1,366 research outputs found

    Noninvasive Submillimeter-Precision Brain Stimulation by Optically-Driven Focused Ultrasound

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    High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited millimeter-level precision. Here, we report an optically-driven focused ultrasound (OFUS) for non-invasive brain stimulation with submillimeter precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with a lateral resolution of 83 micrometers, which is two orders of magnitude smaller than that of conventional transcranial focused ultrasound (tFUS). Effective OFUS neurostimulation in vitro with a single ultrasound cycle is shown. Submillimeter transcranial stimulation of mouse motor cortex in vivo is demonstrated. An acoustic energy of 0.02 J/cm^2, two orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. By delivering a submillimeter focus non-invasively, OFUS opens a new way for neuroscience studies and disease treatments.Comment: 36 pages, 5 main figures, 13 supplementary figure

    Tim-3 Negatively Regulates IL-12 Expression by Monocytes in HCV Infection

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    T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a newly identified negative immunomodulator that is up-regulated on dysfunctional T cells during viral infections. The expression and function of Tim-3 on human innate immune responses during HCV infection, however, remains poorly characterized. In this study, we report that Tim-3 is constitutively expressed on human resting CD14+ monocyte/macrophages (M/MØ) and functions as a cap to block IL-12, a key pro-inflammatory cytokine linking innate and adaptive immune responses. Tim-3 expression is significantly reduced and IL-12 expression increased upon stimulation with Toll-like receptor 4 (TLR4) ligand - lipopolysaccharide (LPS) and TLR7/8 ligand - R848. Notably, Tim-3 is over-expressed on un-stimulated as well as TLR-stimulated M/MØ, which is inversely associated with the diminished IL-12 expression in chronically HCV-infected individuals when compared to healthy subjects. Up-regulation of Tim-3 and inhibition of IL-12 are also observed in M/MØ incubated with HCV-expressing hepatocytes, as well as in primary M/MØ or monocytic THP-1 cells incubated with HCV core protein, an effect that mimics the function of complement C1q and is reversible by blocking the HCV core/gC1qR interaction. Importantly, blockade of Tim-3 signaling significantly rescues HCV-mediated inhibition of IL-12, which is primarily expressed by Tim-3 negative M/MØ. Tim-3 blockade reduces HCV core-mediated expression of the negative immunoregulators PD-1 and SOCS-1 and increases STAT-1 phosphorylation. Conversely, blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation. These findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through crosstalk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection

    Combined Toxicity Evaluation of Ochratoxin A and Aflatoxin B1 on Kidney and Liver Injury, Immune Inflammation, and Gut Microbiota Alteration Through Pair-Feeding Pullet Model

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    Ochratoxin A (OTA) and aflatoxin B1 (AFB1) are often co-contaminated, but their synergistic toxicity in poultry is limitedly described. Furthermore, the traditional ad libitum feeding model may fail to distinguish the specific impact of mycotoxins on the biomarkers and the indirect effect of mildew on the palatability of feed. A pair-feeding model was introduced to investigate the specific effect and the indirect effect of the combined toxicity of OTA and AFB1, which were independent and dependent on feed intake, respectively. A total of 180 one-day-old pullets were randomly divided into 3 groups with 6 replicates, and each replicate contained 10 chicks. The control group (Group A) and the pair-feeding group (Group B) received the basal diet without mycotoxin contamination. Group C was administrated with OTA- and AFB1-contaminated feed (101.41 μg/kg of OTA + 20.10 μg/kg of AFB1). The scale of feeding in Group B matched with the feed intake of Group C. The trial lasted 42 days. Compared with the control group, co-contamination of OTA and AFB1 in feed could adversely affect the growth performance (average daily feed intake (ADFI), body weight (BW), average daily weight gain (ADG), feed conversion ratio (FCR), and shank length (SL)), decrease the relative weight of the spleen (p < 0.01), and increase the relative weight of the kidney (p < 0.01). Moreover, the reduction of feed intake could also adversely affect the growth performance (BW, ADG, and SL), but not as severely as mycotoxins do. Apart from that, OTA and AFB1 also activated the antioxidative and inflammation reactions of chicks, increasing the level of catalase (CAT), reactive oxygen species (ROS), and interleukin-8 (IL-8) while decreasing the level of IL-10 (p < 0.01), which was weakly influenced by the feed intake reduction. In addition, OTA and AFB1 induced histopathological changes and apoptosis in the kidney and liver as well as stimulated the growth of pernicious bacteria to cause toxic effects. There were no histopathological changes and apoptosis in the kidney and liver of the pair-feeding group. The combined toxicity of OTA and AFB1 had more severe effects on pullets than merely reducing feed supply. However, the proper reduction of the feed intake could improve pullets’ physical health by enriching the bacteria Lactobacillus, Phascolarctobacterium, Bacteroides, Parabacteroides, and Barnesiella

    Bond-Selective Intensity Diffraction Tomography

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    Recovering molecular information remains a grand challenge in the widely used holographic and computational imaging technologies. To address this challenge, we developed a computational mid-infrared photothermal microscope, termed Bond-selective Intensity Diffraction Tomography (BS-IDT). Based on a low-cost brightfield microscope with an add-on pulsed light source, BS-IDT recovers both infrared spectra and bond-selective 3D refractive index maps from intensity-only measurements. High-fidelity infrared fingerprint spectra extraction is validated. Volumetric chemical imaging of biological cells is demonstrated at a speed of ~20 seconds per volume, with a lateral and axial resolution of ~350 nm and ~1.1 micron, respectively. BS-IDT's application potential is investigated by chemically quantifying lipids stored in cancer cells and volumetric chemical imaging on Caenorhabditis elegans with a large field of view (~100 micron X 100 micron)

    Multiwindow SRS imaging using a rapid widely tunable fiber laser

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    Spectroscopic stimulated Raman scattering (SRS) imaging has become a useful tool finding a broad range of applications. Yet, wider adoption is hindered by the bulky and environmentally sensitive solid-state optical parametric oscillator (OPO) in a current SRS microscope. Moreover, chemically informative multiwindow SRS imaging across C-H, C-D, and fingerprint Raman regions is challenging due to the slow wavelength tuning speed of the solid-state OPO. In this work, we present a multiwindow SRS imaging system based on a compact and robust fiber laser with rapid and wide tuning capability. To address the relative intensity noise intrinsic to a fiber laser, we implemented autobalanced detection, which enhances the signal-to-noise ratio of stimulated Raman loss imaging by 23 times. We demonstrate high-quality SRS metabolic imaging of fungi, cancer cells, and Caenorhabditis elegans across the C-H, C-D, and fingerprint Raman windows. Our results showcase the potential of the compact multiwindow SRS system for a broad range of applications.R35 GM136223 - NIGMS NIH HHS; R01 AI141439 - NIAID NIH HHS; R01 CA224275 - NCI NIH HHSAccepted manuscrip

    Chinese Massage Combined with Herbal Ointment for Athletes with Nonspecific Low Back Pain: A Randomized Controlled Trial

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    Non-specific low back pain (NLBP) is an increasing health problem for athletes. This randomized controlled trial was designed to investigate the effects of Chinese massage combined with herbal ointment for NLBP. 110 athletes with NLBP were randomly assigned to experimental group with Chinese massage combined with herbal ointment or control group with simple massage therapy. The primary outcome was pain by Chinese Short Form McGill Pain Questionnaire (C-SFMPQ). The secondary outcome was local muscle stiffness by Myotonometer. After 4 weeks, the experimental group experienced significant improvements in C-SFMPQ and in local muscle stiffness compared with control group (between-group difference in mean change from baseline, −1.24 points, P = 0.005 in sensory scores; −3.14 points, P < 0.001 in affective scores; −4.39 points, P < 0.001 in total scores; −0.64 points, P = 0.002 in VAS; −1.04 points, P = 0.005 in local muscle stiffness during relaxation state). The difference remained at one month followup, but it was only significant in affective scores (−2.83 points, P < 0.001) at three months followup. No adverse events were observed. These findings suggest that Chinese massage combined with herbal ointment may be a beneficial complementary and alternative therapy for athletes with NLBP

    Burden of Pneumonia and Meningitis Caused by Streptococcus pneumoniae in China among Children under 5 Years of Age: A Systematic Literature Review

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    BACKGROUND AND METHODS: To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae-attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials. RESULTS: Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114-4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638-23,904) and 75 (9-370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845-1,216,918) and 28,542 (7,136-49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted
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