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Objective: This randomized controlled and double-blind study aimed to investigate whether the analgesic effect of the adductor canal block (ACB) combined with the genicular nerve block (GNB) after total knee arthroplasty is noninferior to that of the adductor canal block combined with local infiltration analgesia (LIA). Methods: A total of 102 patients undergoing total knee arthroplasty under general anesthesia were included and randomly divided into: ACB + GNB and ACB + LIA groups; the ACB + LIA group received 80 mL of 0.2% ropivacaine with adrenaline 10 µg/mL for LIA, whereas the ACB + GNB group received 4 mL of 0.2% ropivacaine for the blockade of five peri-knee nerves. The primary outcome was the median difference in the visual analog scale scores at rest at 24 h between the two groups. Secondary outcomes involved the median differences in the pain scores at other time points. Other outcomes included the cumulative dosage of opioids calculated in morphine equivalents in the first 24 h and indicators related to knee joint functional recovery. Results: In total, 36 and 38 patients were included in the ACB + GNB and ACB + LIA groups, respectively. We found that the median difference (95% confidence internal) in postoperative rest pain at 24 h (noninferiority criteria, △ = 1) was − 0.5 (− 1 to 0, p = 0.002). The median difference in cumulative opioid consumption was 1 mg (− 1 to 3, p = 0.019), meeting the noninferiority criteria, △ = 7.7 mg. Conclusions: ACB combined with GNB provides noninferior analgesia compared to ACB with LIA on the first day after total knee arthroplasty while significantly reducing local anesthetic use. Trial registration: Name of the Registry: Chinese Clinical Trial Registry; Trial Registration Number: ChiCTR2300074274; Date of Registration. August 2, 2023. [ABSTRACT FROM AUTHOR]

Ultrasound switchable fluorescence (USF) imaging, a hybrid imaging technology that combines the advantages of both fluorescence sensitivity and acoustic resolution in centimeter‐deep tissue, has great potential for biomedical different applications. A camera‐based USF imaging system reveals its capability of capturing both spatial and temporal dynamics of the USF signal in tissue. In this study, various algorithms were explored to enhance the spatial resolution and signal‐to‐noise ratio (SNR) of USF images, utilizing temporal and spatial information from a camera‐based time‐domain USF imaging system. The correlation method proved effective in boosting SNR, while the ascending‐slope‐weighted method enhanced spatial resolution. Additionally, the spatially back‐projection method significantly improved spatial resolution in silicone phantoms. The results underscore the advantages of incorporating temporal and spatial information from USF signals. [ABSTRACT FROM AUTHOR]

Temperature measurements in biological tissues play a crucial role in studying metabolic activities. In this study, we introduce a noninvasive thermometry technique based on two‐color ultrasound‐switchable fluorescence (USF). This innovative method allows for a local temperature mapping within a microtube filled with temperature‐sensitive liposomes as nano imaging agents. By measuring the temperature‐dependent fluorescence emission of the liposomes using a spectrometer, we identify four characteristic temperatures. The local background temperature can be estimated by analyzing the corresponding appearance time of these four characteristic temperatures in the dynamic USF signals captured by a camera‐based USF system with two detection channels. Simultaneous measurements with an infrared (IR) camera showed a 0.38°C ± 0.27°C difference between USF thermometry and IR thermography in a physiological temperature range of 36.48°C–40.14°C. This shows that the two‐color USF thermometry technique is a reliable, noninvasive tool with excellent spatial and thermal resolution. [ABSTRACT FROM AUTHOR]

The demand for measuring fluorophore temperature sensitivity and temperature change in chemical or biological samples has spurred the search for effective methods. While infrared (IR) light-based thermal devices are popular, they are limited to surface temperature measurement. Fluorescence-based thermometry, which utilizes intensity, lifetime, polarization, and spectrum change, provides the temperature information directly from the samples and can have high temporal and spatial resolution. However, measuring fluorescence can be tricky and expensive. A cost-effective approach to achieving reasonable accuracy is highly desired. This study introduces such an approach, employing a light-emitting diode (LED) for fluorophore excitation and a laser diode (LD) for sample heating, with a phone camera recording fluorescence changes. A data processing method converts the video into digital data, processed through digital filters. Utilizing a small-volume cuvette enhances heating efficiency. This study serves as a practical guide for inexperienced individuals, including students, instructors, and researchers, facilitating entry into the field and navigating the complexities of fluorescence-based thermometry. [ABSTRACT FROM AUTHOR]

Clostridium perfringens is the etiological agent for necrotic enteritis (NE) in broiler chickens, which causes a substantial economic loss of an estimated USD 6 billion annually in the global poultry industry. Collagen adhesion is involved in the NE pathogenesis in poultry. In this study, the binding capabilities of chicken C. perfringens isolates of various genetic backgrounds (netB−tpeL−, netB+tpeL−, netB+tpeL+) to collagen types I–V and gelatin were examined, and the putative adhesin protein cnaA gene was investigated at the genomic level. In total, 28 C. perfringens strains from healthy and NE-inflicted sick chickens were examined. The results on collagen adhesin-encoding gene cnaA by the quantitative-PCR results indicated that netB−tpeL− isolates had much lower copies of the detectable cnaA gene than netB+ isolates (10 netB+tpeL− isolates, 5 netB+tpeL+ isolates). Most of the virulent C. perfringens isolates demonstrated collagen-binding abilities to types I–II and IV–V, while some strains showed weak or no binding to collagen type III and gelatin. However, the netB+tpeL+ isolates showed significantly higher binding capabilities to collagen III than netB−tpeL− and netB+tpeL− isolates. The data in this study suggest that the collagen-binding capability of clinical C. perfringens isolates correlates well with their NE pathogenicity levels, especially for C. perfringens isolates carrying genes encoding crucial virulence factors and virulence-associated factors such as netB, cnaA, and tpeL. These results indicate that the presence of the cnaA gene may be correlated with C. perfringens virulence (particularly for netB+ isolates). [ABSTRACT FROM AUTHOR]

Near-infrared fluorescence imaging has emerged as a noninvasive, inexpensive, and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy. In particular, ultrasound switchable fluorescence (USF) imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues. This study achieved the size control of polymer-based and indocyanine green (ICG) encapsulated USF contrast agents, capable of accumulating in the tumor after intravenous injections. These nanoprobes varied in size from 58 to 321 nm. The bioimaging profiles demonstrated that the proposed nanoparticles can efficiently eliminate the background light from normal tissue and show a tumor-specific fluorescence enhancement in the BxPC-3 tumor-bearing mice models possibly via the enhanced permeability and retention effect. In vivo tumor USF imaging further demonstrated that these nanoprobes can effectively be switched "ON" with enhanced fluorescence in response to a focused ultrasound stimulation in the tumor microenvironment, contributing to the high-resolution USF images. Therefore, our findings suggest that ICG-encapsulated nanoparticles are good candidates for USF imaging of tumors in live animals, indicating their great potential in optical tumor imaging in deep tissue. [ABSTRACT FROM AUTHOR]

Liposomes have been widely used in both medical imaging and drug delivery fields due to their excellent biocompatibility and easy surface modification. Recently our lab reported for the first-time the implementation of temperature-sensitive and indocyanine green (ICG)-encapsulated liposome microparticles for in vivo ultrasound-switchable fluorescence (USF) imaging. A previous study showed that liposome microparticles achieved USF imaging in centimeter-deep tissue. This study aimed to control the size of liposomes at the nanoscale and study the size effect on the USF imaging depth. Also, we explored the feasibility of combining USF imaging with ultrasound-controlled release. Liposomes were synthesized via the hydration method and the size was controlled by an extruding process. Characterization parameters, including fluorescence profile, spectra, size, stability, encapsulation efficiency, and ultrasound-controlled release, were evaluated. USF imaging in blood serum was conducted successfully in a phantom model, and an imaging depth study was conducted at 1.0 cm and 2.5 cm and confirmed that nano-sized liposomes had a stronger USF signal than micron-sized liposomes. Additionally, releasing tests indicated that both ultrasound power and exposure time affected the release efficiency in that increasing the power and extending the exposure time led to higher release efficiency. Above all, this study shows the potential for using liposomes for USF imaging and ultrasound-controlled release. [ABSTRACT FROM AUTHOR]

Purpose: Cathepsin L (CTSL) and B (CTSB) were lysosomal proteases, and their expression and activity contribute to the progression of inflammation in obese rodents. Our aim was to investigate CTSB and CTSL expression in omental adipose tissue (AT) of patients with obesity and to correlate CTSB and CTSL expression with proinflammatory cytokines (CCL-2, IL-6 and IL-1β). Patients and Methods: A total of 12 patients without obesity (NOB) and 51 patients with obesity (OB) were involved in this study. Omental AT was collected from all the participants for RNA extraction. Expressions of CTSB, CTSL and proinflammatory cytokines (CCL-2, IL-6 and IL-1β) were qualified with qRT-PCR. BMI (body mass index) and metabolic parameters were measured. Results: The mRNA expression levels of both CTSB and CTSL were upregulated in the OB group (t = 2.693, P < 0.05; t = 2.849, P< 0.01) and were related to TC levels (Std.β=0.443, P< 0.05; Std.β=0.439, P< 0.05). However, only the CTSB level was related to BMI (Std.β=0.261, P< 0.05). In multiple regression analysis, CTSL was independently associated with CCL-2, IL-6 and IL-1β levels (Std.β=0.352– 0.462, P< 0.05). Conclusion: CTSB and CTSL gene expressions were elevated in the omental AT of OB group. CTSL, but not CTSB, was positively correlated with proinflammatory cytokines independently, suggesting that the dysregulation of CTSL may play a significant role in the inflammatory process. [ABSTRACT FROM AUTHOR]

Necrotic enteritis (NE) is a multifactorial and important enteric infectious disease etiologically caused by pathogenic C. perfringens infection, accounting for the estimated loss of around USD 6 billion in the global poultry industry. The increasing incidence of NE was found to be associated with the voluntary reduction or withdrawal of antibiotic growth promoters from animal feed during recent years. Therefore, the development of effective vaccines specific to NE assumes a priority for the poultry industry. This study aimed to identify the potential C. perfringens proteins as vaccine targets for NE. Three recombinant C. perfringens proteins targeting five antigens were prepared: two chimeric proteins (alpha-toxin and NetB, fructose-1,6-bisphosphate aldolase (FBA) and a zinc metalloprotease (Zm)), and one single collagen adhesion protein (Cna). Their protection efficacies were evaluated with a potent challenge model of Eimeria maxima/C. perfringens dual infections using a netB+tpeL+ C. perfringens strain. Young chicks were immunized twice subcutaneously with adjuvanted C. perfringens proteins on Days 4 and 15. At six days after the second immunization, the chickens immunized with Cna, FBA, and Zm antigens, and alpha-toxin had much higher serum antibody titers than unvaccinated controls prior to the challenge. Following the challenge, the pooled antigen-immunized group demonstrated no mortality and the least lesion scores against virulent challenge. The results indicate that the immunization with multicomponent antigens, including C. perfringens housekeeping protein Cna, may confer partial protection. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound-guided thoracic paravertebral block (TPVB) has become increasingly popular for postoperative analgesia after thoracic surgery. We designed this prospective, randomized, double-blind, placebo-controlled trial to investigate the effect of TPVB on blood coagulation in patients after thoracoscopic lobectomy. Patients and Methods: Sixty patients scheduled for thoracoscopic lobectomy were randomly allocated to two groups. Patients underwent ultrasound-guided TPVB with 0.33% ropivacaine (T group) or 0.9% saline (C group) at the end of the surgery under general anesthesia. Patient-controlled intravenous analgesia (PCIA) was administered for both group after the surgery. The primary outcome was the thromboelastogram (TEG) parameters before anesthesia (T0), at the end of operation (T1) and in 1 day (T2) and 2 days (T3) after the operation, the second outcomes were the analgesic effect and the amount of intraoperative opioid consumption, operation time, infusion volume, blood loss and urine volume. Results: The visual analog scale (VAS) scores in group T were lower than group C (P < 0.05). In group T, compared with T0, the R value at T1 and T2 is significantly reduced, and the K value at T1 were significantly shortened, the α-angle and MA value at T1 were significantly increased (P < 0.05). In group C, compared with T0, the R value and K value were significantly shortened, the α-angle and MA value were significantly increased at all postoperative time points (P < 0.05). Compared with group C at the same time point, the R and K values of group T were significantly longer, and the α-angle and MA values were significantly reduced at T2 and T3 points, with statistically significant differences (P< 0.05). Conclusion: TPVB is beneficial to improve postoperative hypercoagulability and promote postoperative rehabilitation of patients after thoracoscopic lobectomy. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells. [ABSTRACT FROM AUTHOR]

One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep tissue. Ultrasound-switchable fluorescence (USF) imaging is a novel imaging tool that has recently been explored to possibly surmount the above-mentioned bottleneck. Herein, a β-cyclodextrin/indocyanine green (ICG) complex-encapsulated poly(N-isopropylacrylamide) (PNIPAM) nanogel was synthesized and studied for ex vivo/in vivo deep tissue/high-resolution near infrared USF (NIR-USF) imaging. To be specific, our results revealed that the average diameter of the as-prepared nanogels was significantly decreased to ~ 32 nm from ~ 335 nm compared to the reported ICG-PNIPAM nanoparticles. Additionally, the excitation/ emission characteristics of the ICG itself in present nanogels were almost completely retained, and the resultant nanogel exhibited high physiological stability and positive biocompatibility. In particular, the signal-to-noise ratio of the USF image for the PNIPAM/ β-cyclodextrin/ICG nanogel (33.01 ± 2.42 dB) was prominently higher than that of the ICG-PNIPAM nanoparticles (18.73 ± 0.33 dB) in 1.5-cm-thick chicken breast tissues. The NIR-USF imaging in 3.5-cm-thick chicken breast tissues was achieved using this new probe. The ex vivo NIR-USF imaging of the mouse liver was also successfully obtained. Animal experiments showed that the present nanogels were able to be effectively accumulated into U87 tumor-bearing mice via enhanced permeability and retention effects, and the high-resolution NIR-USF imaging of in vivo tumor was efficiently acquired. The metabolism and in vivo biodistribution of the nanogels were evaluated. Overall, the results suggest that the current nanogel is a highly promising NIR-USF probe for deep tissue and high-resolution USF imaging. [ABSTRACT FROM AUTHOR]

To understand the modulation mechanisms of fluorescence emission induced by ultrasonic waves in turbid media, a mathematical model is proposed and compared with the recent experimental observations of Kobayashi et al. [Appl. Phys. Lett. 89, 181102 (2006)]. Modulation of fluorophore concentration is considered as the source of the oscillation of fluorescence signals when fluorophore concentration is low enough so that quenching effects can be ignored. By solving the rate equation and photon diffusion equation, quantitative solutions are given to quantify the modulation strength. Our calculations predict that the modulation depth (the ratio of the modulated signal strength to the unmodulated signal strength) can reach 10-4 when ultrasonic pressure with the order of magnitude of megapascals is applied in the ultrasound focal zone. Our model explains the relationship between the modulation strength and the average fluorophore concentration and also predicts a method to measure or image fluorescence lifetime in the turbid medium. When fluorophore concentration is high enough so that fluorescence quenching occurs, the fluorescence modulation is attributed to the modulation of quenching efficiency. Quenching caused by fluorescence resonance energy transfer can lead to a nonlinear relationship between the modulation fluorescence strength and the applied ultrasound strength. [ABSTRACT FROM AUTHOR]

Resonance of space-charge field can occur in photorefractive polymers through a moving fringe and can be described by a forced oscillation equation with damping. The resonance frequency and the magnitudes of both the amplitude and the imaginary part of the space-charge field at the resonance frequency are functions of three experimental parameters: total incident intensity, applied electric field, and grating wave vector. Thus, the diffraction efficiency of grating and the gain coefficient of two-wave mixing are dependent on the three experimental parameters. Our theory can also be applied to inorganic photorefractive crystals. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

For many years, investigators have sought after high-resolution fluorescence imaging in centimeter-deep tissue because many interesting in vivo phenomena—such as the presence of immune system cells, tumor angiogenesis, and metastasis—may be located deep in tissue. Previously, we developed a new imaging technique to achieve high spatial resolution in sub-centimeter deep tissue phantoms named continuous-wave ultrasound-switchable fluorescence (CW-USF). The principle is to use a focused ultrasound wave to externally and locally switch on and off the fluorophore emission from a small volume (close to ultrasound focal volume). By making improvements in three aspects of this technique: excellent near-infrared USF contrast agents, a sensitive frequency-domain USF imaging system, and an effective signal processing algorithm, for the first time this study has achieved high spatial resolution (~ 900 μm) in 3-centimeter-deep tissue phantoms with high signal-to-noise ratio (SNR) and high sensitivity (3.4 picomoles of fluorophore in a volume of 68 nanoliters can be detected). We have achieved these results in both tissue-mimic phantoms and porcine muscle tissues. We have also demonstrated multi-color USF to image and distinguish two fluorophores with different wavelengths, which might be very useful for simultaneously imaging of multiple targets and observing their interactions in the future. This work has opened the door for future studies of high-resolution centimeter-deep tissue fluorescence imaging. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is characterized by dysregulated immune responses in inflamed intestine, with dominance of interleukin-17 ( IL-17) -producing cells and deficiency of regulatory T (Treg) cells. The aim of this study was to investigate the effect and mechanisms of sirolimus, an inhibitor of the mammalian target of rapamycin, on immune responses in a murine model of Crohn's disease. Murine colitis was induced by intrarectal administration of 2,4,6-trinitrobenzene sulphonic acid at day 0. Mice were then treated intraperitoneally with sirolimus daily for 3 days. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. Sirolimus treatment significantly decreased all macroscopic, microscopic and histopathological parameters of colitis that were analysed. The therapeutic effects of sirolimus were associated with a down-regulation of pro-inflammatory cytokines tumour necrosis factor-α, IL-6 and IL-17A. Intriguingly, sirolimus administration resulted in a prominent up-regulation of the regulatory cytokine transforming growth factor-β. Supporting the hypothesis that sirolimus directly affects the functional activity of CD4+ CD25+ Treg cells, we observed a remarkable enhancement of FoxP3 expression in colon tissues and isolated CD4+ T cells of sirolimus-treated mice. Simultaneously, sirolimus treatment led to a significant reduction in the number of CD4+ IL-17A+ T cells in the mesenteric lymph node cells as well as IL-17A production in mesenteric lymph node cells. Therefore, sirolimus may offer a promising new therapeutic strategy for the treatment of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Our recently developed ultrasound-switchable fluorescence (USF) imaging technique showed that it was feasible to conduct high-resolution fluorescence imaging in a centimeter-deep turbid medium. Because the spatial resolution of this technique highly depends on the ultrasound-induced temperature focal size (UTFS), minimization of UTFS becomes important for further improving the spatial resolution USF technique. In this study, we found that UTFS can be significantly reduced below the diffraction-limited acoustic intensity focal size via nonlinear acoustic effects and thermal confinement by appropriately controlling ultrasound power and exposure time, which can be potentially used for deep-tissue high-resolution imaging. [ABSTRACT FROM AUTHOR]

Laminar optical tomography (LOT) is a new three-dimensional in vivo functional optical imaging technique. Adopting a microscopy-based setup and diffuse optical tomography (DOT) imaging principles, LOT can perform both absorption- and fluorescence-contrast imaging with higher resolution (100–200 μm) than DOT and deeper penetration (2–3 mm) than laser scanning microscopy. These features, as well as a large field of view and acquisition speeds up to 100 frames per second, make LOT suitable for depth-resolved imaging of stratified tissues such as retina, skin, endothelial tissues and the cortex of the brain. In this paper, we provide a detailed description of a new LOT system design capable of imaging both absorption and fluorescence contrast, and present characterization of its performance using phantom studies. [ABSTRACT FROM AUTHOR]

Clostridium perfringens is an important opportunistic pathogen that may result in toxin-mediated diseases involving food poisoning/tissue gangrene in humans and various enterotoxaemia in animal species. It is a main etiological agent for necrotic enteritis (NE), the most financially devastating bacterial disease in broiler chickens, especially if raised under antibiotic-free conditions. Importantly, NE is responsible for losses of six billion US dollars annually in the global poultry industry. To investigate the molecular mechanisms of C. perfringens-induced pathogenesis in the gut and its microbiome mRNA levels in C. perfringens-infected and non-infected hosts, we used RNA sequencing technology to perform transcriptional analysis of both host intestine and microbiome using our NE model. The growth rate was significantly impaired in chickens infected by C. perfringens. In total, 13,473 annotated chicken genes were differentially expressed between these two groups, with ninety-six genes showing statistical significance (|absolute fold changes| > 2.0, adjusted p value < 0.05). Genes involved in energy production, MHC Class I antigen, translation, ribosomal structures, and amino acid, nucleotide and carbohydrate metabolism from infected gut tissues were significantly down-regulated. The upregulated genes were mainly engaged in innate and adaptive immunity, cellular processes, genetic information processing, and organismal systems. Additionally, the transcriptional levels of four crucial foodborne pathogens were significantly elevated in a synergic relationship with pathogenic C. perfringens infection. This study presents the profiling data that would likely be a relevant reference for NE pathogenesis and may provide new insights into the mechanism of host-pathogen interaction in C. perfringens-induced NE infection in broiler chickens. [ABSTRACT FROM AUTHOR]

It is predicted that grey spatial solitons can exist in biased photorefractive polymer. The functional relationships of the transverse velocity, spatial width and phase profile of these grey solitons with their normalized intensity and degree of 'greyness' are obtained. The polarization properties of these grey solitons are discussed. The intensity full width at half maximum of these grey solitons is found to be inversely proportional to the absolute value of the external bias field. [ABSTRACT FROM AUTHOR]

In this paper, after considering the dependence of quantum efficiency of charge generation, carrier mobility, and trapping rate on the applied electric field, the relations of steady state space-charge field and response rates of space-charge field are discussed with respect to the applied electric field in photorefractive polymers. It is found that the steady state properties of the space-charge field with respect to the applied electric field are in agreement with those of inorganic photorefractive crystals. However, for the transient processes, there are different function forms between the response rates and the applied electric field, such as superlinear functions and sublinear functions. Also, the response rates are determined by the properties of traps. [ABSTRACT FROM AUTHOR]

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic–ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic–ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53–PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic–ischemic encephalopathy. [ABSTRACT FROM AUTHOR]

The feasibility of using ultrasound to modulate fluorescence in a turbid medium is still in debate due to the difficulty of detecting the modulated signal. We have demonstrated a system that could detect the weak signals of ultrasound-modulated fluorescence (UMF) by using a broadband lock-in amplifier and microbubbles as enhancement agents. By detecting the microbubble-enhanced UMF signal, a sub-millimeter fluorescent tube submerged in a turbid medium with a depth of 2 cm has been clearly observed with an ultrasonic spatial resolution. The modulation efficiency was significantly improved by using microbubbles, and was found to linearly increase with the drive voltage applied to the ultrasound transducer and the fluorophore concentration within the range adopted in this study. Possible modulation mechanisms are discussed. [ABSTRACT FROM AUTHOR]

Background: Interleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action.Methods: The brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia and treated with IL-33 at a dose of 0.2 μg/day i.p. for 3 days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells and cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes.Results: The expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 days after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation.Conclusions: The activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner. [ABSTRACT FROM AUTHOR]

Because of their deep penetration capability in tissue, red or near infrared (NIR) fluorophores attract much attention in bio-optical imaging. Among these fluorophores, the ones that respond to the immediate microenvironment (i.e., temperature, polarity, pH, viscosity, hypoxia, etc.) are highly desirable. We studied the response of six NIR aza-BODIPY-based and structurally similar fluorophores to polarity and viscosity for incorporation inside Pluronic nanoparticles as switchable fluorescent probes (SFPs). Based on our results, all of these fluorophores were moderately to strongly sensitive to the polarity of the microenvironment. We concluded that attaching amine groups to the fluorophore is not necessary for having strong polarity sensitive probes. We further studied the response of the fluorophores when embedded inside Pluronic nanoparticles and found that four of them qualified as SFPs. We also found that the switching ratio of the fluorophore-encapsulated Pluronic nanoparticles (ION-to-IOFF) is related to the length of the hydrophobic chain of the Pluronic tri-block copolymers. As such, the highest switching ratio pertained to F-68 with the lowest hydrophobic block poly (propylene oxide) (PPO chain of only 30 units). [ABSTRACT FROM AUTHOR]

We derive a kinetic differential equation for the formation of space-charge field (SCF) in photorefractive polymers and give its general solution, which is based on Schildkraut's work. It is found that SCF consists of two exponential decay waves and there are two decay factors corresponding to two response time constants of SCF. Changing the parameters in the solution, we can understand the formation of SCF for different cases. In this article, we discuss a case of no traps and find that both static and transient actions of SCF are determined by the grating wave vector k and total incident intensity I[sub i]. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Fluorescence imaging in centimeter-deep tissues with high resolution is highly desirable for many biomedical applications. Recently, we have developed a new imaging modality, ultrasound-switchable fluorescence (USF) imaging, for achieving this goal. In our previous work, we successfully achieved USF imaging with several types of USF contrast agents and imaging systems. In this study, we introduced a new USF imaging system: an intensified charge-coupled device (ICCD) camera-based, time-domain USF imaging system. We demonstrated the principle of time-domain USF imaging by using two USF contrast agents. With a series of USF imaging experiments, we demonstrated the tradeoffs among different experimental parameters (i.e., data acquisition time, including CCD camera recording time and intensifier gate delay; focused ultrasound (FU) power; and imaging depth) and the image qualities (i.e., signal-to-noise ratio, spatial resolution, and temporal resolution). In this study, we also discussed several imaging strategies for achieving a high-quality USF image via this time-domain system. [ABSTRACT FROM AUTHOR]

The conventional fluorescence imaging has limited spatial resolution in centimeter-deep tissue because of the tissue's high scattering property. Ultrasound-switchable fluorescence (USF) imaging, a new imaging technique, was recently proposed to realize high-resolution fluorescence imaging in centimeter-deep tissue. However, in vivo USF imaging has not been achieved so far because of the lack of stable near-infrared contrast agents in a biological environment and the lack of data about their biodistributions. In this study, for the first time, we achieved in vivo USF imaging successfully in mice with high resolution. USF imaging in porcine heart tissue and mouse breast tumor via local injections were studied and demonstrated. In vivo and ex vivo USF imaging of the mouse spleen via intravenous injections was also successfully achieved. The results showed that the USF contrast agent adopted in this study was very stable in a biological environment, and it was mainly accumulated into the spleen of the mice. By comparing the results of CT imaging and the results of USF imaging, the accuracy of USF imaging was proved. [ABSTRACT FROM AUTHOR]

Background: IL-33 is a pleiotropic cytokine of the IL-1 family, which has been reported to implicate in both innate and adaptive immune responses. Recent studies suggest IL-33 is crucial for regulation of myelopoiesis and myeloid cell activity. Here, we explore the potential effect of IL-33 against hematopoietic injury after total body irradiation (TBI). Methods: C57BL/6 mice were irradiated with a sublethal dose of radiation (600 cGy) and treated with IL-33 at a dose of 3 μg/dose i.p. once a day for seven consecutive days. H&E staining was used to determine the bone marrow cellularity. A flow cytometer was used to quantify the hematopoietic stem cell (HSC) population, cell proliferation, and apoptosis. The colony-forming assay was used to evaluate the clonogenic function of HSCs. RT-qPCR was used to determine the expression of apoptosis-associated genes. Results: Bone marrow HSCs from wild-type mice expressed functional IL-33 receptor (ST2), and treatment with IL-33 promoted the recovery of the HSC pool in vivo and improved the survival of mice after TBI. Conversely, mice with ST2 deficiency showed decreased HSC regeneration and mouse survival after TBI. Of note, IL-33 reduced radiation-induced apoptosis of HSCs and mediated this effect through repression of the p53-PUMA pathway. Conclusions: IL-33 regulates HSC regeneration after myelosuppressive injury through protecting HSCs from apoptosis and enhancing proliferation of the surviving HSCs. [ABSTRACT FROM AUTHOR]

The spatial resolution of fluorescence imaging techniques in deep optically turbid media such as tissues is limited by photon diffusion. To break the diffusion limit and achieve high-resolution and deep-tissue fluorescence imaging, a fundamentally different method was demonstrated based on a concept of ultrasound-switchable fluorescence. The results showed that a small fluorescent tube with a diameter of ∼180 μm at a depth of ∼20 mm in an optical scattering medium (μs′≈3.2 and μa≈0.026 cm-1) can be clearly imaged with a size of ∼260 μm. The depth-to-resolution ratio is shown to be about one order of magnitude better than other deep-tissue fluorescence imaging techniques. [ABSTRACT FROM AUTHOR]