Application of Intestinal Barrier Molecules in the Diagnosis of Acute Cellular Rejection After Intestinal Transplantation.

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.

CART Peptides Differently Regulate Firing Rates and GABAergic Synaptic Inputs of DMV Neurons Innervating the Stomach Antrum and Cecum of Adult Male Rats.

BACKGROUND/AIM: Central administration of cocaine- and amphetamine-regulated transcript peptides (CARTp) alters gastrointestinal motility and reduces food intake in rats. Since neurons in the dorsal motor nucleus of the vagus (DMV) receive GABAergic and glutamatergic inputs and innervate the smooth muscle of gastrointestinal organs, we hypothesized that CARTp acts on the DMV or presynaptic neurons. METHODS: We used 3,3'-dioctadecyloxa-carbocyanine perchlorate (DiO) retrograde tracing with electrophysiological methods to record DMV neurons innervating the stomach antrum or cecum in brainstem slices from adult rats. RESULTS: DiO application did not change the electrophysiological properties of DMV neurons. CART55-102 had no effect on the basal firing rates of neurons in either the stomach antrum-labeled group (SLG) or cecum-labeled group (CLG). When presynaptic inputs were blocked, CART55-102 further increased the firing rates of the SLG, suggesting a direct excitatory effect. Spontaneous inhibitory postsynaptic currents (sIPSCs) occurred at a higher frequency in SLG neurons than in CLG neurons. CART55-102 reduced the amplitude and the frequency of sIPSCs in SLG neurons dose-dependently, with higher doses also reducing spontaneous excitatory postsynaptic currents (sEPSCs). Higher doses of CART55-102 reduced sIPSC and sEPSC amplitudes in CLG neurons, suggesting a postsynaptic effect. In response to incremental current injections, the SLG neurons exhibited less increases in firing activity. Simultaneous applications of current injections and CART55-102 decreased the firing activity of the CLG. Therefore, stomach antrum-projecting DMV neurons possess a higher gating ability to stabilize firing activity. CONCLUSION: The mechanism by which CARTp mediates anorectic actions may be through a direct reduction in cecum-projecting DMV neuron excitability and, to a lesser extent, that of antrum-projecting DMV neurons, by acting on receptors of these neurons.

Impact of Metabolic Surgery on Gut Microbiota and Sera Metabolomic Patterns among Patients with Diabetes.

Metabolic surgery is a promising treatment for obese individuals with type 2 diabetes mellitus (T2DM), but the mechanism is not completely understood. Current understanding of the underlying ameliorative mechanisms relies on alterations in parameters related to the gastrointestinal hormones, biochemistry, energy absorption, the relative composition of the gut microbiota, and sera metabolites. A total of 13 patients with obesity and T2DM undergoing metabolic surgery treatments were recruited. Systematic changes of critical parameters and the effects and markers after metabolic surgery, in a longitudinal manner (before surgery and three, twelve, and twenty-four months after surgery) were measured. The metabolomics pattern, gut microbiota composition, together with the hormonal and biochemical characterizations, were analyzed. Body weight, body mass index, total cholesterol, triglyceride, fasting glucose level, C-peptide, HbA1c, HOMA-IR, gamma-glutamyltransferase, and des-acyl ghrelin were significantly reduced two years after metabolic surgery. These were closely associated with the changes of sera metabolomics and gut microbiota. Significant negative associations were found between the Eubacterium eligens group and lacosamide glucuronide, UDP-L-arabinose, lanceotoxin A, pipercyclobutanamide B, and hordatine B. Negative associations were identified between Ruminococcaceae UCG-003 and orotidine, and glucose. A positive correlation was found between Enterococcus and glutamic acid, and vindoline. Metabolic surgery showed positive effects on the amelioration of diabetes and metabolic syndromes, which were closely associated with the change of sera metabolomics, the gut microbiota, and other disease-related parameters.

Nutritional and dietary strategy in the clinical care of inflammatory bowel disease.

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Development of Novel Lightweight Dual-Phase Al-Ti-Cr-Mn-V Medium-Entropy Alloys with High Strength and Ductility.

A novel lightweight Al-Ti-Cr-Mn-V medium-entropy alloy (MEA) system was developed using a nonequiatiomic approach and alloys were produced through arc melting and drop casting. These alloys comprised a body-centered cubic (BCC) and face-centered cubic (FCC) dual phase with a density of approximately 4.5 g/cm3. However, the fraction of the BCC phase and morphology of the FCC phase can be controlled by incorporating other elements. The results of compression tests indicated that these Al-Ti-Cr-Mn-V alloys exhibited a prominent compression strength (~1940 MPa) and ductility (~30%). Moreover, homogenized samples maintained a high compression strength of 1900 MPa and similar ductility (30%). Due to the high specific compressive strength (0.433 GPa·g/cm3) and excellent combination of strength and ductility, the cast lightweight Al-Ti-Cr-Mn-V MEAs are a promising alloy system for application in transportation and energy industries.

A perspective on metabolic surgery from a gastroenterologist.

Type 2 diabetes (T2D) and obesity are important public health problems. The global prevalence of diabetes mellitus is 8.8%. Interventional diabetology and obesitology have been recently advocated as treatment options for T2D and obesity. The roles of metabolic surgery such as Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding, and biliopancreatic diversion are focused. Different types of metabolic surgeries have different glucose-lowering and weight loss effects. Endoscopic treatments include the intra-gastric balloon (to restrict the gastric volume) and duodenal-jejunal bypass liner (DJBL, as a malabsorptive procedure). Anatomic changes in the gastrointestinal tract may cause alterations in gut hormones, bile acids, adipokines, inflammatory cytokines, hepatokines, myokines, gut microbiota, and even unidentified factors. Modulating gut hormones, including foregut (ghrelin, glucose-dependent insulinotropic polypeptide) and hindgut (glucagon-like peptide-1, peptide YY) hormones, through metabolic surgeries improves glycemic homeostasis. Metabolic surgeries reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines. Metabolic surgeries also regulate one's appetite through the new establishment of jejunal nutrient sensing. Therefore, the effects of metabolic surgery and DJBL implantation emphasize the crucial role of the small intestine in glucose homeostasis. Removing diabetogenic or obesogenic factors from the duodenum and/or jejunum may help to solve the problems of diabetes and obesity in the future.

Solution Processable Holey Graphene Oxide and Its Derived Macrostructures for High-Performance Supercapacitors.

Scalable preparation of solution processable graphene and its bulk materials with high specific surface areas and designed porosities is essential for many practical applications. Herein, we report a scalable approach to produce aqueous dispersions of holey graphene oxide with abundant in-plane nanopores via a convenient mild defect-etching reaction and demonstrate that the holey graphene oxide can function as a versatile building block for the assembly of macrostructures including holey graphene hydrogels with a three-dimensional hierarchical porosity and holey graphene papers with a compact but porous layered structure. These holey graphene macrostructures exhibit significantly improved specific surface area and ion diffusion rate compared to the nonholey counterparts and can be directly used as binder-free supercapacitor electrodes with ultrahigh specific capacitances of 283 F/g and 234 F/cm(3), excellent rate capabilities, and superior cycling stabilities. Our study defines a scalable pathway to solution processable holey graphene materials and will greatly impact the applications of graphene in diverse technological areas.

From endocrine to rheumatism: do gut hormones play roles in rheumatoid arthritis?

RA is characterized by chronic inflammation in the musculoskeletal system, in which TNF-α is the key cytokine trigger. TNF-α, previously known as cachectin, is implicated in the modulation of body composition and energy expenditure. Gut hormones, including acyl ghrelin, des-acyl ghrelin, GIP, GLP-1 and PYY, have been known to be the major regulators of appetite, nutrition, energy expenditure and body mass formation. Emerging evidence indicates that blockade of TNF-α by biologics not only ameliorates rheumatoid inflammation, but can affect the secretion and action of gut hormones on appetite, body composition, energy expenditure, muscle catabolism and bone remodelling. A link between the gastrointestinal endocrine axis and the immune system may be established through the interaction of proinflammatory cytokines, including TNF-α and these gut hormones. With the ever-increasing understanding of rheumatoid inflammation and the invention of more biologics to modulate the cytokine network, more attention should be given to the possible immunomodulatory roles of gut hormones in autoimmune inflammatory reactions.

Independent variations of applied voltage and injection current for controlling the quantum-confined Stark effect in an InGaN/GaN quantum-well light-emitting diode.

A reverse-biased voltage is applied to either device in the vertical configuration of two light-emitting diodes (LEDs) grown on patterned and flat Si (110) substrates with weak and strong quantum-confined Stark effects (QCSEs), respectively, in the InGaN/GaN quantum wells for independently controlling the applied voltage across and the injection current into the p-i-n junction in the lateral configuration of LED operation. The results show that more carrier supply is needed in the LED of weaker QCSE to produce a carrier screening effect for balancing the potential tilt in increasing the forward-biased voltage, when compared with the LED of stronger QCSE. The small spectral shift range in increasing injection current in the LED of weaker QCSE is attributed not only to the weaker QCSE, but also to its smaller device resistance such that a given increment of applied voltage leads to a larger increment of injection current. From a viewpoint of practical application in LED operation, by applying a reverse-biased voltage in the vertical configuration, the applied voltage and injection current in the lateral configuration can be independently controlled by adjusting the vertical voltage for keeping the emission spectral peak fixed.

Impacts of Central Administration of the Novel Peptide, LEAP-2, in Different Food Intake Models in Conscious Rats.

Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of O-n-octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics.

Enhancing the Strength and Ductility Synergy of Lightweight Ti-Rich Medium-Entropy Alloys through Ni Microalloying.

Medium-entropy alloys (MEAs) have attracted considerable attention in recent decades due to their exceptional material properties and design flexibility. In this study, lightweight and non-equiatomic MEAs with low density (~5 g/cm3), high strength (yield strength: 1200 MPa), and high ductility (plastic deformation: ≧10%) were explored. We fine-tuned a previously developed Ti-rich MEA by microalloying it with small amounts of Ni (reducing the atomic radius and increasing the elastic modulus) through solid solution strengthening to achieve a series of MEAs with enhanced mechanical properties. Among the prepared MEAs, Ti65Ni1 and Ti65Ni3 exhibited optimal properties in terms of the balance between strength and ductility. Furthermore, the Ti65Ni3 MEA was subjected to thermo-mechanical treatment (TMT) followed by cold rolling 70% (CR70) and cold rolling 85% (CR85). Subsequently, the processed samples were rapidly annealed at 743 °C, 770 °C, 817 °C, and 889 °C at a heating rate of 15 °C/s. X-ray diffraction analysis revealed that the MEA could retain its single-body-centered cubic solid solution structure after TMT. Additionally, the tensile testing results revealed that increasing the annealing temperature led to a decrease in yield strength and an increase in ductility. Notably, the Ti65Ni3 MEA sample that was subjected to CR70 and CR85 processing and annealed for 30 s exhibited high yield strength (>1250 MPa) and ductility (>13%). In particular, the Ti65Ni3 MEA subjected to CR85 exhibited a specific yield strength of 264 MPa·cm3/g, specific tensile strength of 300 MPa·cm3/g, and ductility of >13%.

Vertical light-emitting diodes with surface gratings and rough surfaces for effective light extraction.

For enhancing the light extraction of a light-emitting diode, surface grating fabrication based on a simple method of combining photoelectrochemical (PEC) etching with phase mask interferometry has been demonstrated. To understand the optimum grating period in forming a surface grating on a vertical light-emitting diode (VLED), we construct a Llyod's interferometer within PEC electrolyte (KOH) to fabricate surface gratings of various periods on VLEDs for comparing their light extraction efficiencies. Also, to compare the effectiveness of light extraction enhancement between surface grating and rough surface, VLEDs with the rough surfaces fabricated with two different KOH wet etching methods are fabricated. The comparisons of VLED characterizations show that among those grating VLEDs, the light extraction is more effective in a VLED of a smaller grating period. Also, compared with VLEDs of rough surfaces, the grating VLEDs of short grating periods (<2 µm) have the higher light extraction efficiencies, even though the root-mean-square roughness of the rough surface is significantly larger than the grating groove depth.

Triboelectric-generator-driven pulse electrodeposition for micropatterning.

By converting ambient energy into electricity, energy harvesting is capable of at least offsetting, or even replacing, the reliance of small portable electronics on traditional power supplies, such as batteries. Here we demonstrate a novel and simple generator with extremely low cost for efficiently harvesting mechanical energy that is typically present in the form of vibrations and random displacements/deformation. Owing to the coupling of contact charging and electrostatic induction, electric generation was achieved with a cycled process of contact and separation between two polymer films. A detailed theory is developed for understanding the proposed mechanism. The instantaneous electric power density reached as high as 31.2 mW/cm(3) at a maximum open circuit voltage of 110 V. Furthermore, the generator was successfully used without electric storage as a direct power source for pulse electrodeposition (PED) of micro/nanocrystalline silver structure. The cathodic current efficiency reached up to 86.6%. Not only does this work present a new type of generator that is featured by simple fabrication, large electric output, excellent robustness, and extremely low cost, but also extends the application of energy-harvesting technology to the field of electrochemistry with further utilizations including, but not limited to, pollutant degradation, corrosion protection, and water splitting.

Coaxial metal-silicide Ni2Si/C54-TiSi2 nanowires.

One-dimensional metal silicide nanowires are excellent candidates for interconnect and contact materials in future integrated circuits devices. Novel core-shell Ni(2)Si/C54-TiSi(2) nanowires, 2 µm in length, were grown controllably via a solid-liquid-solid growth mechanism. Their interesting ferromagnetic behaviors and excellent electrical properties have been studied in detail. The coercivities (Hcs) of the core-shell Ni(2)Si/C54-TiSi(2) nanowires was determined to be 200 and 50 Oe at 4 and 300 K, respectively, and the resistivity was measured to be as low as 31 µΩ-cm. The shift of the hysteresis loop with the temperature in zero field cooled (ZFC) and field cooled (FC) studies was found. ZFC and FC curves converge near room temperature at 314 K. The favorable ferromagnetic and electrical properties indicate that the unique core-shell nanowires can be used in penetrative ferromagnetic devices at room temperature simultaneously as a future interconnection in integrated circuits.

Self-Enhancement of Water Electrolysis by Electrolyte-Poled Ferroelectric Catalyst.

Efficient and durable electrocatalysts with superior activity are needed for the production of green hydrogen with a high yield and low energy consumption. Electrocatalysts based on transition metal oxides hold dominance due to their abundant natural resources, regulable physical properties, and good adaptation to a solution. In numerous oxide catalyst materials, ferroelectrics, possessing semiconducting characteristics and switchable spontaneous polarization, have been considered promising photoelectrodes for solar water splitting. However, few investigations noted their potential as electrocatalysts. In this study, we report an efficient electrocatalytic electrode made of a BiFeO3/nickel foam heterostructure, which displays a smaller overpotential and higher current density than the blank nickel foam electrode. Moreover, when in contact with an alkaline solution, the bond between hydroxyls and the BiFeO3 surface induces a large area of upward self-polarization, lowering the adsorption energy of subsequent adsorbates and facilitating oxygen and hydrogen evolution reaction. Our work demonstrates an infrequent pathway of using functional semiconducting materials for exploiting highly efficient electrocatalytic electrodes.

Emergent ferromagnetism with superconductivity in Fe(Te,Se) van der Waals Josephson junctions.

Ferromagnetism and superconductivity are two key ingredients for topological superconductors, which can serve as building blocks of fault-tolerant quantum computers. Adversely, ferromagnetism and superconductivity are typically also two hostile orderings competing to align spins in different configurations, and thus making the material design and experimental implementation extremely challenging. A single material platform with concurrent ferromagnetism and superconductivity is actively pursued. In this paper, we fabricate van der Waals Josephson junctions made with iron-based superconductor Fe(Te,Se), and report the global device-level transport signatures of interfacial ferromagnetism emerging with superconducting states for the first time. Magnetic hysteresis in the junction resistance is observed only below the superconducting critical temperature, suggesting an inherent correlation between ferromagnetic and superconducting order parameters. The 0-π phase mixing in the Fraunhofer patterns pinpoints the ferromagnetism on the junction interface. More importantly, a stochastic field-free superconducting diode effect was observed in Josephson junction devices, with a significant diode efficiency up to 10%, which unambiguously confirms the spontaneous time-reversal symmetry breaking. Our work demonstrates a new way to search for topological superconductivity in iron-based superconductors for future high Tc fault-tolerant qubit implementations from a device perspective.

Comparison of emission characteristics between the CdZnO/ZnO quantum wells on ZnO and GaN templates.

CdZnO/ZnO quantum well (QW) samples are grown on GaN and ZnO templates with plasma-assisted molecular beam epitaxy under different conditions of substrate temperature, Cd effusion cell temperature, and O(2) flow rate for emission characteristics comparison. It is found that the Cd incorporation on the ZnO template is generally lower, when compared with that on the GaN template, such that the O(2) flow rate needs to be reduced for stoichiometric CdZnO/ZnO QW growth on the ZnO template. Besides the wurtzite (wt) CdZnO structure, the rock-salt (rs) CdZnO structure exists in the CdZnO well layers when the total Cd content is high. The rs structure may dominate over the wt structure in photoluminescence intensity when the total Cd content is high. In either group of samples on the GaN and ZnO templates, the emission efficiency first increases and then decreases with increasing total Cd content. The low emission efficiency at low (high) Cd content is attributed to the weaker quantum confinement (the poorer crystal quality) of the QWs. The emission efficiencies of the QW samples on the GaN template are generally higher than those on the ZnO template. The carrier localization behavior in a CdZnO/ZnO QW, grown on either GaN or ZnO template, is significantly weaker than that in an InGaN/GaN QW. The strength of the quantum-confined Stark effect generally increases with increasing Cd content in either group of samples on the GaN and ZnO templates.

Geometry and composition comparisons between c-plane disc-like and m-plane core-shell InGaN/GaN quantum wells in a nitride nanorod.

With the nano-imprint lithography and the pulsed growth mode of metalorganic chemical vapor deposition, a regularly-patterned, c-axis nitride nanorod (NR) array of quite uniform geometry with simultaneous depositions of top-face, c-plane disc-like and sidewall, m-plane core-shell InGaN/GaN quantum well (QW) structures is formed. The differences of geometry and composition between these two groups of QW are studied with scanning electron microscopy, cathodoluminescence, and transmission electron microscopy (TEM). In particular, the strain state analysis results in TEM observations provide us with the information about the QW width and composition. It is found that the QW widths are narrower and the indium contents are higher in the sidewall m-plane QWs, when compared with the top-face c-plane QWs. Also, in the sidewall m-plane QWs, the QW width (indium content) decreases (increases) with the height on the sidewall. The observed results can be interpreted with the migration behaviors of the constituent atoms along the NR sidewall from the bottom.

Effects of overgrown p-layer on the emission characteristics of the InGaN/GaN quantum wells in a high-indium light-emitting diode.

The counteraction between the increased carrier localization effect due to the change of composition nanostructure in the quantum wells (QWs), which is caused by the thermal annealing process, and the enhanced quantum-confined Stark effect in the QWs due to the increased piezoelectric field, which is caused by the increased p-type layer thickness, when the p-type layer is grown at a high temperature on the InGaN/GaN QWs of a high-indium light-emitting diode (LED) is demonstrated. Temperature- and excitation power-dependent photoluminescence (PL) measurements are performed on three groups of sample, including 1) the samples with both effects of thermal annealing and increased p-type thickness, 2) those only with the similar thermal annealing process, and 3) those with increased overgrowth thickness and minimized thermal annealing effect. From the comparisons of emission wavelength, internal quantum efficiency (IQE), spectral shift with increasing PL excitation level, and calibrated activation energy of carrier localization between various samples in the three groups, one can clearly see the individual effects of thermal annealing and increased p-type layer thickness. The counteraction leads to increased IQE and blue-shifted emission spectrum with increasing p-type thickness when the thickness is below a certain value (20-nm p-AlGaN plus 60-nm p-GaN under our growth conditions). Beyond this thickness, the IQE value decreases and the emission spectrum red shifts with increasing p-type thickness.