus present convincing evidence demonstrating CRP as a therapeutic target for DKD treatment.-Zhang, L., Shen, Z.-Y., Wang, K., Li, W., Shi, J.-M., Osoro, E. K., Ullah, N., Zhou, Y., Ji, S.-R. C-reactive protein exacerbates epithelial-mesenchymal transition through Wnt/ß-catenin and ERK signaling in streptozocin-induced diabetic nephropathy.

Dual-wavelength digital holographic phase and fluorescence microscopy combining with Raman spectroscopy for micro-quartz pieces-based dual-channel encoded suspension array.

Dual-wavelength digital holographic phase and fluorescence microscopy (DW-DHPFM), combining with Raman spectroscopy, is designed to achieve the detection and analysis of biomolecules with a new dual-channel encoding method. This employs the Raman reporter molecules assembled micro-quartz pieces (MQPs) as microcarriers of suspension array (SA). The dual-wavelength digital holographic phase microscopy (DW-DHPM) and Raman spectroscopy are served as the decoding platforms, and the fluorescence microscopy is used to quantify target analytes. Considering the independence between encoding and label signal, the above two encoding channels could effectively avoid the crosstalk in immunoassay process, and the combination of two encoding methods expand the encoding capacity with a considerable magnitude. Accurate and stable decoding abilities are verified by multiplexed immunoassay experiment and the quantitative analysis of targets with high-sensitivity is confirmed by concentration gradient experiments.

Image-guided vibrometry system integrated with spectral- and time-domain optical coherence tomography.

Vibrometry using optical coherence tomography (OCT) can provide valuable information for investigating either the mechanical properties or the physiological function of biological tissues, especially the hearing organs. Real-time imaging of the measured tissues provides structure imaging and spatial guidance for and is thus highly demanded by such vibrometry. However, the traditional time-domain OCT (TD-OCT) systems, although capable of subnanometric vibrometry at large ranges of frequencies, are unable to offer an imaging speed that is high enough to acquire depth-resolved images for guidance. The spectral-domain OCT (SD-OCT) systems, although allowing image-guided vibrometry, are challenged in measuring vibration at high frequencies, particularly for scattering tissue specimens that require longer exposure time to ensure imaging and vibrometry performance. This is because of their limit in the line-scan rate of the CCD, in which the maximum resolvable frequency measured by the SD-OCT is about 1/4 of the CCD line-scan rate in practice. In the present study, we have developed a dual-mode OCT system combining both SD-OCT and TD-OCT modalities for image-guided vibrometry, as the SD-OCT can provide guiding structural images in real-time and, moreover, the TD-OCT can guarantee vibrometry at large ranges of frequencies, including high frequencies. The efficacy of the developed system in image-guided vibrometry has been experimentally demonstrated using both piezoelectric ceramic transducer (PZT) and ex vivo middle-ear samples from guinea pigs. For the vibrometry of PZT, the minimum detectable vibration amplitude was reached at ∼0.01 nm. For the vibrometry of the sound-evoked biological samples, both real-time two-dimensional imaging and subnanometric vibrometry were performed at the frequency ranging from 1 to 40 kHz. These results indicate that our dual-mode OCT system is able to act as an excellent vibrometer enabling image-guided high-frequency measurement.

A New Self-Powered Sensor Using the Radial Field Piezoelectric Diaphragm in d33 Mode for Detecting Underwater Disturbances.

This paper presents a new sensor based on a radial field bulk piezoelectric diaphragm to provide energy-efficient and high-performance situational sensing for autonomous underwater vehicles (AUVs). This sensor is self-powered, does not need an external power supply, and works efficiently in d33 mode by using inter-circulating electrodes to release the radial in-plane poling. Finite element analysis was conducted to estimate the sensor behavior. Sensor prototypes were fabricated by microfabrication technology. The dynamic behaviors of the piezoelectric diaphragm were examined by the impedance spectrum. By imitating the underwater disturbance and generating the oscillatory flow velocities with a vibrating sphere, the performance of the sensor in detecting the oscillatory flow was tested. Experimental results show that the sensitivity of the sensor is up to 1.16 mV/(mm/s), and the detectable oscillatory flow velocity is as low as 4 mm/s. Further, this sensor can work well under a disturbance with low frequency. The present work provides a good application prospect for the underwater sensing of AUVs.