bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin-associated lactic acidosis exacerbated by acute kidney injury in an overseas traveler
Authors: Hayashi Ayano , Ishimura Takuya , Sugimoto Hisashi , Suzuki Hiroyuki , Hamasaki Akihiro , Tsukamoto Tatsuo
Published: November 2021

We report the case of metformin-associated lactic acidosis (MALA) exacerbated by acute kidney injury (AKI) in a 65-year-old Asian American woman who was an overseas traveler. She had vomiting and diarrhea before arriving in Osaka, Japan, from the Philippines. She suffered from worsening respiratory distress, consciousness loss and anuria the day after coming to Japan. When she arrived at our emergency room via ambulance, she appeared to be in a state shock. Arterial blood gas analysis revealed severe lactic acidosis (pH 6.681, PO2 302 Torr under O2 supplementation, PCO2 15 Torr, HCO3−1.7 mmol/L, and lactate 17.00 mmol/L). She also had renal failure (BUN 108 mg/dL and serum creatinine 8.68 mg/dL) with hyperkalemia (6.1 mEq/L). We collected medical information from family members, and found her prescription medicines including metformin, diuretics and angiotensin-converting enzyme inhibitor (ACEI). We diagnosed her with MALA due to an unintended overdose of metformin resulting from acute kidney injury that can be induced by ACEI and diuretics in the volume-depleted condition. We immediately started hemodialysis therapy. Although she had a temporary cardiopulmonary arrest at the beginning of the treatment, her physical status was gradually improved and the severe acidemia resolved. On hospital day 4, she had urine and no longer needed hemodialysis therapy. On day 14, she was discharged and returned to the United States without noticeable sequelae. This is a case report of an overseas traveler who was successfully rescued through the collection of accurate medical information and understanding of the pathological condition.
Microstructure features and formation mechanism in a newly developed electroslag welding
Authors: Kakizaki Tomonori , Koga Shodai , Yamamoto Hajime , Mikami Yoshiki , Ito Kazuhiro , Yamazaki Kei , Sasakura Shuji , Watanabe Hirohisa
Published: November 2021

Electroslag welding (ESW) is known to show higher heat input than electrogas welding (EGW), resulting in poor low-temperature toughness. However, a newly developed ESW (dev. ESW) method using low-resistivity slag bath exhibited excellent low-temperature toughness as a result of lower effective heat input than conventional EGW, as demonstrated by the faster cooling rates measured in weld metals and estimated using finite element method analyses. This led to much shallower molten pool in the dev. ESW, resulting in much finer columnar grains and thinner centerline axial grains. High cooling speed in the dev. ESW method appeared to contribute to increased acicular ferrite proportion. The uniform microstructure with large acicular ferrite proportion and small number of inclusions in the weld metal permitted the dev. ESW weld metal to possess little variation in Charpy impact energy across the center of weld metal.
Heat transfer and film cooling measurements on aerodynamic geometries relevant for turbomachinery
Authors: Jagerhofer Patrick , Woisetschläger Jakob , Erlacher Gerhard , Göttlich Emil
Published: November 2021

A measurement technique for recording convective heat transfer coefficient and adiabatic film cooling effectiveness in demanding environments with highly curved surfaces and limited optical access, such as turbomachinery, is presented. Thermography and tailor-made flexible heating foils are used in conjunction with a novel multistep calibration and data reduction method. This method compensates for sensor drift, angle dependence of surface emissivity and window transmissivity, heat flux inhomogeneity, and conductive losses. The 2D infrared images are mapped onto the 3D curved surfaces and overlapped, creating surface maps of heat transfer coefficient and film cooling effectiveness covering areas significantly larger than the window size. The measurement technique’s capability is demonstrated in a sector-cascade test rig of a turbine center frame (TCF), an inherent component of modern two-spool turbofan engines. The horseshoe vortices were found to play a major role for the thermal integrity of turbine center frames, as they lead to a local increase in heat transfer, and at the same instance, to a reduction of film cooling effectiveness. It was also found that the horseshoe vortices lift off from the curved surface at 50% hub length, resulting in a pair of counter-rotating vortices. The measurement technique was validated by comparing the data against flat plate correlations and also by the linear relation between temperature difference and heat flux. This study is complemented with an extensive error and uncertainty analysis.

Article highlights

This paper presents an accurate measurement technique for heat transfer and film cooling

on 3D curved surfaces with limited optical access

using flexible tailor-made heating foils, infrared thermography and a high-fidelity multistep calibration process.

Graphical abstract
Dynamic generation of aqueous foams and fiber foams in a mixing tank
Authors: Prakash Baranivignesh , Kouko Jarmo , Luukkainen Veli-Matti , Jäsberg Ari , Koponen Antti I.
Published: November 2021

Mixing tanks are employed in paper and pulp industries to generate aqueous foams and fiber foams. The aim of the present study was to investigate the effect of impeller geometry on dynamic foam generation in a 60 L mixing tank. Three impeller geometries including two radial—Rushton turbine (RT), Bakker turbine (BT6), one axial high solidity pitched blade turbine (HSPBT), and four dual impeller combinations were investigated. Compressed air, water and sodium dodecyl sulphate were used as gas phase, liquid phase and surfactant, respectively, to generate aqueous foam. 1% mass consistency softwood fiber was used to generate fiber foam. The change in aqueous foam density for any given impeller was limited to ± 40 kg/m3 indicating foam density was dictated by impeller type rather than power input. Single impellers generated bubbly liquids whereas dual impellers generated low-density aqueous foams. Besides, stable foam was produced even at low power input compared to single impellers due to increase in impeller swept volume and blade contact area. Addition of fibers increased the foam density by ~ 100–150 kg/m3 and reduced the half-life time by almost threefold for all impellers due to lower air content and higher bubble size. Placement of high shear impeller (BT6) at bottom and down-pumping axial impeller (HSPBT) on top generated fine bubbles.
Golgi requires a new casting in the screenplay of mucopolysaccharidosis II cytopathology
Authors: Molnár Kinga , Kobolák Julianna , Dinnyés András
Published: November 2021

Lysosome (L), a hydrolytic compartment of the endo-lysosomal system (ELS), plays a central role in the metabolic regulation of eukaryotic cells. Furthermore, it has a central role in the cytopathology of several diseases, primarily in lysosomal storage diseases (LSDs). Mucopolysaccharidosis II (MPS II, Hunter disease) is a rare LSD caused by idunorate-2-sulphatase (IDS) enzyme deficiency. To provide a new platform for drug development and clarifying the background of the clinically observed cytopathology, we established a human in vitro model, which recapitulates all cellular hallmarks of the disease. Some of our results query the traditional concept by which the storage vacuoles originate from the endosomal system and suggest a new concept, in which endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and RAB2/LAMP positive Golgi (G) vesicles play an initiative role in the vesicle formation. In this hypothesis, Golgi is not only an indirectly affected organelle but enforced to be the main support of vacuole formation. The purposes of this minireview are to give a simple guide for understanding the main relationships in ELS, to present the storage vacuoles and their relation to ELS compartments, to recommend an alternative model for vacuole formation, and to place the Golgi in spotlight of MPS II cytopathology.
Street life and pedestrian activities in smart cities: opportunities and challenges for computational urban science
Authors: Fan Zhuangyuan , Loo Becky P.Y.
Published: November 2021

Ongoing efforts among cities to reinvigorate streets have encouraged innovations in using smart data to understand pedestrian activities. Empowered by advanced algorithms and computation power, data from smartphone applications, GPS devices, video cameras, and other forms of sensors can help better understand and promote street life and pedestrian activities. Through adopting a pedestrian-oriented and place-based approach, this paper reviews the major environmental components, pedestrian behavior, and sources of smart data in advancing this field of computational urban science. Responding to the identified research gap, a case study that hybridizes different smart data to understand pedestrian jaywalking as a reflection of urban spaces that need further improvement is presented. Finally, some major research challenges and directions are also highlighted.
STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery
Authors: Mathew Ginimol , Agha Riaz
Published: November 2021

ABSTRACT

Introduction:

Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines.

Methods:

A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise.

Results:

42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items.

Conclusion:

We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.

Highlights
Improving Predictions of Stream CO2 Concentrations and Fluxes Using a Stream Network Model: A Case Study in the East River Watershed, CO, USA
Authors: Saccardi Brian , Winnick Matthew
Published: November 2021

Inland waters are an important component of the global carbon budget. However, our ability to predict carbon fluxes from stream systems remains uncertain, as pCO2 varies within streams at scales of 1–100 m. This makes direct monitoring of large‐scale CO2 fluxes impractical. We incorporate CO2 input and output fluxes into a stream network advection‐reaction model, representing the first process‐based representation of stream CO2 dynamics at watershed scales. This model includes groundwater (GW) CO2 inputs, water column (WC), benthic hyporheic zone (BHZ) respiration, downstream advection, and atmospheric exchange. We evaluate this model against existing statistical methods including upscaling and multiple linear regressions through comparisons to high‐resolution stream pCO2 data collected across the East River Watershed in the Colorado Rocky Mountains (USA). The stream network model accurately captures GW, evasion, and respiration‐driven pCO2 variability and significantly outperforms multiple linear regressions for predicting pCO2. Further, the model provides estimates of CO2 contributions from internal versus external sources suggesting that streams transition from GW‐ to BHZ‐dominated sources between 3rd and 4th Strahler orders, with GW, BHZ, and WC accounting for 49.3%, 50.6%, and 0.1% of CO2 fluxes from the watershed, respectively. Lastly, stream network model atmospheric CO2 fluxes are 4‐12x times smaller than upscaling technique predictions, largely due to relationships between stream pCO2 and gas exchange velocities. Taken together, this stream network model improves our ability to predict stream CO2 dynamics and efflux. Furthermore, future applications to regional and global scales may result in a significant downward revision of global flux estimates.
Mechanisms for Late 20th and Early 21st Century Decadal AMOC Variability
Authors: Megann Alex , Blaker Adam , Josey Simon , New Adrian , Sinha Bablu
Published: November 2021

Recent studies using data from the OSNAP observational campaign and from numerical ocean models suggest that the Iceland Basin and the Irminger Sea may be more significant for formation of upper North Atlantic Deep Water than the Labrador Sea. Here, we present a set of hindcast integrations of a global 1/4° NEMO simulation from 1958 until nearly the present day, forced with three standard forcing data sets. We use the surface‐forced stream function, estimated from surface buoyancy fluxes, along with the overturning stream function, similarly defined in potential density space, to investigate the causal link between surface forcing and decadal variability in the strength of the Atlantic meridional overturning circulation (AMOC). We use the stream functions to demonstrate that watermasses in the simulations are transformed to higher densities as they propagate around the subpolar gyre from their formation locations in the north‐east Atlantic and the Irminger Sea, consistent with the picture emerging from observations. The surface heat loss from the Irminger Sea is confirmed to be the dominant mechanism for decadal AMOC variability, with the heat loss anomaly from the Labrador Sea having about half the magnitude. A scalar metric based on the surface‐forced stream function, accumulated in time, is found to be a good predictor of changes in the overturning strength. The AMOC variability is shown to be related to that of the North Atlantic Oscillation (NAO), primarily through the surface heat flux, itself dominated by the air‐sea temperature difference, but also with some local feedback from the SST to the surface fluxes.
Northeast China Cold Vortex Observed by FY‐3 MWTS‐2 and MetOp AMSU‐A
Authors: Niu Zeyi , Zou Xiaolei , Li Deqin
Published: November 2021

The northeast China cold vortex (NCCV) refers to a closed low‐pressure system over northeast China extending from China‐Siberia to the northwest Pacific coast region. It is cut off from the westerly jet belt in the middle and upper troposphere, has a cold core, lasts several days, and could bring heavy rain events in late spring and summer that are of great challenge to weather forecasters. This study investigates the possibility of observing temperature structures of NCCVs by two microwave temperature sounders, that is, the Microwave Temperature Sounder‐2 (MWTS‐2) and the Advanced Microwave Sounding Unit‐A (AMSU‐A) onboard the two polar‐orbiting operational environmental satellites (POES) Fenyun‐3 satellite FY‐3D and Meteorological Operational satellite MetOp‐B, respectively. The MWTS‐2 and AMSU‐A together provide 3D atmospheric temperatures in the middle and upper troposphere, as well as the lower stratosphere four times daily. Both limb‐corrected direct observations of brightness temperature and retrievals of atmospheric temperature within NCCVs are characterized by cold and warm cores below and above the tropopause, respectively, comparing favorably with the European Centre for Medium‐Range Weather Forecasts ERA5 reanalysis. Compared with the ERA5 reanalysis in June 2019, the MWTS‐2 retrieved atmospheric temperatures have no scan‐dependent biases, the biases are smaller than ±0.2K, and root‐mean‐square errors (RMSEs) are smaller than and 2.0K at all altitudes. This study suggests the possibility of using multiple POES microwave‐temperature‐sounding observations for near‐real‐time monitoring of NCCVs' 3D temperature structures.
Mesoscale Surface Wind‐SST Coupling in a High‐Resolution CESM Over the KE and ARC Regions
Authors: Tang Zhijia , Zhang Rong‐Hua , Wang Hongna , Zhang Shaoqing , Wang Hong
Published: November 2021

A strong positive correlation exists between mesoscale sea surface temperature (SST) and surface wind stress perturbations in the extratropical oceans, which is revealed by high‐resolution satellite but is difficult to be accurately simulated in low‐resolution coupled ocean‐atmosphere models. The extent to which the mesoscale coupling is captured in a high‐resolution Community Earth System Model (CESM‐HR) is assessed in this study, with a focus on two regions, the Kuroshio Extensions (KE) and Agulhas Return Current (ARC), respectively. Compared with satellite observations, it is found that the CESM‐HR can well depict the characteristics of the mesoscale air‐sea coupling, with its strength being comparable to that observed; but in the KE region, the simulated strength is only half of the observed during summer. Mechanisms for the atmospheric responses to mesoscale SST perturbations through the pressure adjustment (PA) and the downward momentum transport (DMT) are analyzed. The results highlight different mechanisms for controlling the atmospheric responses over the KE and ARC regions, which are regionally and seasonally dependent. In the ARC region, pronounced dipole patterns of sea surface pressure (SLP) and vertical velocity perturbation responses indicate that the DMT exerts a dominant effect in both winter and summer. In the KE region, monopole patterns show the main role played by the PA mechanism for the atmospheric adjustment in summer, while dipole patterns indicate the main role played by the DMT mechanism in winter. The weak coupling strength in summer over the KE is closely related to the inadequate parameterization of vertical heat mixing.
Deformation in SW Anatolia (Turkey) Documented by Anisotropy of Magnetic Susceptibility Data
Authors: Özkaptan Murat , Gülyüz Erhan , Uzel Bora , Langereis Cor G. , Özacar A. Arda , Kaymakcı Nuretdin
Published: November 2021

Convergence between the Eurasian and the African plates in the West Anatolian‐Aegean region results in a trench retreat due to slab roll‐back and tearing of the subducted African lithosphere. The upper plate response of this process gave way to back‐arc extension in the region. We have conducted a very detailed anisotropy of magnetic susceptibility (AMS) study on the Neogene rocks in SW Anatolia to unravel the style and magnitudes of deformation. For this purpose, from 83 sites in 11 structurally homogeneous domains, 1,680 paleomagnetic samples were analyzed. The results show that AMS fabrics are related to the tectonic deformation and that the magnetic lineation (maximum susceptibility axis, k1) is parallel to inferred maximum extension, while minimum susceptibility (k3) is typically normal to the bedding plane, corresponding to a preserved compaction associated with deposition fabric. The intermediate axis (k2) is parallel to a second extension direction and indicates that the region has been under the control of multi‐directional extension during the Neogene. Two main magnetic lineation directions are identified and represent Oligocene to middle Miocene E‐W, and late Miocene to Pliocene NW‐SE oriented extension. The magnetic lineation directions are dominantly parallel or perpendicular to the general strikes of the normal faults. The results show that the deformation in the region resembles two differentially stretched rubber sheets under the influence of SW oriented extension, exerted by the southward retreating Eastern Mediterranean subduction system.
Investigating Strike‐Slip Faulting Parallel to the Icelandic Plate Boundary Using Boundary Element Models
Authors: Pearson Anna E. R. , Loveless John P.
Published: November 2021

Most faults in Iceland strike roughly parallel to the divergent plate boundary, a part of the North American‐Eurasian plate boundary, which would be expected to lead to primarily normal faulting. However, several studies have observed a significant component of rift‐parallel strike‐slip faulting in Iceland. To investigate these fault kinematics, we use the boundary element method to model fault slip and crustal stress patterns of the Icelandic tectonic system, including a spherical hotspot and uniaxial stress that represents rifting. On a network of faults, we estimate the slip required to relieve traction imposed by hotspot inflation and remote rifting stress and compare the model results with observed slip kinematics, crustal seismicity, and geodetic data. We note a good fit between model‐predicted and observed deformation metrics, with both indicating significant components of normal and strike‐slip faulting and consistency between recent data and longer‐term records of geologic fault slip. Possible stress permutations between steeply plunging σ1 and σ2 axes are common in our models, suggesting that localized stress perturbations may impact strike‐slip faulting. Some increases in model complexity, including older hotspot configurations and allowing fault opening to simulate dike intrusion, show improvement to model fit in select regions. This work provides new insight into the physical mechanisms driving faulting styles within Iceland away from the current active plate boundary, implying that a significant portion of observed strike‐slip faulting is likely caused by the combined effects of tectonic rifting, hotspot impacts, and mechanical interactions across the fault network.
Psychological and biological resilience modulates the effects of stress on epigenetic aging
Authors: Harvanek Zachary M. , Fogelman Nia , Xu Ke , Sinha Rajita
Published: November 2021

Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-control moderated these relationships. Emotion regulation moderated the association between stress and aging (P = 8.82e−4) such that with worse emotion regulation, there was greater stress-related age acceleration, while stronger emotion regulation prevented any significant effect of stress on GrimAge. Self-control moderated the relationship between stress and insulin resistance (P = 0.00732), with high self-control blunting this relationship. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge Acceleration even while accounting for demographic, physiologic, and behavioral covariates. These results demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.
Initiation of hepatic stellate cell activation extends into chronic liver disease
Authors: De Smet Vincent , Eysackers Nathalie , Merens Vincent , Kazemzadeh Dastjerd Mina , Halder Georg , Verhulst Stefaan , Mannaerts Inge , van Grunsven Leo A.
Published: November 2021

Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.
MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance
Authors: Mehlich Dawid , Łomiak Michał , Sobiborowicz Aleksandra , Mazan Alicja , Dymerska Dagmara , Szewczyk Łukasz M. , Mehlich Anna , Borowiec Agnieszka , Prełowska Monika K. , Gorczyński Adam , Jabłoński Paweł , Iżycka-Świeszewska Ewa , Nowis Dominika , Marusiak Anna A.
Published: November 2021

Chemoresistance constitutes a major challenge in the treatment of triple-negative breast cancer (TNBC). Mixed-Lineage Kinase 4 (MLK4) is frequently amplified or overexpressed in TNBC where it facilitates the aggressive growth and migratory potential of breast cancer cells. However, the functional role of MLK4 in resistance to chemotherapy has not been investigated so far. Here, we demonstrate that MLK4 promotes TNBC chemoresistance by regulating the pro-survival response to DNA-damaging therapies. We observed that MLK4 knock-down or inhibition sensitized TNBC cell lines to chemotherapeutic agents in vitro. Similarly, MLK4-deficient cells displayed enhanced sensitivity towards doxorubicin treatment in vivo. MLK4 silencing induced persistent DNA damage accumulation and apoptosis in TNBC cells upon treatment with chemotherapeutics. Using phosphoproteomic profiling and reporter assays, we demonstrated that loss of MLK4 reduced phosphorylation of key DNA damage response factors, including ATM and CHK2, and compromised DNA repair via non-homologous end-joining pathway. Moreover, our mRNA-seq analysis revealed that MLK4 is required for DNA damage-induced expression of several NF-кB-associated cytokines, which facilitate TNBC cells survival. Lastly, we found that high MLK4 expression is associated with worse overall survival of TNBC patients receiving anthracycline-based neoadjuvant chemotherapy. Collectively, these results identify a novel function of MLK4 in the regulation of DNA damage response signaling and indicate that inhibition of this kinase could be an effective strategy to overcome TNBC chemoresistance.
ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY
Authors: Liu Danfei , Zhang Tongyue , Chen Xiaoping , Zhang Bixiang , Wang Yijun , Xie Meng , Ji Xiaoyu , Sun Mengyu , Huang Wenjie , Xia Limin
Published: November 2021

Metastasis is the predominant reason for high mortality of hepatocellular carcinoma (HCC) patients. It is critical to explore the molecular mechanism underlying HCC metastasis. Here, we reported that transcription factor One Cut homeobox 2 (ONECUT2) functioned as an oncogene to facilitate HCC metastasis. Elevated ONECUT2 expression was positively correlated with increased tumor number, tumor encapsulation loss, microvascular invasion, poor tumor differentiation, and advanced TNM stage. Mechanistically, ONECUT2 directly bound to the promoters of fibroblast growth factor 2 (FGF2) and ATP citrate lyase (ACLY) and transcriptionally upregulated their expression. Knockdown of FGF2 and ACLY inhibited ONECUT2-mediated HCC metastasis, whereas upregulation of FGF2 and ACLY rescued ONECUT2 knockdown-induced suppression of HCC metastasis. ONECUT2 expression was positively correlated with FGF2 and ACLY expression in human HCC tissues. HCC patients with positive coexpression of ONECUT2/FGF2 or ONECUT2/ACLY exhibited the worst prognosis. In addition, FGF2 upregulated ONECUT2 expression through the FGFR1/ERK/ELK1 pathway, which formed an FGF2-FGFR1-ONECUT2 positive feedback loop. Knockdown of ONECUT2 inhibited FGF2-induced HCC metastasis. Furthermore, the combination of FGFR1 inhibitor PD173074 with ACLY inhibitor ETC-1002 markedly suppressed ONECUT2-mediated HCC metastasis. In summary, ONECUT2 was a potential prognostic biomarker in HCC and targeting this oncogenic signaling pathway may provide an efficient therapeutic strategy against HCC metastasis.
The METTL3/MALAT1/PTBP1/USP8/TAK1 axis promotes pyroptosis and M1 polarization of macrophages and contributes to liver fibrosis
Authors: Shu Bo , Zhou Ying-Xia , Li Hao , Zhang Rui-Zhi , He Chao , Yang Xin
Published: November 2021

Pro-inflammatory M1 macrophages, via activating hepatic stellate cells, contribute to liver fibrosis. In this study, we examined the mechanism and the significance of a signaling axis, METTL3/MALAT1/PTBP1/USP8/TAK1, in regulating pyroptosis and M1 polarization of hepatic macrophages. Liver fibrosis model was established in vivo by CCl4 treatment; M1 polarization was induced in vitro by treating macrophages with lipopolysaccharide or interferon γ. Expressions of METTL3, MALAT1, PTBP1, USP8, and TAK1 were measured by RT-PCR and/or Western blot in Kupffer cells (KCs) isolated from in vivo model or in vitro activated macrophages. Macrophage phenotypes including inflammation (RT-qPCR analysis of a panel of proinflammatory cytokines and ELISA on productions of interleukin (IL)−1β and IL-18) and pyroptosis (Western blot of NLRP3, Caspase-1, and GSDMD) were investigated. The impact of METTL3 on m6A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays. Functional significance of individual component of METTL3/MALAT1/PTBP1/USP8/TAK1 axis was assessed by combining gain-of-function and loss-of-function approaches. In KCs isolated from in vivo liver fibrosis model or in vitro M1-polarized macrophages, METTL3 was up-regulated, and sequentially, it increased MALAT1 level via m6A methylation, which promoted USP8 mRNA degradation through the interaction with PTBP1. Reduced USP8 expression regulated the ubiquitination and protein stability of TAK1, which promoted pyroptosis and inflammation of macrophages. The signaling cascade METTL3/MALAT1/PTBP1/USP8/TAK1, by essentially stimulating pyroptosis and inflammation of macrophages, aggravates liver fibrosis. Therefore, targeting individual components of this axis may benefit the treatment of liver fibrosis.
Molecular recognition and photoprotection of riboflavin in water by a biomimetic host
Authors: Zhang Hong , Wang Li-Li , Pang Xin-Yu , Yang Liu-Pan , Jiang Wei
Published: November 2021

A water-soluble tetralactam macrocycle is synthesized and characterized. This macrocycle is able to strongly bind riboflavin (Ka >107 M−1) in water and provides strong photoprotection of riboflavin upon UV irradiation.
Sub-5 nm homeotropically aligned columnar structures of hybrids constructed by porphyrin and oligo(dimethylsiloxane)
Authors: Yang Weilu , Liu Dong , Luo Longfei , Li Peiyun , Liu Yun , Shen Zhihao , Lei Ting , Yang Huai , Fan Xing-He , Zhou Qi-Feng
Published: November 2021

Disc–coil hybrid liquid crystals containing porphyrin and oligo(dimethylsiloxane) can form lamellar and columnar phases that can also be transferred onto a silicone substrate with adjustable orientation.
Total syntheses of ericifolione and its analogues via a biomimetic inverse-electron-demand Diels–Alder reaction
Authors: Zhou Tingting , Zheng Anquan , Huo Luqiong , Li Changgeng , Tan Haibo , Wang Sasa , Chen Huiyu
Published: November 2021

A biomimetic tautomerization/intermolecular inverse-electron-demand hetero Diels–Alder reaction cascade to construct sterically hindered dihydropyran scaffolds was established and allowed the first total syntheses of ericifolione and analogues.
Against the NEER principle: the third type of photochromism for GFP chromophore derivatives
Authors: Liao Jun-Wei , Sung Robert , Sung Kuangsen
Published: November 2021

The third type of photochromism does not follow Z–E photoisomerization by τ-torsion, but undergoes light-driven φ-torsion, followed by ESIPT; it's against NEER principle since light-driven φ-torsion involves equilibration of excited-state rotamers.
Modified fullerenes as acceptors in bulk heterojunction organic solar cells – a theoretical study
Authors: Krishnan S. , Senthilkumar K.
Published: November 2021

In the present study, electronic structure calculations were used to provide strategies for designing poly(3-hexylthiophene) (P3HT)–fullerene-derivative-based donor–acceptor materials for use in high-efficiency bulk heterojunction organic solar cells (BHJ OSCs).
A CO2 utilization framework for liquid fuels and chemical production: techno-economic and environmental analysis
Authors: Do Thai Ngan , You Chanhee , Kim Jiyong
Published: November 2021

We analyzed the techno-economic and environmental performance of a wide-range of CO2-to-fuel pathways and the critical role of hydrogen in CO2 utilization framework.
Diosmetin alleviated cerebral ischemia/reperfusion injuryin vivoandin vitroby inhibiting oxidative stressviathe SIRT1/Nrf2 signaling pathway
Authors: Mei Zhigang , Du Lipeng , Liu Xiaolu , Chen Xiangyu , Tian Huan , Deng Yihui , Zhang Wenli
Published: November 2021

Diosmetin, a bioflavonoid that is abundant in dietary sources, could attenuate cerebral ischemia/reperfusion injury by inhibiting oxidative stressviathe SIRT1/Nrf2 signaling pathway bothin vivoandin vitro.
The differential modulatory effects ofEurotium cristatumon the gut microbiota of obese dogs and mice are associated with improvements in metabolic disturbances
Authors: Lu Xiaojie , Jing Yue , Li Yanyi , Zhang Naisheng , Zhang Wenlong , Cao Yongguo
Published: November 2021

Eurotium cristatum(E. cristatum) could reduce obesity in mice and dogs, and the antiobesity effect ofE. cristatumcan be attributed to gut microbiota. Our study implies thatE. cristatumhas potential as a probiotic to clinically treat obesity.
Non-volatile ternary memristors based on a polymer containing a carbazole donor with CuO NPs embedded
Authors: Dou Feng , Zhao Xiaofeng , Zhang Wanying , Zhang Yingna , Gao Meng , Chen Jiangshan , Wang Shuhong , Wang Cheng
Published: November 2021

A D–A-type polymer PCz–BMBI was synthesized and non-volatile ternary memory devices of ITO/PCz–BMBI:CuO/Al were fabricated with an ON2/ON1/OFF ratio of 105.3 : 102.3 : 1.
Wrinkle facilitated hydrogen evolution reaction of vacancy-defected transition metal dichalcogenide monolayers
Authors: Pu Mingjie , Guo Yufeng , Guo Wanlin
Published: November 2021

The combination of wrinkle engineering and defect engineering for the application of transition metal dichalcogenides (TMDs) in hydrogen production.
Redox deracemization of phosphonate-substituted dihydropyrimidines
Authors: Meng Fan-Jie , Shao Bing-Ru , Velopolcek Maria K. , Guo Xuan , Feng Guang-Shou , Shi Lei
Published: November 2021

An efficient one-pot redox deracemization of the phosphonic ester substituted 3,4-dihydropyrimidin-2-one (DHPM) derivatives is described, providing a series of optically active phosphonate substituted DHPMs with up to 96% ee.
Electrochemical regioselective C–H selenylation of 2H-indazole derivatives
Authors: Lin Shengsheng , Cheng Xiaomei , Hasimujiang Balati , Xu Zhongnan , Li Fengtan , Ruan Zhixiong
Published: November 2021

A metal- and oxidant-free, electrochemical strategy for the regioselective selenylation of 2H-indazole derivatives has been developed, with broad substrate scope and moderate to good yields, under mild and environment-friendly reaction conditions.
Polycyclic aromatic hydrocarbon-based organic semiconductors: ring-closing synthesis and optoelectronic properties
Authors: Li Qingbin , Zhang Yihan , Xie Ziyi , Zhen Yonggang , Hu Wenping , Dong Huanli
Published: November 2021

Polycyclic aromatic hydrocarbons (PAHs) as a typical class of organic semiconductors demonstrate unique optical, electrical, magnetic and other interesting properties due to their extended conjugation and diverse structures.
Intelligent task migration with deep Qlearning in multi‐access edge computing
Authors: Huang Sheng‐Zhi , Lin Kun‐Yu , Hu Chin‐Lin
Published: November 2021

Multi‐access edge computing provides computation and network resources in proximity to user applications in mobile environments. Deploying edge servers in network boundary can not only offload the heavy task loading on the cloud, but also alleviate resource‐limited capabilities of mobile devices. Rather than many stand‐alone edge servers, the concept of multi‐server edge computing is recently advocated to contend with the issues of system scalability and service quality against dynamic task workload. This study exploits collaborative computing resources and designs a task migration strategy for multiple edge servers in mobile networks. This study formulates a queueing optimization problem of minimizing the overall service time in a multi‐server system. An intelligent task migration scheme is then developed using the deep reinforcement learning and Q‐learning techniques. With a variety of numerical attributes derived from the queueing model, this intelligent scheme can arrange the task distribution among edge servers to enhance the task processing capability. Simulation‐based results show that the proposed task migration scheme can sustain service efficiency and resource utilization, which is promising as compared with conventional designs without collaborative intelligence in mobile environments.
Distributed deep reinforcement learning for integrated generation‐control and power‐dispatch of interconnected power grid with various renewable units
Authors: Li Jiawen , Yao Jianguo , Yu Tao , Zhang Xiaoshun
Published: November 2021

To mismatch various power disturbances of interconnected power grid, an integrated generation‐control and power‐dispatch (IGCPD) for performance‐based frequency regulation market is proposed. Unlike the conventional automatic generation control with an independent controller and a power distributor, IGCPD can significantly improve the dynamic control performance via combining these two parts into an integrated decision agent. The IGCPD eliminates the waste of frequency regulation resources and repeated regulation of the units caused by the mismatch of the controller and power distributor. In addition, by setting the reward function reasonably, IGCPD can save regulatable capacity of fast units for regulation in the next large‐scale disturbance. In order to enhance the decision ability, a swarm intelligence‐based deep deterministic policy gradient (SI‐DDPG) algorithm is proposed to acquire the control knowledge and implement a high‐quality decision for this agent. Moreover, the swarm intelligence‐based training sample can achieve a high learning robustness for SI‐DDPG which solve the problem of low robustness in conventional deep reinforcement learning. The proposed technique is verified on an England two‐area load frequency control model and the west China two‐area LFC model. IGCPD improves the area control error control performance and reduce the frequency regulation mileage payment of the interconnected power grid.
Large-scale magnetic field in the Monoceros OB 1 east molecular cloud
Authors: Alina D. , Montillaud J. , Hu Y. , Lazarian A. , Ristorcelli I. , Abdikamalov E. , Sagynbayeva S. , Juvela M. , Liu T. , Carrière J.-S.
Published: November 2021

Context. The role of large-scale magnetic fields in the evolution of star-forming regions remains elusive. Its investigation requires the observational characterization of well-constrained molecular clouds. The Monoceros OB 1 molecular cloud is a large complex containing several structures that have been shown to be engaged in an active interaction and to have a rich star formation history. However, the magnetic fields in this region have only been studied on small scales.

Aims. We study the large-scale magnetic field structure and its interplay with the gas dynamics in the Monoceros OB 1 east molecular cloud.

Methods. We combined observations of dust polarized emission from the Planck telescope and CO molecular line emission observations from the Taeduk Radio Astronomy Observatory 14-metre telescope. We calculated the strength of the plane-of-sky magnetic field using a modified Chandrasekhar-Fermi method and estimated the mass-over-flux ratios in different regions of the cloud. We used the comparison of the velocity and intensity gradients of the molecular line observations with the polarimetric observations to trace dynamically active regions.

Results. The molecular complex shows an ordered large-scale plane-of-sky magnetic field structure. In the northern part, it is mostly orientated along the filamentary structures, while the southern part shows at least two regions with distinct magnetic field orientations. Our analysis reveals a shock region in the northern part right between two filamentary clouds that, in previous studies, were suggested to be involved in a collision. The magnetic properties of the north-main and north-eastern filaments suggest that these filaments once formed a single one, and that the magnetic field evolved together with the material and did not undergo major changes during the evolution of the cloud. In the southern part, we find that either the magnetic field guides the accretion of interstellar matter towards the cloud or it is dragged by the matter falling towards the main cloud.

Conclusions. The large-scale magnetic field in the Monoceros OB 1 east molecular cloud is tightly connected to the global structure of the complex. In the northern part, it seems to serve a dynamically important role by possibly providing support against gravity in the direction perpendicular to the field and to the filament. In the southern part, it is probably the most influential factor governing the morphological structure by guiding possible gas inflow. A study of the whole Monoceros OB 1 molecular complex at large scales is necessary to form a global picture of the formation and evolution of the Monoceros OB 1 east cloud and the role of the magnetic field in this process.
ESASky SSOSS: Solar System Object Search Service and the case of Psyche
Authors: Racero E. , Giordano F. , Carry B. , Berthier J. , Müller T. , Mahlke M. , Valtchanov I. , Baines D. , Kruk S. , Merín B. , Besse S. , Küppers M. , Puga E. , González Núñez J. , Rodríguez P. , de la Calle I. , López-Marti B. , Norman H. , Wångblad M. , López-Caniego M. , Álvarez Crespo N.
Published: November 2021

Context. The store of data collected in public astronomical archives across the world is continuously expanding and, thus, providing a convenient interface for accessing this information is a major concern for ensuring a second life for the data. In this context, Solar System objects (SSOs) are often difficult or even impossible to query, owing to their ever-changing sky coordinates.

Aims. Our study is aimed at providing the scientific community with a search service for all potential detections of SSOs among the ESA astronomy archival imaging data, called the Solar System Object Search Service (SSOSS). We illustrate its functionalities using the case of asteroid (16) Psyche, for which no information in the far-IR (70–500 μm) has previously been reported, to derive its thermal properties in preparation for the upcoming NASA Psyche mission.

Methods. We performed a geometrical cross-match of the orbital path of each object, as seen by the satellite reference frame, with respect to the public high-level imaging footprints stored in the ESA archives. There are about 800 000 asteroids and 2000 comets included in the SSOSS, available through ESASky, providing both targeted and serendipitous observations. For this first release, three missions were chosen: XMM-Newton, the Hubble Space Telescope (HST), and Herschel.

Results. We present a catalog listing all potential detections of asteroids within estimated limiting magnitude or flux limit in Herschel, XMM-Newton, and HST archival imaging data, including 909 serendipitous detections in Herschel images, 985 in XMM-Newton Optical Monitor camera images, and over 32 000 potential serendipitous detections in HST images. We also present a case study: the analysis of the thermal properties of Psyche from four serendipitous Herschel detections, combined with previously published thermal IR measurements. We see strong evidence for an unusual drop in (hemispherical spectral) emissivity, from 0.9 at 100 μm down to about 0.6 at 350 μm, followed by a possible but not well-constrained increase towards 500 μm, comparable to what was found for Vesta. The combined thermal data set puts a strong constraint on Psyche’s thermal inertia (between 20 to 80 J m−2 s−1/2 K−1) and favors an intermediate to low level surface roughness (below 0.4 for the rms of surface slopes).

Conclusions. Using the example of Psyche, we show how the SSOSS provides fast access to observations of SSOs from the ESA astronomical archives, regardless of whether the particular object was the actual target. This greatly simplifies the task of searching, identifying and retrieving such data for scientific analysis.
KDIGO-Leitlinien 2021 zur Glomerulonephritis – Focus ANCA-assoziierte Vaskulitiden und antiglomeruläre Basalmembran-Nephritis
Authors: de Groot Kirsten , Haubitz Marion , Rupprecht Harald D. , Schönermarck Ulf
Published: November 2021

Was ist neu?

Klinische, serologische, histopathologische Diagnostik der ANCA-assoziierten Vaskulitis Zentraler Bestandteil der Diagnostik der AAV mit renaler Manifestation sind die Bestimmung von PR3- und MPO-ANCA sowie die Nierenbiopsie. Die Behandlung sollte in einem in AAV erfahrenen Zentrum erfolgen und rasch begonnen werden.

Remissionsinduktion Die Remissionsinduktion bei ANCA-assoziierter GN erfolgt mit Cyclophosphamid oder Rituximab in Kombination mit Kortikosteroiden. Die Leitlinie gibt Hilfestellung zur Therapieauswahl. Studienbasiert wird eine schnellere Steroidreduktion empfohlen.

Remissionserhaltung Zur Remissionserhaltung stehen Rituximab und Azathioprin zur Verfügung. Die Leitlinie gibt Hilfestellung zu Auswahl und Dauer der Therapie, die sich insbesondere nach dem Rezidivrisiko richtet.

Anti-GBM-Erkrankung Die Plasmapherese gehört zur Standardtherapie der Anti-GBM-Erkrankung, ist jedoch bei der ANCA-assoziierten GN einer Einzelfallentscheidung bei fulminantem Verlauf vorbehalten.

Transplantation Eine Nierentransplantation kann bei ANCA-assoziierter GN nach mindestens 6-monatiger Remission unabhängig vom ANCA-Status erfolgen, bei Patienten mit Anti-GBM-Erkrankung nur nach negativem Antikörpernachweis.