168 research outputs found
TIMS: A Tactile Internet-Based Micromanipulation System with Haptic Guidance for Surgical Training
Microsurgery involves the dexterous manipulation of delicate tissue or
fragile structures such as small blood vessels, nerves, etc., under a
microscope. To address the limitation of imprecise manipulation of human hands,
robotic systems have been developed to assist surgeons in performing complex
microsurgical tasks with greater precision and safety. However, the steep
learning curve for robot-assisted microsurgery (RAMS) and the shortage of
well-trained surgeons pose significant challenges to the widespread adoption of
RAMS. Therefore, the development of a versatile training system for RAMS is
necessary, which can bring tangible benefits to both surgeons and patients.
In this paper, we present a Tactile Internet-Based Micromanipulation System
(TIMS) based on a ROS-Django web-based architecture for microsurgical training.
This system can provide tactile feedback to operators via a wearable tactile
display (WTD), while real-time data is transmitted through the internet via a
ROS-Django framework. In addition, TIMS integrates haptic guidance to `guide'
the trainees to follow a desired trajectory provided by expert surgeons.
Learning from demonstration based on Gaussian Process Regression (GPR) was used
to generate the desired trajectory. User studies were also conducted to verify
the effectiveness of our proposed TIMS, comparing users' performance with and
without tactile feedback and/or haptic guidance.Comment: 8 pages, 7 figures. For more details of this project, please view our
website: https://sites.google.com/view/viewtims/hom
Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis
Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy
Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, we report an endovascular approach for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization was confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS) and histological analysis. The safety of the embolization therapy was assessed through biocompatibility evaluation and histopathology assays. Our strategy, seamlessly integrating secure drug packaging, agile magnetic actuation and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy
Flt3L-Mediated expansion of plasmacytoid dendritic cells suppresses HIV infection in humanized mice
Plasmacytoid dendritic cells (plasmacytoid DC, pDC)
are major IFN-I producers and have been shown to be
affected by HIV through ill-defined mechanisms. In
this study, we directly assess the role of pDC in early
infection, evaluating whether modulating their abundance can alter viral replication. First, HIV infection
of humanized mice induces systemic depletion of
pDC, and in the presence of soluble FMS-like tyrosine
kinase 3 ligand (Flt3L), pDC levels remain elevated.
Flt3L significantly delays the onset of viremia and reduces viral replication via a process that is dependent
on pDC and mediated through an enhanced early
IFN-I response. pDC from Flt3L-treated mice are
more prone to express IFN-a following TLR7 stimulation, but this propensity is gradually decreased during
infection. In conclusion, maintaining pDC levels and
function is key to effective early viral control, and in
this context, these findings provide practical insights
for anti-HIV strategies and vaccine design
Intestinal Microbiota-Derived GABA Mediates Interleukin-17 Expression during Enterotoxigenic Escherichia coli Infection
Intestinal microbiota has critical importance in pathogenesis of intestinal infection; however, the role of intestinal microbiota in intestinal immunity during enterotoxigenic Escherichia coli (ETEC) infection is poorly understood. The present study tested the hypothesis that the intestinal microbiota is associated with intestinal interleukin-17 (IL-17) expression in response to ETEC infection. Here, we found ETEC infection induced expression of intestinal IL-17 and dysbiosis of intestinal microbiota, increasing abundance of γ-aminobutyric acid (GABA)-producing Lactococcus lactis subsp. lactis. Antibiotics treatment in mice lowered the expression of intestinal IL-17 during ETEC infection, while GABA or L. lactis subsp. lactis administration restored the expression of intestinal IL-17. L. lactis subsp. lactis administration also promoted expression of intestinal IL-17 in germ-free mice during ETEC infection. GABA enhanced intestinal IL-17 expression in the context of ETEC infection through activating mechanistic target of rapamycin complex 1 (mTORC1)-ribosomal protein S6 kinase 1 (S6K1) signaling. GABA–mTORC1 signaling also affected intestinal IL-17 expression in response to Citrobacter rodentium infection and in drug-induced model of intestinal inflammation. These findings highlight the importance of intestinal GABA signaling in intestinal IL-17 expression during intestinal infection and indicate the potential of intestinal microbiota-GABA signaling in IL-17-associated intestinal diseases
KLRC1 knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors
IntroductionNatural Killer (NK) cells hold the potential to shift cell therapy from a complex autologous option to a universal off-the-shelf one. Although NK cells have demonstrated efficacy and safety in the treatment of leukemia, the limited efficacy of NK cell-based immunotherapies against solid tumors still represents a major hurdle. In the immunosuppressive tumor microenvironment (TME), inhibitory interactions between cancer and immune cells impair antitumoral immunity. KLRC1 gene encodes the NK cell inhibitory receptor NKG2A, which is a potent NK cell immune checkpoint. NKG2A specifically binds HLA-E, a non-classical HLA class I molecule frequently overexpressed in tumors, leading to the transmission of inhibitory signals that strongly impair NK cell function.MethodsTo restore NK cell cytotoxicity against HLA-E+ tumors, we have targeted the NKG2A/HLA-E immune checkpoint by using a CRISPR-mediated KLRC1 gene editing.ResultsKLRC1 knockout resulted in a reduction of 81% of NKG2A+ cell frequency in ex vivo expanded human NK cells post-cell sorting. In vitro, the overexpression of HLA-E by tumor cells significantly inhibited wild-type (WT) NK cell cytotoxicity with p-values ranging from 0.0071 to 0.0473 depending on tumor cell lines. In contrast, KLRC1KO NK cells exhibited significantly higher cytotoxicity when compared to WT NK cells against four different HLA-E+ solid tumor cell lines, with p-values ranging from<0.0001 to 0.0154. Interestingly, a proportion of 43.5% to 60.2% of NKG2A− NK cells within the edited NK cell population was sufficient to reverse at its maximum the HLA-E-mediated inhibition of NK cell cytotoxicity. The expression of the activating receptor NKG2C was increased in KLRC1KO NK cells and contributed to the improved NK cell cytotoxicity against HLA-E+ tumors. In vivo, the adoptive transfer of human KLRC1KO NK cells significantly delayed tumor progression and increased survival in a xenogeneic mouse model of HLA-E+ metastatic breast cancer, as compared to WT NK cells (p = 0.0015).ConclusionsOur results demonstrate that KLRC1 knockout is an effective strategy to improve NK cell antitumor activity against HLA-E+ tumors and could be applied in the development of NK cell therapy for solid tumors
Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes
Lis1-Nde1 integrates cerebral cortical neurogenesis with neuronal migration by stabilizing the basal-lateral surface of radial glial cells
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