Novel miniature transendoscopic telerobotic system for endoscopic submucosal dissection (with videos).

BACKGROUND AND AIMS: The lack of tissue traction and instrument dexterity to allow for adequate visualization and effective dissection were the main issues in performing endoscopic submucosal dissection (ESD). Robot-assisted systems may provide advantages. In this study we developed a novel transendoscopic telerobotic system and evaluated its performance in ESD. METHODS: A miniature dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) was developed. The DREAMS system contained the current smallest robotic ESD instruments and was compatible with the commercially available dual-channel endoscope. After the system was established, a prospective randomized controlled study was conducted to validate the performance of the DREAMS-assisted ESD in terms of efficacy, safety, and workload by comparing it with the conventional technique. RESULTS: Two robotic instruments can achieve safe collaboration and provide sufficient visualization and efficient dissection during ESD. Forty ESDs in the stomach and esophagus of 8 pigs were completed by DREAMS-assisted ESD or conventional ESD. Submucosal dissection time was comparable between the 2 techniques, but DREAMS-assisted ESD demonstrated a significantly lower muscular injury rate (15% vs 50%, P = .018) and workload scores (22.30 vs 32.45, P < .001). In the subgroup analysis of esophageal ESD, DREAMS-assisted ESD showed significantly improved submucosal dissection time (6.45 vs 16.37 minutes, P = .002), muscular injury rate (25% vs 87.5%, P = .041), and workload (21.13 vs 40.63, P = .001). CONCLUSIONS: We developed a novel transendoscopic telerobotic system, named DREAMS. The safety profile and technical feasibility of ESD were significantly improved with the assistance of the DREAMS system, especially in the narrower esophageal lumen.

Excessive Mitochondrial Fission Suppresses Mucosal Repair by Impairing Butyrate Metabolism in Colonocytes.

BACKGROUND: Mucosal healing is one of the principal therapeutic targets for ulcerative colitis (UC). Mitochondria are dynamic organelles that undergo constant fusion and fission; however, the process that is most conducive to mucosal healing remains unclear. This study investigated the role of mitochondrial fission in mucosal healing in UC patients. METHODS: Quantitative polymerase chain reaction, Western blotting, and immunostaining were used to detect mitochondrial fission in UC patients and a dextran sulfate sodium-induced colitis model. Colonic organoids were used to investigate the role of mitochondrial fission in butyrate metabolism. Enzyme activity assays were performed to identify the key proteins involved in this mechanism. RESULTS: It was found that inhibition of mitochondrial fission promoted mucosal healing in mice and that there was an increase in mitochondrial fission in colonic epithelial cells of UC patients. Excessive fission inhibits stem cell proliferation by impairing butyrate metabolism in colonic organoids. The mitochondrial fission antagonist P110 failed to promote mucosal healing in antibiotic-treated mice, and the addition of exogenous butyrate reversed this effect. Increased butyrate exposure in the colonic stem cell niche has also been observed in UC patients. Mechanistically, enzyme activity assays on colonic organoids revealed that excessive fission inhibits mitochondrial acetoacetyl-CoA thiolase activity via reactive oxygen species. CONCLUSIONS: Collectively, these data indicate that excessive mitochondrial fission suppresses mucosal repair by inhibiting butyrate metabolism and provides a potential target for mucosal healing in patients with ulcerative colitis.

Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis.

Piezo1, the mechanosensory ion channel, has attracted increasing attention for its essential roles in various inflammatory responses and immune-related diseases. Although most of the key immune cells in inflammatory bowel disease (IBD) have been reported to be regulated by Piezo1, the specific role of Piezo1 in colitis has yet to be intensively studied. The present study investigated the impact of pharmacological inhibition of Piezo1 on dextran sulfate sodium (DSS)-induced colitis and explored the role of Piezo1 in intestinal immune cells in the context of colitis. We observed upregulated expression of Piezo1 in the colon tissue of mice with DSS-induced colitis. Pharmacological inhibition of Piezo1 by GsMTx4 diminished the severity of colitis. Piezo1 inhibition downregulated the expression of pro-inflammatory mediators Il1b, Il6, and Ptgs2 in colonic tissue and suppressed the production of IL-6 from macrophages and dendritic cells without altering the balance of T helper (Th) cells. In particular, Piezo1 did not affect cell viability but regulated cell proliferation and production of IL-17A in group 3 innate lymphoid cells (ILC3s), which is dependent on the PI3K-Akt-mTOR signaling pathway. Our findings uncover Piezo1 as an effective regulator of gut inflammation. Targeting Piezo1 could be a promising strategy to modulate intestinal immunity in IBD.

miR-122-5p Restrains Pancreatic Cancer Cell Growth and Causes Apoptosis by Negatively Regulating ASCT2.

BACKGROUND/AIM: System ASC amino acid transporter-2 (ASCT2) is abnormally highly expressed in tumor cells and closely associated with a poor prognosis, but the regulatory mechanism of abnormally high ASCT2 expression is scarcely investigated. MicroRNAs (miRNAs) that are abnormally expressed regulate gene expression to have either oncogenic or tumor-suppressive effects in pancreatic cancer (PC). MicroRNA-122-5p (miR-122-5p) dysregulation has been seen in various cancer entities, but the biological function of miR-122-5p in PC and its regulation mechanisms remain unknown. MATERIALS AND METHODS: Western blot and quantitative RT-PCR were used to measure the expression of miR-122-5p, ASCT2, and apoptosis-related proteins. CCK-8 assays were used to elucidate the effect on cell proliferation. Flow cytometry (FCM) assays were utilized to evaluate cell apoptosis. A dual-luciferase reporter assay was utilized to determine if miR-122a-5p directly targeted ASCT2. Glutamine consumption and the α-ketoglutarate (α-KG) and adenosine triphosphate (ATP) contents were determined using respective assays. RESULTS: MiR-122-5p expression was low whereas ASCT2 expression was high in PC tissues and cells. Overexpressing miR-122-5p restrained pancreatic cancer cell proliferation, accelerated apoptosis, and decreased glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation, whereas suppressing miR-122-5p had the opposite effect. Moreover, the reporter gene test established ASCT2 as a miR-122-5p target. Overexpression of miR-122-5p decreased ASCT2 expression, whereas miR-122-5p repression increased ASCT2 expression. In addition, miR-122-5p also regulated apoptosis-related pathways. CONCLUSION: MiR-122-5p may function as a tumor suppressor by inhibiting the proliferation, glutamine metabolism, and inducing apoptosis via altering the expression of ASCT2 in pancreatic cancer cells.

Robot-assisted endoscopic submucosal dissection contributes to efficient and safe learning for novices: Prospective pilot cross-over ex vivo study (with video).

OBJECTIVES: The lack of effective countertraction to expose the submucosal layer contributes to the technical complication and adverse events in endoscopic submucosal dissection (ESD). We aimed to evaluate the efficacy and safety of a novel endoscopic robot (flexible auxiliary single-arm transluminal endoscopic robot [FASTER]) for ESD learning for novices. METHODS: This was a prospective, cross-over designed pilot study in ex vivo porcine stomach. Four ESD novices were randomized to either FASTER-assisted ESD first (FC) group or a conventional ESD first (CF) group, performed 40 gastric ESDs using each technique, then crossed over to another technique. The performance and learning curve were compared between the two groups. RESULTS: In the first phase, novices in the FC group demonstrated significantly better performance with shorter procedure time (25.6 ± 7.8 vs. 38.9 ± 13.4 min; P < 0.001) and submucosal dissection time (13.9 ± 5.5 vs. 23.1 ± 11.0 min; P < 0.001), higher direct-vision dissection ratio (84.0 ± 7.9% vs. 43.5 ± 20.7%; P < 0.001), and lower muscular injury (2.5 vs. 40.0%; P < 0.001) and task load (4 vs. 5; P < 0.001). Fewer ESDs were required to gain early proficiency in the FC group. When crossed to the second phase, procedure time in the FC group was prolonged but the muscular injury rate did not increase significantly. In total, endoscopists in the FC group tended to have a lower task load (4 vs. 5; P = 0.008) and less muscular injury (10.0 vs. 21.3%; P = 0.05). CONCLUSION: Flexible auxiliary single-arm transluminal endoscopic robot-assisted learning reduces the technical difficulty of ESD for novices and the safety profile can sustain in following conventional ESD. These results indicated that FASTER has potential implications for ESD training in clinical practice.

A novel flexible auxiliary single-arm transluminal endoscopic robot facilitates endoscopic submucosal dissection of gastric lesions (with video).

BACKGROUND: Using conventional endoscope to perform endoscopic submucosal dissection (ESD) is difficult because of the one-handed operation and blind dissection caused by gravity. Poor visualization of the submucosal plane causes ESD to be associated with a high risk of bleeding and perforation. This study aimed to develop a novel ESD-assistive robot system and to evaluate its efficacy. METHODS: A novel flexible auxiliary single-arm transluminal endoscopic robot (FASTER) was developed. A total of 36 artificial lesions in ex vivo porcine stomachs were removed using the FASTER-assisted ESD method (n = 18) and the conventional ESD method (n = 18). Lesions were 2 cm or 4 cm in diameter, located on the anterior and posterior walls of the antrum. Primary outcome measurements were dissection time and dissection speed. RESULTS: The dissection time in FASTER-assisted ESD was significantly shorter than that in conventional ESD (7 min vs 13 min, p = 0.012), mainly because of the faster dissection speed (148.6 vs 97.0 mm2/min, p = 0.002). The total procedure time in FASTER-assisted ESD was shorter than that in conventional ESD, but the difference was not significant (16 min vs 24 min, p = 0.252). Complete en bloc resection was achieved in all lesions. No perforations were detected. The FASTER exhibited the ability of regrasp, multidirectional traction, and proper tension control during ESD. CONCLUSION: FASTER significantly increased the dissection speed by providing proper traction and achieving good submucosal vision. This new device is expected to facilitate ESD in clinical practice.

Simplified robot-assisted endoscopic submucosal dissection for esophageal and gastric lesions: a randomized controlled porcine study (with videos).

BACKGROUND AND AIMS: Effective countertraction is a main challenging issue in endoscopic submucosal dissection (ESD). Several countertraction methods have been developed to address this issue. The aim of this study was to compare the efficacy of ESD using a novel simplified robot, the flexible auxiliary single-arm transluminal endoscopic robot (FASTER), with a traditional technique. METHODS: This was a prospective, randomized animal study. Forty-eight ESDs in 6 pigs were carried out at 8 different locations (gastric antrum, gastric body, lower esophagus, and middle esophagus) by the conventional method (n = 24) and by the FASTER-assisted method (n = 24). The primary outcomes were total procedure time, dissection time, and rate of direct-vision dissection. Secondary endpoints were completeness of en-bloc resection and adverse event rate. RESULTS: The total procedure time was significantly shorter in FASTER-assisted ESD than in conventional ESD (18.8 vs 32.8 minutes; P < .001). In contrast to the median direct-vision dissection rate of 73% with conventional ESD, the FASTER-assisted group had a significantly higher rate of 96% (P < .001). The number of sites of muscular damage was significantly lower using the FASTER-assisted method than the conventional method (6 vs 21, respectively; P = .018). This improvement was more apparent in esophageal lesions compared with gastric lesions. CONCLUSIONS: This study demonstrated that using a simplified robot during ESD is technically feasible and enables the endoscopist to dynamically use countertraction. This device could significantly reduce procedure time compared with conventional ESD techniques.

Probiotic Interventions Alleviate Food Allergy Symptoms Correlated With Cesarean Section: A Murine Model.

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.

Complete genome sequencing of Peyer's patches-derived Lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity.

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.

The effects of substitutional Fe-doping on magnetism in MoS2and WS2monolayers.

Doping of two-dimensional (2D) semiconductors has been intensively studied toward modulating their electrical, optical, and magnetic properties. While ferromagnetic 2D semiconductors hold promise for future spintronics and valleytronics, the origin of ferromagnetism in 2D materials remains unclear. Here, we show that substitutional Fe-doping of MoS2and WS2monolayers induce different magnetic properties. The Fe-doped monolayers are directly synthesized via chemical vapor deposition. In both cases, Fe substitutional doping is successfully achieved, as confirmed using scanning transmission electron microscopy. While both Fe:MoS2and Fe:WS2show PL quenching and n-type doping, Fe dopants in WS2monolayers are found to assume deep-level trap states, in contrast to the case of Fe:MoS2, where the states are found to be shallow. Usingµm- and mm-precision local NV-magnetometry and superconducting quantum interference device, we discover that, unlike MoS2monolayers, WS2monolayers do not show a magnetic phase transition to ferromagnetism upon Fe-doping. The absence of ferromagnetism in Fe:WS2is corroborated using density functional theory calculations.

Enabling room temperature ferromagnetism in monolayer MoS2 via in situ iron-doping.

Two-dimensional semiconductors, including transition metal dichalcogenides, are of interest in electronics and photonics but remain nonmagnetic in their intrinsic form. Previous efforts to form two-dimensional dilute magnetic semiconductors utilized extrinsic doping techniques or bulk crystal growth, detrimentally affecting uniformity, scalability, or Curie temperature. Here, we demonstrate an in situ substitutional doping of Fe atoms into MoS2 monolayers in the chemical vapor deposition growth. The iron atoms substitute molybdenum sites in MoS2 crystals, as confirmed by transmission electron microscopy and Raman signatures. We uncover an Fe-related spectral transition of Fe:MoS2 monolayers that appears at 2.28 eV above the pristine bandgap and displays pronounced ferromagnetic hysteresis. The microscopic origin is further corroborated by density functional theory calculations of dipole-allowed transitions in Fe:MoS2. Using spatially integrating magnetization measurements and spatially resolving nitrogen-vacancy center magnetometry, we show that Fe:MoS2 monolayers remain magnetized even at ambient conditions, manifesting ferromagnetism at room temperature.

A stretchable and bendable all-solid-state pseudocapacitor with dodecylbenzenesulfonate-doped polypyrrole-coated vertically aligned carbon nanotubes partially embedded in PDMS.

We present an all-solid-state flexible and stretchable pseudocapacitor composed of dodecylbenzenesulfonate-doped polypyrrole (PPy(DBS))-coated vertically aligned carbon nanotubes (VACNTs) partially embedded in a polydimethylsiloxane (PDMS) substrate. VACNTs are grown via atmospheric-pressure chemical vapor deposition on a Si/SiO2 substrate and transferred onto PDMS. Then, the PPy(DBS) film is coated with a surface charge of 300 mC cm-2 on individual carbon nanotubes (CNTs) via electropolymerization. The partial embedment of VACNTs in PDMS permits a rapid and facile integration of the PPy(DBS)/CNTs/PDMS structure to construct a flexible and stretchable supercapacitor electrode. The measured capacitance is 3.6 mF cm-2 with a PVA-KOH gel electrolyte at a scan rate of 100 mV s-1, which is maintained under stretching from 0% to 150% and bending/twisting angles from 0° to 180°. This all-solid-state stretchable supercapacitor shows a stable galvanostatic performance during 10 000 charge/discharge cycles with its capacitance retained at 109%.

A carbon nanotube-embedded conjugated polymer mesh with controlled oil absorption and surface regeneration via in situ wettability switch.

This paper presents a mesh-type absorbent made of a carbon nanotube (CNT)-embedded polypyrrole dodecylbenzenesulfonate (PPy(DBS)) surface for controlled absorption and release of oils and regeneration of polymer surfaces toward continuous oil/water separation. The mesh absorbs dichloromethane (DCM) under oxidation in aqueous environment and releases them under reduction via in situ switching of underwater wettability. CNTs were grown out of stainless steel surfaces and embedded into the PPy(DBS) film, which enhanced the switchable wettability as well as the surface regeneration. The CNT-embedded morphology improved oil retention by a factor of two in an oxidized state and decreased wettability switch time by 16% in a reduced state over the mesh without CNT embedment during 250 redox cyclic testing. A rolled 2 cm × 3 cm CNT-embedded PPy(DBS) mesh was furthermore used to demonstrate the continuous absorption and release of oils, during which DCM of 16 times of the absorbent weight was collected in 50 redox cycles.

Graphene-vertically aligned carbon nanotube hybrid on PDMS as stretchable electrodes.

Stretchable electrodes are a critical component for flexible electronics such as displays, energy devices, and wearable sensors. Carbon nanotubes (CNTs) and graphene have been considered for flexible electrode applications, due to their mechanical strength, high carrier mobility, and excellent thermal conductivity. Vertically aligned carbon nanotubes (VACNTs) provide the possibility to serve as interconnects to graphene sheets as stretchable electrodes that could maintain high electrical conductivity under large tensile strain. In this work, a graphene oxide (GO)-VACNT hybrid on a PDMS substrate was demonstrated. Here, 50 µm long VACNTs were grown on a Si/SiO2 wafer substrate via atmospheric pressure chemical vapor deposition. VACNTs were directly transferred by delamination from the Si/SiO2 to a semi-cured PDMS substrate, ensuring strong adhesion between VACNTs and PDMS upon full curing of the PDMS. GO ink was then printed on the surface of the VACNT carpet and thermally reduced to reduced graphene oxide (rGO). The sheet resistance of the rGO-VACNT hybrid was measured under uniaxial tensile strains up to 300% applied to the substrate. Under applied strain, the rGO-VACNT hybrid maintained a sheet resistant of 386 ± 55 Ω/sq. Cyclic stretching of the rGO-VACNT hybrid was performed with up to 50 cycles at 100% maximum tensile strain, showing no increase in sheet resistance. These results demonstrate promising performance of the rGO-VACNT hybrid for flexible electronics applications.

Graphene-Assisted Antioxidation of Tungsten Disulfide Monolayers: Substrate and Electric-Field Effect.

Transition metal dichalcogenides (TMDs) have emerged as promising materials to complement graphene for advanced optoelectronics. However, irreversible degradation of chemical vapor deposition-grown monolayer TMDs via oxidation under ambient conditions limits applications of TMD-based devices. Here, the growth of oxidation-resistant tungsten disulfide (WS2 ) monolayers on graphene is demonstrated, and the mechanism of oxidation of WS2 on SiO2 , graphene/SiO2 , and on graphene suspended in air is elucidated. While WS2 on a SiO2 substrate begins oxidation within weeks, epitaxially grown WS2 on suspended graphene does not show any sign of oxidation, attributed to the screening effect of surface electric field caused by the substrate. The control of a local oxidation of WS2 on a SiO2 substrate by a local electric field created using an atomic force microscope tip is also demonstrated.

Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats.

The purpose of this study was to evaluate the effect of grape seed procyanidin (GSPE) fractions with different degrees of polymerisation (DPs) on blood glucose, lipids and hepatic oxidative stress in diabetic rats. Diabetic rats received a daily oral supplement of GSPE with different DPs for 6 weeks. During this period, blood glucose, body weight and food intake were assessed weekly. At the end of the experiment, serum lipid and hepatic oxidative stress were assessed compared with those of rats that did not receive GSPE. GSPE significantly decreased blood glucose, serum lipids and hepatic oxidative stress. Moreover, these effects were significantly better in the groups administered the oligomeric rather than the polymeric forms. These results demonstrate that GSPE has a positive effect on diabetes in rats, and the oligomeric form of GSPE may be more protective than other forms.