Graphene-integrated mesh electronics with converged multifunctionality for tracking multimodal excitation-contraction dynamics in cardiac microtissues.

Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.

Evaluation of the effects of three different processing methods of aconite on rat metabolites based on high-coverage pseudotargeted metabolomics.

Aconite is the processed product of the seed root of Aconitum carmichaelii Debx. Aconite is a commonly used traditional Chinese medicine, which is generally used after processing. Black aconite, light aconite, and salted aconite are three different processed aconite products. They have the effects of restoring yang and saving energy enemy, dispersing cold, and relieving pain. However, clinical aconite poisoning cases have frequently been reported. In our study, we investigated the effects of three different processed aconite products on the changes of metabolites in vivo. A total of 42 rats were randomly divided into seven groups with six rats in each group. After three consecutive days of intragastric administration of 2.7 g/kg of the aconite-processed product, rat serums were obtained. The rat metabolites were detected using liquid chromatography-tandem mass spectrometry. The altered metabolites related to aconite-processed products were discovered by statistical analysis using metaboanalyst software. Our study is the first time to comprehensively evaluate the effects of three different processed aconite products on rat metabolites based on pseudotargeted metabolomics.

TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments.

T cell responses are inhibited by acidic environments. T cell receptor (TCR)-induced protein phosphorylation is negatively regulated by dephosphorylation and/or ubiquitination, but the mechanisms underlying sensitivity to acidic environments are not fully understood. Here, we found that TCR stimulation induced a molecular complex of Cbl-b, an E3-ubiquitin ligase, with STS1, a pH-sensitive unconventional phosphatase. The induced interaction depended upon a proline motif in Cbl-b interacting with the STS1 SH3 domain. STS1 dephosphorylated Cbl-b interacting phosphoproteins. The deficiency of STS1 or Cbl-b diminished the sensitivity of T cell responses to the inhibitory effects of acid in an autocrine or paracrine manner in vitro or in vivo. Moreover, the deficiency of STS1 or Cbl-b promoted T cell proliferative and differentiation activities in vivo and inhibited tumor growth, prolonged survival, and improved T cell fitness in tumor models. Thus, a TCR-induced STS1-Cbl-b complex senses intra- or extra-cellular acidity and regulates T cell responses, presenting a potential therapeutic target for improving anti-tumor immunity.

Revealing Variable Dependences in Hexagonal Boron Nitride Synthesis via Machine Learning.

Wafer-scale monolayer two-dimensional (2D) materials have been realized by epitaxial chemical vapor deposition (CVD) in recent years. To scale up the synthesis of 2D materials, a systematic analysis of how the growth dynamics depend on the growth parameters is essential to unravel its mechanisms. However, the studies of CVD-grown 2D materials mostly adopted the control variate method and considered each parameter as an independent variable, which is not comprehensive for 2D materials growth optimization. Herein, we synthesized a representative 2D material, monolayer hexagonal boron nitride (hBN), on single-crystalline Cu (111) by epitaxial chemical vapor deposition and varied the growth parameters to regulate the hBN domain sizes. Furthermore, we explored the correlation between two growth parameters and provided the growth windows for large flake sizes by the Gaussian process. This new analysis approach based on machine learning provides a more comprehensive understanding of the growth mechanism for 2D materials.

Low-thermal-budget synthesis of monolayer molybdenum disulfide for silicon back-end-of-line integration on a 200 mm platform.

Two-dimensional (2D) materials are promising candidates for future electronics due to their excellent electrical and photonic properties. Although promising results on the wafer-scale synthesis (≤150 mm diameter) of monolayer molybdenum disulfide (MoS2) have already been reported, the high-quality synthesis of 2D materials on wafers of 200 mm or larger, which are typically used in commercial silicon foundries, remains difficult. The back-end-of-line (BEOL) integration of directly grown 2D materials on silicon complementary metal-oxide-semiconductor (CMOS) circuits is also unavailable due to the high thermal budget required, which far exceeds the limits of silicon BEOL integration (<400 °C). This high temperature forces the use of challenging transfer processes, which tend to introduce defects and contamination to both the 2D materials and the BEOL circuits. Here we report a low-thermal-budget synthesis method (growth temperature < 300 °C, growth time ≤ 60 min) for monolayer MoS2 films, which enables the 2D material to be synthesized at a temperature below the precursor decomposition temperature and grown directly on silicon CMOS circuits without requiring any transfer process. We designed a metal-organic chemical vapour deposition reactor to separate the low-temperature growth region from the high-temperature chalcogenide-precursor-decomposition region. We obtain monolayer MoS2 with electrical uniformity on 200 mm wafers, as well as a high material quality with an electron mobility of ~35.9 cm2 V-1 s-1. Finally, we demonstrate a silicon-CMOS-compatible BEOL fabrication process flow for MoS2 transistors; the performance of these silicon devices shows negligible degradation (current variation < 0.5%, threshold voltage shift < 20 mV). We believe that this is an important step towards monolithic 3D integration for future electronics.

Correction: Highly reusable nanoporous silver sheet for sensitive SERS detection of pesticides.

Correction for 'Highly reusable nanoporous silver sheet for sensitive SERS detection of pesticides' by Huanyu Chi et al., Analyst, 2020, 145, 5158-5165, https://doi.org/10.1039/D0AN00999G.

Characterizing warm atmospheric boundary layer over land by combining Raman and Doppler lidar measurements.

PBL plays a critical role in the atmosphere by transferring heat, moisture, and momentum. The warm PBL has a distinct diurnal cycle including daytime convective mixing layer (ML) and nighttime residual layer developments. Thus, for PBL characterization and process study, simultaneous determinations of PBL height (PBLH) and ML height (MLH) are necessary. Here, new approaches are developed to provide reliable PBLH and MLH to characterize warm PBL evolution. The approaches use Raman lidar (RL) water vapor mixing ratio (WVMR) and Doppler lidar (DL) vertical velocity measurements at the Southern Great Plains (SGP) atmospheric observatory, which was established by the Atmospheric Radiation Measurement (ARM) user facility. Compared with widely used lidar aerosol measurements for PBLH, WVMR is a better trace for PBL vertical mixing. For PBLH, the approach classifies PBL water vapor structures into a few general patterns, then uses a slope method and dynamic threshold method to determine PBLH. For MLH, wavelet analysis is used to re-construct 2-D variance from DL vertical wind velocity measurements according to the turbulence eddy size to minimize the impacts of gravity wave and eddy size on variance calculations; then, a dynamic threshold method is used to determine MLH. Remotely-sensed PBLHs and MLHs are compared with radiosonde measurements based on the Richardson number method. Good agreements between them confirm that the proposed new algorithms are reliable for PBLH and MLH characterization. The algorithms are applied to warm seasons' RL and ML measurements at the SGP site for five years to study warm season PBL structure and processes. The weekly composited diurnal evolutions of PBLHs and MLHs in warm climate were provided to illustrate diurnal and seasonal PBL evolutions. This reliable PBLH and MLH dataset will be valuable for PBL process study, model evolution, and PBL parameterization improvement.

Cbl-b deficiency prevents functional but not phenotypic T cell anergy.

T cell anergy is an important peripheral tolerance mechanism. We studied how T cell anergy is established using an anergy model in which the Zap70 hypermorphic mutant W131A is coexpressed with the OTII TCR transgene (W131AOTII). Anergy was established in the periphery, not in the thymus. Contrary to enriched tolerance gene signatures and impaired TCR signaling in mature peripheral CD4 T cells, CD4SP thymocytes exhibited normal TCR signaling in W131AOTII mice. Importantly, the maintenance of T cell anergy in W131AOTII mice required antigen presentation via MHC-II. We investigated the functional importance of the inhibitory receptor PD-1 and the E3 ubiquitin ligases Cbl-b and Grail in this model. Deletion of each did not affect expression of phenotypic markers of anergic T cells or T reg numbers. However, deletion of Cbl-b, but not Grail or PD-1, in W131AOTII mice restored T cell responsiveness and signaling. Thus, Cbl-b plays an essential role in the establishment and/or maintenance of unresponsiveness in T cell anergy.

The "Two-Step" approach for classifying the severity of acute pancreatitis: A retrospective study.

BACKGROUND: The Revised Atlanta Classification (RAC) and Determinant-Based Classification (DBC) are currently two widely adopted systems for evaluating the severity of acute pancreatitis (AP). This study aimed to overcome the inaccuracies and limitations that existed in them. METHODS: We retrospectively analyzed 298 patients with AP. The "Two-Step" approach was divided into an early organ failure (OF) assessment: (I) none, (II) transient, (III) single persistent, and (IV) multiple persistent; and a later local complications assessment: (A) none, (B) sterile, and (C) infectious. Patients with AP who died before the second step were classified into category X. The "Two-Step" approach was then compared to the RAC and DBC. RESULTS: As the patients' grades increased (I to IV), organ support treatment rates, intensive care unit lengths of stay, and mortalities increased. Invasive intervention rates displayed increasing trends with local complications aggravated (A to C). Patients in category X were older and had higher Marshall scores with the highest grades of severity. CONCLUSIONS: By combining the early OF grades and the late local complications, the "Two-Step" approach represents an accurate classification system required for stratified studies of AP, and introduces the category X as the severest forms of AP.

Electrochemical Delamination of Ultralarge Few-Layer Black Phosphorus with a Hydrogen-Free Intercalation Mechanism.

Due to strong interlayer interaction and ease of oxidation issues of black phosphorus (BP), the domain size of artificial synthesized few-layer black phosphorus (FL-BP) crystals is often below 10 µm, which extremely limits its further applications in large-area thin-film devices and integrated circuits. Herein, a hydrogen-free electrochemical delamination strategy through weak Lewis acid intercalation enabled exfoliation is developed to produce ultralarge FL-BP single-crystalline domains with high quality. The interaction between the weak Lewis acid tetra-n-butylammonium acetate (CH3 COOTBA) and P atoms promotes the average domain size of FL-BP crystal up to 77.6 ± 15.0 µm and the largest domain size is found to be as large as 119 µm. The presence of H+ and H2 O is found to sharply decrease the size of as-exfoliated FL-BP flakes. The electronic transport measurements show that the delaminated FL-BP crystals exhibit a high hole mobility of 76 cm2 V-1 s-1 and an on/off ratio of 103 at 298 K. A broadband photoresponse from 532 to 1850 nm with ultrahigh responsivity is achieved. This work provides a scalable, simple, and low-cost approach for large-area BP films that meet industrial requirements for nanodevices applications.

Highly reusable nanoporous silver sheet for sensitive SERS detection of pesticides.

Surface-enhanced Raman spectroscopy (SERS) enables pesticide detection at the point-of-need, but its practical application is limited by expensive and disposable SERS substrates. Here, we report a reusable nanoporous silver (NPAg) sheet for the SERS detection of organochlorine pesticides, aiming to maximize the cost-efficiency of substrate regeneration. The NPAg sheet is prepared by a reduction-induced decomposition method without chemical induced random aggregations. This SERS substrate is sensitive to various analytes regardless of their affinity to a metal surface such as rhodamine B, dichlorodiphenyl-trichloroethane (DDT), and lindane due to its large surface area and the coral rock-like morphology. The SERS signal of lindane, a typical organochlorine pesticide, is identified and quantified with a minimum detectable concentration of 3 × 10-7 M (87 ppb), which is below the maximum residue limits in various foods set by the regulators across the world. More importantly, after a few minutes of ultrasonic cleaning in water, the NPAg sheet can be reused at least 20 times with a reproducible SERS activity. Furthermore, the NPAg sheet remains stable in terms of its sensitivity and reusability after several months of bare strorage. Therefore, the NPAg sheet as a SERS substrate holds great promise for mass production and convenient applications in low-cost pesticide analysis.

Modeling Dust in East Asia by CESM and Sources of Biases.

East Asian dust has a significant impact on regional and global climate. In this study, we evaluate the spatial distributions and temporal variations of dust extinction profiles and dust optical depth (DOD) over East Asia simulated from the Community Earth System Model (CESM) with satellite retrievals from Luo et al. (2015a, 2015b) (L15), Yu et al. (2015) (Y15), and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) level 3 (CAL-L3) products. Both L15 and Y15 are based on CALIPSO products but use different algorithms to separate dust from non-dust aerosols. We find high model biases of dust extinction in the upper troposphere over the Taklamakan Desert, Gobi Desert, and Tibetan Plateau, especially in the summer (June-July-August, JJA). CESM with dust emission scheme of Kok et al. (2014a, 2014b) has the best agreement with dust extinction profiles and DOD from L15 in the Taklamakan Desert and Tibetan Plateau. CESM with the default dust emission scheme of Zender et al. (2003a) underpredicts DOD in the Tibetan Plateau compared with observations from L15 due to the underestimation of local dust emission. Large uncertainties exist in observations from L15, Y15, and CAL-L3 and have significant impacts on the model evaluation of dust spatial distributions. We also assess dust surface concentrations and 10 m wind speed with meteorological records from weather stations in the Taklamakan and Gobi Deserts during dust events. CESM underestimates dust surface concentrations at most weather stations due to the inability of CESM to capture strong surface wind events.

Contrasting effects on deep convective clouds by different types of aerosols.

Convective clouds produce a significant proportion of the global precipitation and play an important role in the energy and water cycles. We quantify changes of the convective cloud ice mass-weighted altitude centroid (ZIWC) as a function of aerosol optical thickness (AOT). Analyses are conducted in smoke, dust and polluted continental aerosol environments over South America, Central Africa and Southeast Asia, using the latest measurements from the CloudSat and CALIPSO satellites. We find aerosols can inhibit or invigorate convection, depending on aerosol type and concentration. On average, smoke tends to suppress convection and results in lower ZIWC than clean clouds. Polluted continental aerosol tends to invigorate convection and promote higher ZIWC. The dust aerosol effects are regionally dependent and their signs differ from place to place. Moreover, we find that the aerosol inhibition or invigoration effects do not vary monotonically with AOT and the variations depend strongly on aerosol type. Our observational findings indicate that aerosol type is one of the key factors in determining the aerosol effects on convective clouds.

Tightening of tropical ascent and high clouds key to precipitation change in a warmer climate.

The change of global-mean precipitation under global warming and interannual variability is predominantly controlled by the change of atmospheric longwave radiative cooling. Here we show that tightening of the ascending branch of the Hadley Circulation coupled with a decrease in tropical high cloud fraction is key in modulating precipitation response to surface warming. The magnitude of high cloud shrinkage is a primary contributor to the intermodel spread in the changes of tropical-mean outgoing longwave radiation (OLR) and global-mean precipitation per unit surface warming (dP/dTs) for both interannual variability and global warming. Compared to observations, most Coupled Model Inter-comparison Project Phase 5 models underestimate the rates of interannual tropical-mean dOLR/dTs and global-mean dP/dTs, consistent with the muted tropical high cloud shrinkage. We find that the five models that agree with the observation-based interannual dP/dTs all predict dP/dTs under global warming higher than the ensemble mean dP/dTs from the ∼20 models analysed in this study.

Airborne compact rotational Raman lidar for temperature measurement.

We developed an airborne compact rotational Raman lidar (CRL) for use on the University of Wyoming King Air (UWKA) aircraft to obtain two-dimensional (2D) temperature disman tributions. It obtained fine-scale 2D temperature distributions within 3 km below the aircraft for the first time during the PECAN (Plains Elevated Convection At Night) campaign in 2015. The CRL provided nighttime temperature measurements with a random error of <0.5 K within 800 m below aircraft at 45 m vertical and 1000 m horizontal resolution. The temperatures obtained by the CRL and a radiosonde agreed. Along with water vapor and aerosol measurements, the CRL provides critical parameters on the state of the lower atmosphere for a wide range of atmospheric research.

Vertically resolved separation of dust and other aerosol types by a new lidar depolarization method.

This paper developed a new retrieval framework of external mixing of the dust and non-dust aerosol to predict the lidar ratio of the external mixing aerosols and to separate the contributions of non-spherical aerosols by using different depolarization ratios among dust, sea salt, smoke, and polluted aerosols. The detailed sensitivity tests and case study with the new method showed that reliable dust information could be retrieved even without prior information about the non-dust aerosol types. This new method is suitable for global dust retrievals with satellite observations, which is critical for better understanding global dust transportation and for model improvements.

CloudSat 2C-ICE product update with a new Ze parameterization in lidar-only region.

The CloudSat 2C-ICE data product is derived from a synergetic ice cloud retrieval algorithm that takes as input a combination of CloudSat radar reflectivity (Ze ) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation lidar attenuated backscatter profiles. The algorithm uses a variational method for retrieving profiles of visible extinction coefficient, ice water content, and ice particle effective radius in ice or mixed-phase clouds. Because of the nature of the measurements and to maintain consistency in the algorithm numerics, we choose to parameterize (with appropriately large specification of uncertainty) Ze and lidar attenuated backscatter in the regions of a cirrus layer where only the lidar provides data and where only the radar provides data, respectively. To improve the Ze parameterization in the lidar-only region, the relations among Ze , extinction, and temperature have been more thoroughly investigated using Atmospheric Radiation Measurement long-term millimeter cloud radar and Raman lidar measurements. This Ze parameterization provides a first-order estimation of Ze as a function extinction and temperature in the lidar-only regions of cirrus layers. The effects of this new parameterization have been evaluated for consistency using radiation closure methods where the radiative fluxes derived from retrieved cirrus profiles compare favorably with Clouds and the Earth's Radiant Energy System measurements. Results will be made publicly available for the entire CloudSat record (since 2006) in the most recent product release known as R05.

Compact airborne Raman lidar for profiling aerosol, water vapor and clouds.

A compact airborne Raman lidar system, which can perform water vapor and aerosol measurements both during nighttime and daytime is described. The system design, setup and the data processing methods are described in the paper. The Raman lidar was tested on University of Wyoming King Air research aircraft (UWKA) during the Wyoming King Air PBL Exploratory Experiment (KAPEE) in 2010. An observation showing clouds, aerosols and a dry line is presented to illustrate the lidar detection capabilities. Comparisons of the water vapor and aerosol measurements using the Raman lidar and other in situ airborne instruments show good agreement.

Early enteral nutrition with polymeric feeds was associated with chylous ascites in patients with severe acute pancreatitis.

OBJECTIVE: Chylous ascites (CA) may be involved in the pathological process of severe acute pancreatitis (SAP), but the underlying mechanisms remain unknown. This study investigated the incidence of CA in patients with SAP and its relationship with enteral nutrition (EN). METHODS: A retrospective review of 85 patients with SAP admitted to our hospital was performed. Patients starting EN within 72 hours after the onset of SAP were classified as the early EN (EEN) group, and others, as the later EN group. The incidences of CA and prognosis in the EEN and later EN groups were examined with nutrition preparation of polymeric formula or semielemental feed. RESULTS: Thirteen (15.29%) of 85 patients were identified with CA. A higher incidence of CA was observed in EEN patients who received polymeric formula (9 of 33, P < 0.05). All patients with CA were successfully treated with a modified medium-chain triglyceride diet. Consequently, there were no differences in intensive care unit stay and in mortality rates in patients with or without CA. CONCLUSIONS: There was a higher incidence of CA associated with early enteral feeding of polymeric formula in patients with SAP. Future studies are warranted to confirm our findings and evaluate better enteral feeding options to avoid CA.