CD73-generated extracellular adenosine promotes resolution of neutrophil-mediated tissue injury and restrains metaplasia in pancreatitis.

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto-5'-nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73-/- ) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein-induced acute and chronic pancreatitis. In response to caerulein-mediated chronic or acute pancreatitis, WT mice display resolution of pancreatitis at earlier timepoints than CD73-/- mice. Using immunohistochemistry and analysis of single-cell RNA-seq (scRNA-seq) data, we determined CD73 localization in chronic pancreatitis is primarily observed in mucin/ductal cell populations and immune cells. In murine pancreata challenged with caerulein to induce acute pancreatitis, we compared CD73-/- to WT mice and observed a significant infiltration of Ly6G+, MPO+, and Granzyme B+ cells in CD73-/- compared to WT pancreata and we quantified a significant increase in acinar-to-ductal metaplasia demonstrating sustained metaplasia and inflammation in CD73-/- mice. Using neutrophil depletion in CD73-/- mice, we show neutrophil depletion significantly reduces metaplasia defined by CK19+ cells per field and significantly reduces acute pancreatitis. These data identify CD73 enhancers as a potential therapeutic strategy for patients with acute and chronic pancreatitis as adenosine generation and activation of adenosine receptors is critical to resolve persistent inflammation in the pancreas.

Formation of Supernarrow Borophene Nanoribbons.

Borophenes have sparked considerable interest owing to their fascinating physical characteristics and diverse polymorphism. However, borophene nanoribbons (BNRs) with widths less than 2 nm have not been achieved. Herein, we report the experimental realization of supernarrow BNRs. Combining scanning tunneling microscopy imaging with density functional theory modeling and ab initio molecular dynamics simulations, we demonstrate that, under the applied growth conditions, boron atoms can penetrate the outermost layer of Au(111) and form BNRs composed of a pair of zigzag (2,2) boron rows. The BNRs have a width self-contained to ∼1 nm and dipoles at the edges to keep them separated. They are embedded in the outermost Au layer and shielded on top by the evacuated Au atoms, free of the need for post-passivation. Scanning tunneling spectroscopy reveals distinct edge states, primarily attributed to the localized spin at the BNRs' zigzag edges. This work adds a new member to the boron material family and introduces a new physical feature to borophenes.

Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury.

BACKGROUND & AIMS: Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression. METHODS: Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by immunostaining. RESULTS: scRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with KrasG12D-induced ADM identifies populations associated with disease progression. Activation of KrasG12D expression in HNF1B+ or POU2F3+ ADM populations leads to neoplastic transformation and formation of MUC5AC+ gastric-pit-like cells. Human pancreatitis samples also harbor pyloric metaplasia with a similar transcriptional phenotype. CONCLUSIONS: Under conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. KrasG12D expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations and offers an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, providing insight into early events in pancreas diseases.

Mycorrhizal symbiosis reprograms ion fluxes and fatty acid metabolism in wild jujube during salt stress.

Chinese jujube (Ziziphus jujuba) is an important fruit tree in China, and soil salinity is the main constraint affecting jujube production. It is unclear how arbuscular mycorrhizal (AM) symbiosis supports jujube adaptation to salt stress. Herein, we performed comparative physiological, ion flux, fatty acid (FA) metabolomic, and transcriptomic analyses to examine the mechanism of AM jujube responding to salt stress. AM seedlings showed better performance during salt stress. AM symbiosis altered phytohormonal levels: indole-3-acetic acid and abscisic acid contents were significantly increased in AM roots and reduced by salt stress. Mycorrhizal colonization enhanced root H+ efflux and K+ influx, while inducing expression of plasma membrane-type ATPase 7 (ZjAHA7) and high-affinity K+ transporter 2 (ZjHAK2) in roots. High K+/Na+ homeostasis was maintained throughout salt exposure. FA content was elevated in AM leaves as well as roots, especially for palmitic acid, oleic acid, trans oleic acid, and linoleic acid, and similar effects were also observed in AM poplar (Populus. alba × Populus. glandulosa cv. 84K) and Medicago truncatula, indicating AM symbiosis elevating FA levels could be a conserved physiological effect. Gene co-expression network analyses uncovered a core gene set including 267 genes in roots associated with AM symbiosis and conserved transcriptional responses, for example, FA metabolism, phytohormone signal transduction, SNARE interaction in vesicular transport, and biotin metabolism. In contrast to widely up-regulated genes related to FA metabolism in AM roots, limited genes were affected in leaves. We propose a model of AM symbiosis-linked reprogramming of FA metabolism and provide a comprehensive insight into AM symbiosis with a woody species adaptation to salt stress.

Bioactive Indole Alkaloid from Aspergillus amoenus TJ507 That Ameliorates Hepatic Ischemia/Reperfusion Injury.

Hepatic ischemia/reperfusion injury (IRI) is a major factor contributing to the failure of hepatic resection and liver transplantation. As part of our ongoing investigation into bioactive compounds derived from fungi, we isolated eight indole alkaloids (1-8) from the endophytic fungus Aspergillus amoenus TJ507. Among these alkaloids, one previously undescribed compound, amoenamide D (1), was identified. The planar structure of 1 was elucidated by extensive spectroscopic analysis, including HRESIMS and NMR spectra. The absolute configuration of 1 was elucidated by using electronic circular dichroism calculations. Notably, in the CoCl2-induced hepatocyte damage model, notoamide Q (3) exhibited significant anti-hypoxia injury activity. Furthermore, in a murine hepatic ischemia/reperfusion injury model, treatment with 3 prevents IRI-induced liver damage and hepatocellular apoptosis. Consequently, 3 might serve as a potential lead compound to prevent hepatic ischemia/reperfusion injury.

Tuft Cells Inhibit Pancreatic Tumorigenesis in Mice by Producing Prostaglandin D2.

BACKGROUND & AIMS: Development of pancreatic ductal adenocarcinoma (PDA) involves acinar to ductal metaplasia and genesis of tuft cells. It has been a challenge to study these rare cells because of the lack of animal models. We investigated the role of tuft cells in pancreatic tumorigenesis. METHODS: We performed studies with LSL-KrasG12D/+;Ptf1aCre/+ mice (KC; develop pancreatic tumors), KC mice crossed with mice with pancreatic disruption of Pou2f3 (KPouC mice; do not develop tuft cells), or mice with pancreatic disruption of the hematopoietic prostaglandin D synthase gene (Hpgds, KHC mice) and wild-type mice. Mice were allowed to age or were given caerulein to induce pancreatitis; pancreata were collected and analyzed by histology, immunohistochemistry, RNA sequencing, ultrastructural microscopy, and metabolic profiling. We performed laser-capture dissection and RNA-sequencing analysis of pancreatic tissues from 26 patients with pancreatic intraepithelial neoplasia (PanIN), 19 patients with intraductal papillary mucinous neoplasms (IPMNs), and 197 patients with PDA. RESULTS: Pancreata from KC mice had increased formation of tuft cells and higher levels of prostaglandin D2 than wild-type mice. Pancreas-specific deletion of POU2F3 in KC mice (KPouC mice) resulted in a loss of tuft cells and accelerated tumorigenesis. KPouC mice had increased fibrosis and activation of immune cells after administration of caerulein. Pancreata from KPouC and KHC mice had significantly lower levels of prostaglandin D2, compared with KC mice, and significantly increased numbers of PanINs and PDAs. KPouC and KHC mice had increased pancreatic injury after administration of caerulein, significantly less normal tissue, more extracellular matrix deposition, and higher PanIN grade than KC mice. Human PanIN and intraductal papillary mucinous neoplasm had gene expression signatures associated with tuft cells and increased expression of Hpgds messenger RNA compared with PDA. CONCLUSIONS: In mice with KRAS-induced pancreatic tumorigenesis, loss of tuft cells accelerates tumorigenesis and increases the severity of caerulein-induced pancreatic injury, via decreased production of prostaglandin D2. These data are consistent with the hypothesis that tuft cells are a metaplasia-induced tumor attenuating cell type.

Single Molecule Photocatalysis on TiO2 Surfaces.

Heterogeneous photocatalysis has been widely applied in various fields, such as photovoltaic cell, solar water splitting, photocatalytic pollutant degradation, and so on. Therefore, the reaction mechanisms involved in these important photocatalytic processes, especially in TiO2 photocatalysis, have been extensively investigated by various surface science techniques in the past decade. In this review, we highlight the recent progress that provides fundamental insights into TiO2 photocatalysis through direct tracking the evolution of single molecule photochemistry on TiO2 single crystal surfaces using a combination of scanning tunneling microscopy (STM) and other surface science techniques. Insight into the structures of various TiO2 surfaces is discussed first, which provides a basic concept on TiO2. Afterward, the details of the single molecule photocatalysis of several important molecules (water, alcohols, and aldehydes) on the model TiO2 surfaces are presented, which are trying to probe bond cleavages and the roles of adsorption sties and adsorption states in TiO2 photocatalysis step-by-step. Last, challenges and opportunities in single molecule photocatalysis on TiO2 are discussed briefly.

Organometallic polymers synthesized from prochiral molecules by a surface-assisted synthesis on Ag(111).

Organometallic polymers can be successfully synthesized on a Ag(111) surface via a surface-assisted synthesis by choosing prochiral 4,4'-dibromo-2,2'-bis(2-phenylethynyl)-1,1'-biphenyl (DBPB) molecules as the designed precursor. High-resolution scanning tunneling microscopy investigation reveals that prochiral molecules show chirality on a surface and can evolve into organometallic chains on the Ag(111) surface based on Ullmann coupling. Due to the special structural features of DBPB molecules, chiral selectivity will be lost in the organometallic polymers. This result may provide an important basis for selecting suitable precursors to fabricate chiral covalent nanostructures on a surface.

Quantitative insights into non-uniform plasmonic hotspots due to symmetry breaking induced by oblique incidence.

Localized surface plasmon resonance draws great attentions mainly due to its enhanced near electric field, i.e., plasmonic hotspots. The symmetry breaking via oblique incidence of light is predicted to influence the intensity of plasmonic hotspots. However, relevant experimental investigation in quantitative comparison with theory is still lacking. Here, we visualize the polarization-dependent plasmonic hotspots of a triangular Ag nanoplate through oblique-incidence photoemission electron microscopy (PEEM), revealing a non-uniform near-field enhancement. Under oblique incidence, two bright spots and one dark spot were identified in the polarization-averaged PEEM image, different from that for normal illumination where bright spots with equal intensity are anticipated. In polarization-dependent PEEM images, plasmonic hotspots appeared at specific corners of a triangular Ag nanoplate, and rotated in a manner consistent with the rotation of polarization angle. The experimental intensity maps of the photoelectron were well reproduced by simulation on a quantitative level. This work provides a quantitative understanding of how the orientation of incidence light relative to a plasmonic antenna influences the near-field enhancement.

Non-contact all-fiber optic laser Doppler accelerometer.

A non-contact all-fiber optic acceleration measurement system has been proposed in this work. Using a fiber delay line in the fiber-optic path, the difference between two Doppler shifted frequencies of a laser beam corresponding to two different velocities of a moving object with a fixed time delay was measured and used for acceleration extraction. By performing acceleration measurements for a piezoelectric ceramic oscillator driven by an open-loop piezo controller at different voltages, a measurement error of better than -3.766% and nonlinearity degree of 0.314% were achieved.

Fiber-optic, extrinsic Fabry-Perot interferometric dual-cavity sensor interrogated by a dual-segment, low-coherence Fizeau interferometer for simultaneous measurements of pressure and temperature.

A fiber-optic, extrinsic Fabry-Perot interferometric (EFPI), dual-cavity sensor made of sapphire was fabricated and interrogated by a dual-segment, low-coherence Fizeau interferometer to achieve simultaneous pressure and temperature measurements. The fiber-optic EFPI, dual-cavity sensor had an initial basal cavity length of 680 µm and an vacuum cavity length of 80 µm and was experimentally tested based on temperature and pressure measurements. It was demonstrated that simultaneous pressure and temperature measurement could be achieved in the respective pressure and temperature ranges of 0.1-3 MPa and 20-350 °C.

Elementary Chemical Reactions in Surface Photocatalysis.

Photocatalytic hydrogen evolution and organic degradation on oxide materials have been extensively investigated in the last two decades. Great efforts have been dedicated to the study of photocatalytic reaction mechanisms of a variety of molecules on TiO2 surfaces by using surface science methods under ultra-high vacuum (UHV) conditions, providing fundamental understanding of surface chemical reactions in photocatalysis. In this review, we summarize the recent progress in the study of photocatalysis of several important species (water, methanol, and aldehydes) on different TiO2 surfaces. The results of these studies have provided us deep insights into the elementary processes of surface photocatalysis and stimulated a new frontier of research in this area. Based on the results of these studies, a new dynamics-based photocatalysis model is also discussed.

Extrinsic Fabry-Perot interferometric cavity-based fiber-optic spectrum equalization filter for the Gaussian spectrum of superluminescent diodes.

To flatten the Gaussian spectrum of superluminescent diodes (SLDs), a fiber-optic spectrum equalization filter based on an extrinsic Fabry-Perot interferometric (EFPI) cavity is proposed. By the proper usage of a low-finesse EFPI cavity and the delicate design of a splitting and recombining fiber-optic path, the Gaussian spectrum of an SLD can be effectively flattened, which is verified by a numerical simulation and an experiment. An SLD with a center wavelength of 1568 nm and a 3-dB spectral width of 98 nm is spectrum-equalized to obtain a spectrum flatness of 0.27 dB in the wavelength range 1544.8-1605.6 nm. When the SLD is with a max power of 3.38 mW, the output power after the fiber-optic spectrum equalization filter can reach 178.06 µW.

Sensitivity-Enhanced Extrinsic Fabry-Perot Interferometric Fiber-Optic Microcavity Strain Sensor.

This study presents an extrinsic Fabry-Perot interferometric (EFPI) fiber-optic strain sensor with a very short cavity. The sensor consists of two vertically cut standard single-mode fibers (SMFs) and a glass capillary with a length of several centimeters. The two SMFs penetrate into the glass capillary and are fixed at its two ends with the use of ultraviolet (UV) curable adhesives. Based on the use of the lengthy glass capillary sensitive element, the strain sensitivity can be greatly enhanced. Experiments showed that the microcavity EPFI strain sensor with initial cavity lengths of 20 µm, 30 µm, and 40 µm, and a capillary length of 40 mm, can yield respective cavity length-strain sensitivities of 15.928 nm/µÎµ, 25.281 nm/µÎµ, and 40.178 nm/µÎµ, while its linearity was very close to unity for strain measurements spanning a range in excess of 3500 µÎµ. Furthermore, the strain-temperature cross-sensitivity was extremely low.

Absolute Single Cavity Length Interrogation of Fiber-Optic Compound Fabry⁻Perot Pressure Sensors Through a White Light Non-Scanning Correlation Method.

A white light non-scanning correlation interrogation system was proposed and built to interrogate absolute length of the air cavity of fiber-optic compound Fabry⁻Perot pressure sensors for the extraction of pressure value. By carefully choosing thickness range and tilt angle of the optical wedge used for cavity length matching, correlation interferometric signal of the basal cavity can be naturally filtered out. Based on peak positioning by Fourier transform, bandpass filtering in frequency domain, inverse Fourier transform back to time domain, envelope fitting and zero fringe finding through a gravity center method, cavity length can be determined with an accuracy of 0.04%. The system was used for the interrogation of a fiber-optic compound Fabry⁻Perot pressure sensor under different pressures. For a pressure range of 0.1~2.9 Mpa, the linear relationship between the air cavity length and the gas pressure imposed was successfully extracted.

A Zero-Cross Detection Algorithm for Cavity-Length Interrogation of Fiber-Optic Fabry-Perot Sensors.

A zero-cross detection algorithm was proposed for the cavity-length interrogation of fiber-optic Fabry-Perot (FP) sensors. The method can avoid the inaccuracy of peak determination in the conventional peak-to-peak method for the cavity-length interrogation of fiber-optic FP sensors caused by the slow variation of the spectral power density in peak neighboring regions. Both simulations and experiments were carried out to investigate the feasibility and performance of the zero-cross detection algorithm. Fiber-optic FP sensors with cavity lengths in the range of 150-1000 µm were successfully interrogated with a maximum error of 0.083 µm.

Key Processes of Silicon-On-Glass MEMS Fabrication Technology for Gyroscope Application.

MEMS fabrication that is based on the silicon-on-glass (SOG) process requires many steps, including patterning, anodic bonding, deep reactive ion etching (DRIE), and chemical mechanical polishing (CMP). The effects of the process parameters of CMP and DRIE are investigated in this study. The process parameters of CMP, such as abrasive size, load pressure, and pH value of SF1 solution are examined to optimize the total thickness variation in the structure and the surface quality. The ratio of etching and passivation cycle time and the process pressure are also adjusted to achieve satisfactory performance during DRIE. The process is optimized to avoid neither the notching nor lag effects on the fabricated silicon structures. For demonstrating the capability of the modified CMP and DRIE processes, a z-axis micro gyroscope is fabricated that is based on the SOG process. Initial test results show that the average surface roughness of silicon is below 1.13 nm and the thickness of the silicon is measured to be 50 µm. All of the structures are well defined without the footing effect by the use of the modified DRIE process. The initial performance test results of the resonant frequency for the drive and sense modes are 4.048 and 4.076 kHz, respectively. The demands for this kind of SOG MEMS device can be fulfilled using the optimized process.

Two-Parameter Elliptical Fitting Method for Short-Cavity Fiber Fabry⁻Perot Sensor Interrogation.

To solve the cavity interrogation problem of short cavity fiber Fabry⁻Perot sensors in white light spectral interrogation with amplified spontaneous emissions (ASEs) as the white light sources, a data processing method, using an improved elliptical fitting equation with only two undetermined coefficients, is proposed. Based on the method, the cavity length of a fiber Fabry⁻Perot sensor without a complete reflection spectrum period in the frequency domain can be interrogated with relatively high resolution. Extrinsic fiber Fabry⁻Perot air-gap sensors with cavity lengths less than 30 µm are used to experimentally verify the method, and are successfully interrogated with an accuracy better than 0.55%.

Elementary photocatalytic chemistry on TiO2 surfaces.

Photocatalytic hydrogen production and pollutant degradation provided both great opportunities and challenges in the field of sustainable energy and environmental science. Over the past few decades, we have witnessed fast growing interest and efforts in developing new photocatalysts, improving catalytic efficiency and exploring the reaction mechanism at the atomic and molecular levels. Owing to its relatively high efficiency, nontoxicity, low cost and high stability, TiO2 becomes one of the most extensively investigated metal oxides in semiconductor photocatalysis. Fundamental studies on well characterized single crystals using ultrahigh vacuum based surface science techniques could provide key microscopic insight into the underlying mechanism of photocatalysis. In this review, we have summarized recent progress in the photocatalytic chemistry of hydrogen, water, oxygen, carbon monoxide, alcohols, aldehydes, ketones and carboxylic acids on TiO2 surfaces. We focused this review mainly on the rutile TiO2(110) surface, but some results on the rutile TiO2(011), anatase TiO2(101) and (001) surfaces are also discussed. These studies provided fundamental insights into surface photocatalysis as well as stimulated new investigations in this exciting field. At the end of this review, we have discussed how these studies can help us to develop new photocatalysis models.

MicroRNA-146a feedback suppresses T cell immune function by targeting Stat1 in patients with chronic hepatitis B.

More than 350 million people are chronically infected with hepatitis B virus, and dysfunctional T cell responses contribute to persistent viral infection and immunopathogenesis in chronic hepatitis B (CHB). However, the underlying mechanisms of T cell hyporesponsiveness remain largely undefined. Given the important role of microRNA-146a (miR-146a) in diverse aspects of lymphocyte function, we investigated the potential role and mechanism of miR-146a in regulating T cell immune responses in CHB. We found that miR-146a expression in T cells is significantly upregulated in CHB compared with healthy controls, and miR-146a levels were correlated with serum alanine aminotransaminase levels. Both inflammatory cytokines and viral factors led to miR-146a upregulation in T cells. Stat1 was identified as a miR-146a target that is involved in antiviral cytokine production and the cytotoxicity of CD4(+) and CD8(+) T cells. In vitro blockage of miR-146a in T cells in CHB greatly enhanced virus-specific T cell activity. Therefore, our work demonstrates that miR-146a upregulation in CHB causes impaired T cell function, which may contribute to immune defects and immunopathogenesis during chronic viral infection.