bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking the “Race” Out of Master Race: The Evolving Role of the Jew in White Supremacist Discourse
Authors: Rosenberg Emma
Published: January 2023

Across Europe and North America, political leaders and elites use ethnoreligious appeals based on white supremacist ideology with increasing success. Yet this rhetoric frequently includes positive references to Jews and Israel. What explains this pivot away from the historic reliance on the so-called “nefarious, menacing Jew”? Rather than interpret the transformation of the white supremacist Jewish trope as an ideological shift, this article demonstrates that the transformation reflects a mainstreaming of white supremacist discourse. More specifically, as white supremacist discourse increasingly finds a home in successful nativist political parties, framing Jews as a religion rather than a race sidesteps hurdles to attracting votes. Second, positive references to Israel rather than Jews demonstrates the evolution of an identitarian strand within white supremacy rather than a de-escalation of racist ideology. A comparison of the German AfD and the American Republican Party, two parties that increasingly employ white supremacist rhetoric alongside pro- Jewish rhetoric, illustrates the phenomenon. Within a larger political context, the de-racializing of Jews in white supremacist discourse reflects a shift in twenty-first century nativism from a preoccupation with race and nationality, to a focus on civilizational, cultural, and religious identities.
ZERO DENSITY THEOREMS FOR FAMILIES OF DIRICHLET L-FUNCTIONS
Authors: CORRIGAN CHANDLER C. , ZHAO LIANGYI
Published: January 2023

We prove some zero density theorems for certain families of Dirichlet L-functions. More specifically, the subjects of our interest are the collections of Dirichlet L-functions associated with characters to moduli from certain sparse sets and of certain fixed orders.
ON ARITHMETIC SUMS OF CONNECTED SETS IN
Authors: WU YU-FENG
Published: January 2023

We prove that for two connected sets
$E,F\subset \mathbb {R}^2$
with cardinalities greater than
$1$
, if one of E and F is compact and not a line segment, then the arithmetic sum
$E+F$
has nonempty interior. This improves a recent result of Banakh et al. [‘The continuity of additive and convex functions which are upper bounded on non-flat continua in
$\mathbb {R}^n$
’, Topol. Methods Nonlinear Anal.54(1)(2019), 247–256] in dimension two by relaxing their assumption that E and F are both compact.
Phylogenetic relationships and further unknown diversity of diplostomids (Diplostomida: Diplostomidae) parasitic in kingfishers
Authors: Achatz T.J. , Von Holten Z.S. , Kipp J.W. , Fecchio A. , LaFond L.R. , Greiman S.E. , Martens J.R. , Tkach V.V.
Published: January 2023

Kingfishers (Alcedinidae Rafinesque) are common inhabitants of wetlands and are known to be definitive hosts to a wide range of digeneans that parasitize fish as second intermediate hosts. Among these digeneans, members of the Diplostomidae Poirier, 1886 (diplostomids) are particularly common. Recent studies of diplostomids collected from kingfishers have revealed that they are probably more diverse than currently known. This particularly concerns the genera Crassiphiala Van Haitsma, 1925 and Uvulifer Yamaguti, 1934. In the present work, we studied seven diplostomid taxa from kingfishers in Brazil, the USA and the Philippines. Partial DNA sequences of the nuclear large ribosomal subunit (28S) and mitochondrial cytochrome c oxidase I (cox1) genes were obtained, and 28S sequences were used to study the phylogenetic interrelationships of these diplostomids. We provide the first DNA sequences from Uvulifer semicircumcisus Dubois et Rausch, 1950 and a member of Subuvulifer Dubois, 1952. Pseudocrassiphiala n. gen. is erected for a previously recognized species-level lineage of Crassiphiala and a new generic diagnosis of Crassiphiala is provided. Crassiphiala jeffreybelli n. sp., Crassiphiala wecksteini n. sp. and Pseudocrassiphiala tulipifera n. sp. are described, and a description of newly collected, high-quality specimens of Crassiphiala bulboglossa Van Haitsma, 1925 (the type-species of the genus) is provided.
Use of antimicrobials in the treatment of calf diarrhea: a systematic review
Authors: Bernal-Córdoba C. , Branco-Lopes R. , Latorre-Segura L. , de Barros-Abreu M. , Fausak E. D. , Silva-del-Río N.
Published: January 2023

The objective of this study was to conduct a systematic review of the scientific literature evaluating the efficacy and comparative efficacy of antimicrobials (AMs) for the treatment of diarrhea in calves. Eligible studies were non- and randomized controlled trials evaluating an AM intervention against a positive and negative control, with at least one of the following outcomes: fecal consistency score, fever, dehydration, appetite, attitude, weight gain, and mortality. Four electronic databases were searched. Titles and abstracts (three reviewers) and full texts (two reviewers) were screened. A total of 2899 studies were retrieved; 11 studies met the inclusion criteria. The risk of bias was assessed. Most studies had incomplete reporting of trial design and results. Eight studies compared AMs to a negative control (placebo or no treatment). Among eligible studies, the most common outcomes reported were diarrhea severity (n= 6) and mortality (n= 6). Eligible studies evaluated very different interventions and outcomes; thus, a meta-analysis was not performed. The risk of bias assessment revealed concerns with reporting of key trial features, including disease and outcome definitions. Insufficient evidence is available in the scientific literature to assess the efficacy of AMs in treating calf diarrhea.
Definition of low birth weight in domestic mammals: a scoping review
Authors: Mugnier Amélie , Chastant Sylvie , Lyazrhi Faouzi , Saegerman Claude , Grellet Aurélien
Published: January 2023

In people and animals, low birth weight (LBW) is recognized as highly predictive of health trajectory from the neonatal period to elderly ages. Regarding the neonatal period, although LBW is recognized as a major risk factor for neonatal mortality, there does not appear to be a clear definition of ‘when a birth weight should be considered low’ in all species. The aim of this work was to use the scientific literature available to map the various thresholds proposed to define LBW in domestic mammals. Using a standardized methodology, a scoping review was conducted through a literature search in three different bibliographic databases. After a two-step screening of 1729 abstracts and full-text publications by two independent reviewers, eleven studies met the inclusion criteria. Selected publications represented six mammalian species (rat, mouse, dog, pig, cow, and rabbit). Birth weight thresholds were identified through six different methods. In addition to the scarcity of scientific literature about the definition of LBW, this scoping review revealed the lack of standardization for the description, evaluation or the pertinence these definitions. Because the health consequences of LBW could be preventable, providing early identification of at-risk neonates, a consensus for the standardized definition of LBW is required.
New Investment Rulemaking in Asia: Between Regionalism and Domestication
Authors: Hsieh Pasha L.
Published: January 2023

The article analyses investment rulemaking in new Asian regionalism in the context of evolving national legislation and regional trade strategies. It argues that the Association of Southeast Asian Nations (ASEAN) and the Regional Comprehensive Economic Partnership (RCEP) represent Asia's pragmatic incrementalism in reforming the investment regime. The process reinforces the relationship between international economic law and domestic investment laws. In tandem with transforming international investment agreements, ASEAN expedited investment and services trade, and established the modern investor–state dispute settlement (ISDS) mechanism. The RCEP further buttresses the ASEAN centrality in regional frameworks by consolidating ASEAN Plus One agreements. Yet, the RCEP's omission of ISDS reflects a distinct approach that may confront challenges to state-to-state proceedings and treaty shopping under overlapping pacts. Finally, the research sheds light on Asian countries' recent investment agreements and domestic dispute settlement that complement the liberal international order. These developments provide valuable models for developing countries and contribute to the understanding of global investment reforms from an Asian perspective.
The Past, Present, and Future of Domestic Investment Laws and International Economic Law
Authors: Hepburn Jarrod
Published: January 2023

This article considers the past, present, and future of domestic investment laws. Its focus is on the ‘facilitative’ investment law, which aims to encourage foreign investment by granting substantive protections to foreign investors and consent to international arbitration over disputes with foreign investors. The article first contends that states had independent reasons to enact such facilitative investment laws alongside investment treaties, even though investment treaties perform very similar functions. Secondly, the article argues that investment laws can be characterized either as unilaterally assumed international obligations of states or simply as domestic laws of states, with differing consequences under each characterization. Thirdly, the article proposes four possible futures for facilitative investment laws: contamination, continuation, compromise, and contestation.
Spontaneous dissection of the superior mesenteric artery related to COVID-19
Authors: Kukulski Leszek , Scharf Gregor , Schierling Wilma , Pfister Karin , Linnemann Birgit
Published: January 2023

Summary: Background: Spontaneous peripheral dissections are rare, and in a substantial number of cases, the underlying aetiology remains unclear. Patients and methods: We report the case of a 63-year-old male patient with a recent asymptomatic SARS-CoV-2 infection who presented with sudden-onset intermittent abdominal pain. Imaging studies revealed a dissection of the superior mesenteric artery (SMA) and large-vessel vasculitis involving the SMA as well as the carotid, subclavian, axillary and femoropopliteal arteries. In the absence of other predisposing factors, we supposed an association with prior COVID-19 and performed a systematic review of the literature to search for similar cases with arterial dissection related to acute or recent SARS-CoV-2 infection. Results: We identified 25 cases, including ours: 13 males and 12 females, with a median age of 48 years. In 22/25 patients, arterial dissection occurred within 4 weeks after the diagnosis of COVID-19 and involved the cerebral (11/25; 44%), coronary (10/25; 40%), splanchnic (3/25; 12%) and renal (2/25; 8%) arteries. Conclusions: Although initially known for its respiratory manifestations, it has become evident that SARS-CoV-2 not only infects pneumocytes but also enters the vascular endothelium, leading to endothelial dysfunction and hypercoagulability and – as shown in our case – large-vessel vasculitis, which may predispose patients to intramural haemorrhage and arterial dissection.
Entwicklung und Überprüfung eines Fragebogens zur Erfassung studentischer Bedarfe an medienbezogenen Lehrkompetenzen im Lehramtsstudium
Authors: Henning-Kahmann Jan , Hellmann Katharina
Published: January 2023

Zusammenfassung. Um Schülerinnen und Schüler beim Erwerb erforderlicher Kompetenzen für den Umgang mit neuen, digitalen Technologien bzw. Medien adäquat zu unterstützen und diese lernförderlich im Unterricht einzusetzen, benötigen Lehrkräfte nicht nur eigene Medienkompetenzen, sondern insbesondere medienbezogene Lehrkompetenzen. Eine zielgruppen- und kompetenzorientierte Gestaltung hochschulischer Maßnahmen zur Förderung dieser Kompetenzen im Lehramtsstudium setzt jedoch die konkrete Identifizierung von Bedarfen aus studentischer Perspektive voraus. Bislang fehlt es an einem geeigneten Instrument, um die aus wahrgenommenen Kompetenzdefiziten hervorgehenden, individuellen Bedarfe umfassend und reliabel zu erfassen. Ausgehend von einem heuristischen Rahmenmodell medienbezogener Kernkompetenzen von Lehrkräften ( Forschungsgruppe Lehrerbildung Digitaler Campus Bayern [FLDCB], 2017 ) beschreibt der vorliegende Beitrag die Entwicklung und psychometrische Überprüfung eines Fragebogens zur Erfassung selbsteingeschätzter Bedarfe an medienbezogenen Lehrkompetenzen im Lehramtsstudium. Im Rahmen konfirmatorischer Faktorenanalysen wurde die Dimensionalität des Instruments mittels des „detection of misspecification“-Ansatzes ( Saris, Satorra & van der Veld, 2009 ) untersucht und dessen Reliabilität einer erweiterten Prüfung unterzogen. Basierend auf einer Vorstudie ( N = 254) wurden zunächst einige Items überarbeitet. Die Überprüfung des revidierten Instruments in der Hauptstudie ( N = 232) ergab ein fünffaktorielles Modell und zeigte, dass sich die individuellen Bedarfe bezüglich medienbezogener Lehrkompetenzen mit Hilfe der entsprechenden Dimensionen (Planung, Entwicklung, Realisierung, Evaluation, Sharing) differenzieren lassen. Zudem konnte durch ein Bifaktor-(S-1)-Modell gezeigt werden, dass ein übergeordneter Generalfaktor nicht ausreichend zur Varianzaufklärung beiträgt und statt eines Gesamttestwerts die einzelnen, reliablen Subskalenwerte verwendet werden sollten. Erste Hinweise auf konvergente Validität sprechen zudem für eine valide Interpretierbarkeit der Testwerte. Trotz weiteren Forschungsbedarfs bietet das vorgestellte Instrument eine Möglichkeit, selbsteingeschätzte Bedarfe an medienbezogenen Lehrkompetenzen im Lehramtsstudium reliabel und ökonomisch zu erfassen, wodurch sich verschiedenste Anwendungsszenarien im Hochschul- und Forschungskontext eröffnen.
Misclassification of Self-Directed Violence
Authors: Teismann Tobias , Eimen Jannik Julian , Cwik Jan Christopher
Published: January 2023

Abstract: Background: Classification of acts of self-directed violence has been shown to be inadequate in past research. Furthermore, level of expertise have been shown to be unrelated to classification correctness. Aim: The aim of the present study was to investigate whether participants provided with a definition are more reliable in their judgment than participants without a definition. Method: Two hundred sixty-one participants (psychology students, psychotherapists-in-training) were presented with case vignettes describing different acts of self-directed violence and were asked to make a classification. On the basis of randomized allocation, half of the participants received a definition of the different acts of self-directed violence, whereas the others did not. Results: Overall, 24.9% of the cases were misclassified. The presentation of a definition was not accompanied by a higher classification accuracy. Limitations: There may be issues about the validity of the case vignettes. Conclusions: The results highlight the importance of more methodological training of psychologists regarding suicidal issues.
Concurrent Precipitation Extremes Modulate the Response of Rice Transplanting Date to Preseason Temperature Extremes in China
Authors: Liu Yiqing , Liu Weihang , Li Yan , Ye Tao , Chen Shuo , Li Zitong , Sun Ran
Published: January 2023

Understanding how crop phenology responds to climate change is critical for enabling agricultural adaptation measures. Pre‐season temperature alone leads to well‐understood changes in crop phenology. Nevertheless, the modulation effect of concurrent precipitation extremes on the response to temperature extremes has been largely under‐addressed. Here, we investigate the response of rice transplanting dates to pre‐season temperature extremes and reveal the modulation effects of concurrent precipitation extremes by using station‐observed rice transplanting dates from 1981 to 2018 across mainland China. We also evaluate the performance of a remotely sensed phenology product, ChinaCropPhen1km, in reproducing the above temperature responses and modulation effects. Our results showed that transplanting dates tended to advance in response to an extremely hot pre‐season, while concurrent extreme drought offset the advance by up to 2.6 days. Transplanting dates tended to be delayed in response to an extremely cold pre‐season, while concurrent extreme precipitation exacerbated the delay by up to 1 day. Responses to temperature extremes and modulation effects were divergent across different regions. Under extremely hot conditions, transplanting dates advanced further in hotter and wetter regions, while under extremely cold pre‐seasons, transplanting dates delayed less in colder and drier regions. Transplanting dates from the ChinaCropPhen1km product underestimated the responses to temperature extremes by up to 4.7 days and detected the opposite modulation effect compared to those obtained from observations. Our results highlight that the need to improve our understanding and modeling of modulation effects of precipitation extremes on temperature–phenology relationship, which benefits the field of agriculture risk analysis and climate change adaptation.
A Gradient Based Subgrid‐Scale Parameterization for Ocean Mesoscale Eddies
Authors: Khani Sina , Dawson Clinton N.
Published: January 2023

Mesoscale eddies play an important role in transport of heat and biogeochemical tracers in the global ocean circulation. Resolving these energetic eddies, however, is challenging in ocean general circulation models (OGCM) because it requires a horizontal grid spacing of ≲1/8° that is computationally expensive. As a result, we are required to parameterize mesoscale eddy effects on large‐scale ocean flows. In this work, we introduce a new subgrid‐scale (SGS) model that is developed based on a Taylor series expansion of resolved variables to parameterize subgrid mesoscale eddy transports and momentum fluxes in OGCM. We have performed an a priori study to evaluate the performance of our new gradient model using high‐resolution ocean simulations. Our results show that the gradient model well predicts the actual SGS thickness fluxes in the zonal and meridional directions in coarse‐resolution simulations with the grid spacing ≳1/4°. The unresolved kinetic energy at the ocean surface is also skillfully estimated. More importantly, unlike current mesoscale eddy parameterizations, which are mainly developed based on an assumption of flat bottom ocean, our new SGS model can capture the structure of unresolved standing meanders at the ocean surface. We have also developed a dynamic procedure for setting in non‐dimensional parameters in our new parameterization through a non‐ad hoc and tuning‐free method. Overall, this work suggests that implementing the gradient model in OGCM can improve the model accuracy with an affordable computational cost in eddy‐permitting and non‐eddying simulations.
Uncertainty Decomposition to Understand the Influence of Water Systems Model Error in Climate Vulnerability Assessments
Authors: Steinschneider Scott , Herman Jonathan D. , Kucharski John , Abellera Marriah , Ruggiero Peter
Published: January 2023

Climate vulnerability assessments rely on water infrastructure system models that imperfectly predict performance metrics under ensembles of future scenarios. There is a benefit to reduced complexity system representations to support these assessments, especially when large ensembles are used to better characterize future uncertainties. An important question is whether the total uncertainty in the output metrics is primarily attributable to the climate ensemble or to the systems model itself. Here we develop a method to address this question by combining time series error models of performance metrics with time‐varying Sobol sensitivity analysis. The method is applied to a reduced complexity multi‐reservoir systems model of the Sacramento‐San Joaquin River Basin in California to demonstrate the decomposition of flood risk and water supply uncertainties under an ensemble of climate change scenarios. The results show that the contribution of systems model error to total uncertainty is small (∼5%–15%) relative to climate based uncertainties. This indicates that the reduced complexity systems model is sufficiently accurate for use in the context of the vulnerability assessment. We also observe that climate uncertainty is dominated by the choice of general circulation model and its interactive effects with the representative concentration pathway (RCP), rather than the RCP alone. This observation has implications for how climate vulnerabilities should be interpreted.
Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis
Authors: Ghareghani Majid , Pons Vincent , Laflamme Nataly , Zibara Kazem , Rivest Serge
Published: January 2023

Conflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain. Next, we showed that cuprizone-fed mice, which is an MS model, tended to have increased melatonin levels. While we used different approaches to alter the circadian rhythm of melatonin and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. Therefore, melatonin should not be considered a universal remedy, as is currently claimed. Our data emphasize the importance of monitoring melatonin/cortisol oscillations in each MS patient by considering diet and lifestyle to avoid melatonin overdose.
NCK-associated protein 1 regulates metastasis and is a novel prognostic marker for colorectal cancer
Authors: Kwon Mi Ri , Lee Jae Hee , Park Jin , Park Seok Soon , Ju Eun Jin , Ko Eun Jung , Shin Seol Hwa , Son Ga Won , Lee Hye Won , Kim Yeon Joo , Song Si Yeol , Jeong Seong-Yun , Choi Eun Kyung
Published: January 2023

Metastatic colorectal cancer (CRC) remains a substantial problem for mortality and requires screening and early detection efforts to increase survival. Epithelial-mesenchymal transition (EMT) and circulation of tumor cells in the blood play important roles in metastasis. To identify a novel target for metastasis of CRC, we conducted a gene microarray analysis using extracted RNA from the blood of preclinical models. We found that NCK-associated protein 1 (NCKAP1) was significantly increased in the blood RNA of patient-derived xenograft (PDX) models of colon cancer. In the NCKAP1 gene knockdown-induced human colon cancer cell lines HCT116 and HT29, there was a reduced wound healing area and significant inhibition of migration and invasion. As the result of marker screening for cytoskeleton and cellular interactions, CRC treated with siRNA of NCKAP1 exhibited significant induction of CDH1 and phalloidin expression, which indicates enhanced adherent cell junctions and cytoskeleton. In HCT116 cells with a mesenchymal state induced by TGFβ1, metastasis was inhibited by NCKAP1 gene knockdown through the inhibition of migration, and there was increased CTNNB1 expression and decreased FN expression. We established metastasis models for colon cancer to liver transition by intrasplenic injection shRNA of NCKAP1-transfected HCT116 cells or by implanting tumor tissue generated with the cells on cecal pouch. In metastasis xenograft models, tumor growth and liver metastasis were markedly reduced. Taken together, these data demonstrate that NCKAP1 is a novel gene regulating EMT that can contribute to developing a diagnostic marker for the progression of metastasis and new therapeutics for metastatic CRC treatment.
Significance of HLA in the development of Graves’ orbitopathy
Authors: Stasiak Magdalena , Zawadzka-Starczewska Katarzyna , Tymoniuk Bogusław , Stasiak Bartłomiej , Lewiński Andrzej
Published: January 2023

Graves’ disease (GD), similarly to most autoimmune disease, is triggered by environmental factors in genetically predisposed individuals. Particular HLA alleles increase or decrease GD risk. No such correlation was demonstrated for Graves’ orbitopathy (GO) in Caucasian population. HLA-A, -B, -C, -DQB1 and -DRB1 genotyping was performed using a high-resolution method in a total number of 2378 persons including 70 patients with GO, 91 patients with non-GO GD and 2217 healthy controls to compare allele frequencies between GO, non-GO and controls. Significant associations between GO and HLA profile were demonstrated, with HLA-A*01:01, -A*32:01, -B*37:01, -B*39:01, -B*42:01, -C*08:02, C*03:02, DRB1*03:01, DRB1*14:01 and DQB1*02:01 being genetic markers of increased risk of GO, and HLA-C*04:01, -C*03:04, -C*07:02 and -DRB1*15:02 being protective alleles. Moreover, correlations between HLA alleles and increased or decreased risk of non-GO GD, but with no impact on risk of GO development, were revealed. Identification of these groups of GO-related and GO-protective alleles, as well as the alleles strongly related to non-GO GD, constitutes an important step in a development of personalized medicine, with individual risk assessment and patient-tailored treatment.
Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia
Authors: Cheney Alexandra M. , Costello Stephanann M. , Pinkham Nicholas V. , Waldum Annie , Broadaway Susan C. , Cotrina-Vidal Maria , Mergy Marc , Tripet Brian , Kominsky Douglas J. , Grifka-Walk Heather M. , Kaufmann Horacio , Norcliffe-Kaufmann Lucy , Peach Jesse T. , Bothner Brian , Lefcort Frances , Copié Valérie , Walk Seth T.
Published: January 2023

Familial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are common among FD patients, which supports the hypothesis that the gut microbiome and metabolome are altered and dysfunctional compared to healthy individuals. Here we show significant differences in gut microbiome composition (16 S rRNA gene sequencing of stool samples) and NMR-based stool and serum metabolomes between a cohort of FD patients (~14% of patients worldwide) and their cohabitating, healthy relatives. We show that key observations in human subjects are recapitulated in a neuron-specific Elp1-deficient mouse model, and that cohousing mutant and littermate control mice ameliorates gut microbiome dysbiosis, improves deficits in gut transit, and reduces disease severity. Our results provide evidence that neurologic deficits in FD alter the structure and function of the gut microbiome, which shifts overall host metabolism to perpetuate further neurodegeneration.
Volumetric additive manufacturing of pristine silk-based (bio)inks
Authors: Xie Maobin , Lian Liming , Mu Xuan , Luo Zeyu , Garciamendez-Mijares Carlos Ezio , Zhang Zhenrui , López Arturo , Manríquez Jennifer , Kuang Xiao , Wu Junqi , Sahoo Jugal Kishore , González Federico Zertuche , Li Gang , Tang Guosheng , Maharjan Sushila , Guo Jie , Kaplan David L. , Zhang Yu Shrike
Published: January 2023

Volumetric additive manufacturing (VAM) enables fast photopolymerization of three-dimensional constructs by illuminating dynamically evolving light patterns in the entire build volume. However, the lack of bioinks suitable for VAM is a critical limitation. This study reports rapid volumetric (bio)printing of pristine, unmodified silk-based (silk sericin (SS) and silk fibroin (SF)) (bio)inks to form sophisticated shapes and architectures. Of interest, combined with post-fabrication processing, the (bio)printed SS constructs reveal properties including reversible as well as repeated shrinkage and expansion, or shape-memory; whereas the (bio)printed SF constructs exhibit tunable mechanical performances ranging from a few hundred Pa to hundreds of MPa. Both types of silk-based (bio)inks are cytocompatible. This work supplies expanded bioink libraries for VAM and provides a path forward for rapid volumetric manufacturing of silk constructs, towards broadened biomedical applications.
Stress promotes RNA G-quadruplex folding in human cells
Authors: Kharel Prakash , Fay Marta , Manasova Ekaterina V. , Anderson Paul J. , Kurkin Alexander V. , Guo Junjie U. , Ivanov Pavel
Published: January 2023

Guanine (G)-rich nucleic acids can fold into G-quadruplex (G4) structures under permissive conditions. Although many RNAs contain sequences that fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. In this report, we showed that the folding of putative rG4s in human cells into rG4 structures is dynamically regulated under stress. By using high-throughput dimethylsulfate (DMS) probing, we identified hundreds of endogenous stress-induced rG4s, and validated them by using an rG4 pull-down approach. Our results demonstrate that stress-induced rG4s are enriched in mRNA 3′-untranslated regions and enhance mRNA stability. Furthermore, stress-induced rG4 folding is readily reversible upon stress removal. In summary, our study revealed the dynamic regulation of rG4 folding in human cells and suggested that widespread rG4 motifs may have a global regulatory impact on mRNA stability and cellular stress response.
Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors
Authors: Yu Zhiyin , Huang Jian-Ping , Yang Jing , Liu Chongxi , Yan Yijun , Wang Li , Zhao Junwei , Chen Yin , Xiang Wensheng , Huang Sheng-Xiong
Published: January 2023

Angiotensin-converting enzyme inhibitors are widely used for treatment of hypertension and related diseases. Here, six karnamicins E1-E6 (1–6), which bear fully substituted hydroxypyridine and thiazole moieties are characterized from the rare actinobacterium Lechevalieria rhizosphaerae NEAU-A2. Through a combination of isotopic labeling, genome mining, and enzymatic characterization studies, the programmed assembly of the fully substituted hydroxypyridine moiety in karnamicin is proposed to be due to sequential operation of a hybrid polyketide synthase-nonribosomal peptide synthetase, two regioselective pyridine ring flavoprotein hydroxylases, and a methyltransferase. Based on AlphaFold protein structures predictions, molecular docking, and site-directed mutagenesis, we find that two pyridine hydroxylases deploy active site residues distinct from other flavoprotein monooxygenases to direct the chemo- and regioselective hydroxylation of the pyridine nucleus. Pleasingly, karnamicins show significant angiotensin-converting enzyme inhibitory activity with IC50 values ranging from 0.24 to 5.81 μM, suggesting their potential use for the treatment of hypertension and related diseases.
Near-infrared-IIb emitting single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown after traumatic brain injury
Authors: Huang Biao , Tang Tao , Chen Shi-Hui , Li Hao , Sun Zhi-Jun , Zhang Zhi-Lin , Zhang Mingxi , Cui Ran
Published: January 2023

The blood-brain barrier breakdown, as a prominent feature after traumatic brain injury, always triggers a cascade of biochemical events like inflammatory response and free radical-mediated oxidative damage, leading to neurological dysfunction. The dynamic monitoring the status of blood-brain barrier will provide potent guidance for adopting appropriate clinical intervention. Here, we engineer a near-infrared-IIb Ag2Te quantum dot-based Mn single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown of mice after traumatic brain injury. The dynamic change of blood-brain barrier, including the transient cerebral hypoperfusion and cerebrovascular damage, could be resolved with high spatiotemporal resolution (150 ms and ~ 9.6 µm). Notably, the isolated single Mn atoms on the surface of Ag2Te exhibited excellent catalytic activity for scavenging reactive oxygen species to alleviate neuroinflammation in brains. The timely injection of Mn single-atom catalyst guided by imaging significantly promoted the reconstruction of blood-brain barrier and recovery of neurological function after traumatic brain injury.
Force-induced ion generation in zwitterionic hydrogels for a sensitive silent-speech sensor
Authors: Xu Sijia , Yu Jie-Xiang , Guo Hongshuang , Tian Shu , Long You , Yang Jing , Zhang Lei
Published: January 2023

Human-sensitive mechanosensation depends on ionic currents controlled by skin mechanoreceptors. Inspired by the sensory behavior of skin, we investigate zwitterionic hydrogels that generate ions under an applied force in a mobile-ion-free system. Within this system, water dissociates as the distance between zwitterions reduces under an applied pressure. Meanwhile, zwitterionic segments can provide migration channels for the generated ions, significantly facilitating ion transport. These combined effects endow a mobile-ion-free zwitterionic skin sensor with sensitive transduction of pressure into ionic currents, achieving a sensitivity up to five times that of nonionic hydrogels. The signal response time, which relies on the crosslinking degree of the zwitterionic hydrogel, was ~38 ms, comparable to that of natural skin. The skin sensor was incorporated into a universal throat-worn silent-speech recognition system that transforms the tiny signals of laryngeal mechanical vibrations into silent speech.
Coupled induction of prophage and virulence factors during tick transmission of the Lyme disease spirochete
Authors: Wachter Jenny , Cheff Britney , Hillman Chad , Carracoi Valentina , Dorward David W. , Martens Craig , Barbian Kent , Nardone Glenn , Renee Olano L. , Kinnersley Margie , Secor Patrick R. , Rosa Patricia A.
Published: January 2023

The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochetes in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18-depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete.
Interbasin water transfers in the United States and Canada
Authors: Siddik Md. Abu Bakar , Dickson Kerim E. , Rising James , Ruddell Benjamin L. , Marston Landon T.
Published: January 2023

Interbasin water transfers (IBTs) can have a significant impact on the environment, water availability, and economies within the basins importing and exporting water, as well as basins downstream of these water transfers. The lack of comprehensive data identifying and describing IBTs inhibits understanding of the role IBTs play in supplying water for society, as well as their collective hydrologic impact. We develop three connected datasets inventorying IBTs in the United States and Canada, including their features, geospatial details, and water transfer volumes. We surveyed the academic and gray literature, as well as local, state, and federal water agencies, to collect, process, and verify IBTs in Canada and the United States. Our comprehensive IBT datasets represent all known transfers of untreated water that cross subregion (US) or subdrainage area (CA) boundaries, characterizing a total of 641 IBT projects. The infrastructure-level data made available by these data products can be used to close water budgets, connect water supplies to water use, and better represent human impacts within hydrologic and ecosystem models.
Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients
Authors: Ohashi Yuki , Toyoda Masao , Saito Nobumichi , Koizumi Masahiro , Kanai Genta , Komaba Hirotaka , Kimura Moritsugu , Wada Takehiko , Takahashi Hiroo , Takahashi Yuichiro , Ishida Naoto , Kakuta Takatoshi , Fukagawa Masafumi , Ichida Kimiyoshi
Published: January 2023

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.
Engineered nanovesicles from stromal vascular fraction promote angiogenesis and adipogenesis inside decellularized adipose tissue through encapsulating growth factors
Authors: Tu Jun , Zeng Yuyang , An Ran , Sun Jiaming , Wen Huicai
Published: January 2023

Acellular matrix is a commonly used biomaterial in the field of biomedical engineering and revascularization is the key process to affect the effect of acellular matrix on tissue regeneration. The application of bioactive factors related to angiogenesis has been popular in the regulation of revascularization, but the immune system clearance, uncontrollable systemic reactions, and other factors make this method face challenges. Recent reports showed that engineered cells into nanovesicles can reorganize cell membranes and encapsulate cellular active factors, extending the in vitro preservation of cytokines. However, the problems of exogenous biological contamination and tumorigenicity restricted the clinical transformation and wide application of this method. Here, we for the first time engineer stromal vascular fraction (SVF) which is extracted from fat into nanovesicles (SVF-EVs) for angiogenesis in the acellular matrix. SVF-EVs not only promote the migration of vascular endothelial cells in vitro, but also facilitate the lipogenic differentiation of mesenchymal stem cells. In vivo, SVF-EVs enhanced the retention of decellularized adipose tissue after transplanting to the subcutaneous area of nude mice. Immunofluorescence staining further showed that SVF-EVs promoted the formation of vascular networks with large lumen diameter in the grafted acellular matrix, accompanied by adipocyte regeneration peripherally. These findings reveal that SVF-EVs can be a viable method for accelerating revascularization in acellular matrix, and this process of squeezing tissue into nanovesicles shows the potential for rapid clinical transformation.
Impact of the adjunctive use criteria for intravascular ultrasound-guided percutaneous coronary intervention and clinical outcomes
Authors: Suwannasom Pannipa , Chichareon Ply , Roongsangmanoon Worawut , Thongtanomkul Artit , Wongpen Anuchit , Muenkaew Muenpetch , Kanoksilp Anek , Chandavimol Mann , Kuanprasert Srun , Thakkinstian Ammarin , Srimahachota Suphot , Sansanayudh Nakarin
Published: January 2023

The impact of the adherence to the adjunctive use criteria (AUC) for intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI) and clinical outcomes in low IVUS volume countries are limited. The current study compared the procedural success and complication rates between used and not used IVUS catheter in the patients who were met (C +) and were not met (C−) the AUC for IVUS-guided PCI. From June 2018 through June 2019, a total of 21,066 patients were included in the Thai PCI registry. Among the study population, 15,966 patients (75.8%) have met the IVUS-AUC. The IVUS-guided PCI rates were 14.5% and 11.3% in the C + and C − groups, respectively. After adjusting for covariables by propensity model, IVUS-guided PCI was identified as an independent predictor of the procedural success rate regardless of whether the AUC were met with the relative risk [RR (95% confidence interval (CI)] of 1.033(1.026–1.040) and 1.012(1.002–1.021) in C + and C− groups, respectively. IVUS-guided PCI increased the procedural complication risks in both groups but were not significant with corresponding RRs of 1.171(0.915–1.426) and 1.693(0.959–2.426). Procedural success was achieved with IVUS-guided PCI regardless of whether the AUC were met. IVUS-guided PCI did not lead to an increase in procedural complications.
Relationship between serum nitric oxide of patients with thyroid disorders and metabolic syndrome indices and nitrate concentration of water
Authors: Jafari Shaghayegh , Dehghani Mansooreh , Ghaem Haleh , Soveid Mahmood , Hashemi Hasan
Published: January 2023

This case–control study aimed to assess the effect of drinking water nitrate on serum nitric oxide concentration and the risk of metabolic syndrome (MetS) in the population in the Middle East. The study included 50 control and 50 thyroid disorder cases who were referred to two medical centers in 2021. In this study, serum nitric oxide concentration, drinking water nitrate, and metabolic syndrome components were measured in the two groups. The results showed there was a statistically significant difference between serum NO in the case and control groups (p-value < 0.001). There was a positive correlation between the concentration of nitrate in drinking water and serum nitric oxide in the case and control groups; however, this relationship was not significant statistically. A statistically significant difference was found between serum nitric oxide and systolic blood pressure in the cases (p-value < 0.05), but there was no significant difference between MetS and nitric oxide. Therefore, we concluded that the relationship between nitric oxide and nitrate in consuming water should be determined in thyroid patients. In addition to their water consumption, it is better to study the nitrate of foods, especially vegetables.
Detection of H2S, HF and H2 pollutant gases on the surface of penta-PdAs2 monolayer using DFT approach
Authors: Raval Dhara , Gupta Sanjeev K. , Gajjar P. N.
Published: January 2023

In this research, the adsorption of targeted noxious gases like H2S, HF and H2on penta-PdAs2monolayer are deeply studied by means of the density functional theory (DFT). After the capturing of three kind of pollutant gases (H2S, HF and H2), it is observed that, the electronic properties are slightly affected from the pristine one. In all cases, the physisorption interaction found with adsorption energy of − 0.49, − 0.39 and − 0.16 eV for H2S, HF and H2gases, respectively. Which is exposed that H2S gas strongly absorbed on penta-PdAs2nanosheet. In case of HF (H2) gas adsorbed systems, the obtained charge transfer is + 0.111 e (+ 0.037 e), revealed that the electrons are going to PdAs2nanosheet from the HF (H2) molecules. Further, under the non-equilibrium Green’s function (NEGF) theory, the IV response and sensitivity of absorbed H2S, HF and H2have been discussed. The results demonstrate that the H2S molecules on PdAs2has suitable adsorption strength and explicit charge transfer compared with other targeted molecules. Hence, our novel findings of H2S, HF and H2targeted gas sensing on penta-PdAs2nanosheet might provide reference-line to design modern gas sensor device at the nano-scale.
Betulinaldehyde exhibits effective anti-tumor effects in A549 cells by regulating intracellular autophagy
Authors: Huang Pan-hao , Duan Xiang-bing , Tang Zi-zhao , Zou Zhen-xing , Song Wen-min , Gao Ge , Li Dai , Nie Fang-qin , Yan Xin , Fu Yang-xia , Guo Ren , Xu Yan-ying
Published: January 2023

It is of great significance to find new effective drugs for an adjuvant therapy targeting lung cancer to improve the survival rate and prognosis of patients with the disease. Previous studies have confirmed that certain Chinese herbal extracts have clear anti-tumor effects, and in our preliminary study, betulinaldehyde was screened for its potential anti-tumor effects. The current study thus aimed to confirm the anti-tumor effect of betulinaldehyde, using in vitro experiments to explore its underlying molecular mechanism. It was found that betulinaldehyde treatment significantly inhibited the viability, proliferation, and migration of A549 cells in a dose-dependent manner. In addition, betulinaldehyde inhibited the activation of Akt, MAPK, and STAT3 signaling pathways in A549 cells in a time-dependent manner. More importantly, betulinaldehyde also decreased the expression level of SQSTM1 protein, increased the expression level of LC3 II, and increased the autophagy flux in A549 cells. The pretreatment of A549 cells with the autophagy inhibitor, 3-methyladenine, could partially negate the anti-tumor effects of betulinaldehyde. These findings suggest that betulinaldehyde could significantly inhibit the oncological activity of A549 cells by regulating the intracellular autophagy level, making it a potentially effective option for the adjuvant therapy used to treat lung cancer in the future.
Device simulations with A U-Net model predicting physical quantities in two-dimensional landscapes
Authors: Lee Wen-Jay , Hsieh Wu-Tsung , Fang Bin-Horn , Kao Kuo-Hsing , Chen Nan-Yow
Published: January 2023

Although Technology Computer-Aided Design (TCAD) simulation has paved a successful and efficient way to significantly reduce the cost of experiments under the device design, it still encounters many challenges as the semiconductor industry goes through rapid development in recent years, i.e. Complex 3D device structures, power devices. Recently, although machine learning has been proposed to enable the simulation acceleration and inverse‑design of devices, which can quickly and accurately predict device performance, up to now physical quantities (such as electric field, potential energy, quantum-mechanically confined carrier distributions, and so on) being essential for understanding device physics can still only be obtained by traditional time-consuming self-consistent calculation. In this work, we employ a modified U-Net and train the models to predict the physical quantities of a MOSFET in two-dimensional landscapes for the first time. Errors in predictions by the two models have been analyzed, which shows the importance of a sufficient amount of data to prediction accuracy. The computation time for one landscape prediction with high accuracy by our well-trained U-Net model is much faster than the traditional approach. This work paves the way for interpretable predictions of device simulations based on convolutional neural networks.