bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the utilization of technological factors to promote e-commerce adoption in small and medium enterprises
Authors: Hossain Md Billal , Dewan Nargis , Senin Aslan Amat , Illes Csaba Balint
Published: March 2023

This study examined the technological factor's utilization to promote the e-commerce in small and medium sized enterprises in Bangladesh. The technological factors are, Information and communication adoption, Internet connectivity, and Business data management. The e-commerce adoption factors involve the strategic innovation, research and development activity, and Productivity growth. The electronic commerce is being widely adopted in Bangladesh in the time of covid-19 pandemic. In the adoption of e-commerce, prominent factors are the internet connectivity, which plays a major role and Business data management which has equal importance for SMEs. SMEs have limited access to data as compared to multinational industries. However, the data has equal importance for multinational and SMEs to improve the e-commerce business. The research collects data from 115 SMEs from Bangladesh relating to different fields. The random selection method has been advised to collect data from SMEs aged not less than five years. The data collected for this research is through the interested parties of small and medium sized enterprises in Bangladesh. The data of the research is interpreted and analyzed through statistical software SPSS.
Longitudinal Modeling of Age-Dependent Latent Traits with Generalized Additive Latent and Mixed Models
Authors: Sørensen Øystein , Fjell Anders M. , Walhovd Kristine B.
Published: March 2023

We present generalized additive latent and mixed models (GALAMMs) for analysis of clustered data with responses and latent variables depending smoothly on observed variables. A scalable maximum likelihood estimation algorithm is proposed, utilizing the Laplace approximation, sparse matrix computation, and automatic differentiation. Mixed response types, heteroscedasticity, and crossed random effects are naturally incorporated into the framework. The models developed were motivated by applications in cognitive neuroscience, and two case studies are presented. First, we show how GALAMMs can jointly model the complex lifespan trajectories of episodic memory, working memory, and speed/executive function, measured by the California Verbal Learning Test (CVLT), digit span tests, and Stroop tests, respectively. Next, we study the effect of socioeconomic status on brain structure, using data on education and income together with hippocampal volumes estimated by magnetic resonance imaging. By combining semiparametric estimation with latent variable modeling, GALAMMs allow a more realistic representation of how brain and cognition vary across the lifespan, while simultaneously estimating latent traits from measured items. Simulation experiments suggest that model estimates are accurate even with moderate sample sizes.
Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction
Authors: Jonsson William O. , Borowik Agnieszka K. , Pranay Atul , Kinter Michael T. , Mirek Emily T. , Levy Jordan L. , Snyder Elizabeth M. , Miller Benjamin F. , Anthony Tracy G.
Published: March 2023

Dietary sulfur amino acid restriction (SAAR) protects against diet-induced obesity, extends healthspan, and coincides with an overall reduction in hepatic protein synthesis. To explore the underpinnings of SAAR-induced slowed growth and its impact on liver metabolism and proteostasis, we resolved changes in hepatic mRNA and protein abundances and compared synthesis rates of individual liver proteins. To achieve this, adult male mice were provided deuterium-labeled drinking water while freely consuming either a regular-fat or high-fat diet that was SAA restricted. Livers from these mice and their respective dietary controls were used to conduct transcriptomic, proteomic, and kinetic proteomic analyses. We found that remodeling of the transcriptome by SAAR was largely agnostic to dietary fat content. Shared signatures included activation of the integrated stress response alongside alterations in metabolic processes impacting lipids, fatty acids, and amino acids. Changes to the proteome correlated poorly with the transcriptome, and yet, functional clustering of kinetic proteomic changes in the liver during SAAR revealed that the management of fatty acids and amino acids were altered to support central metabolism and redox balance. Dietary SAAR also strongly influenced the synthesis rates of ribosomal proteins and ribosome-interacting proteins regardless of dietary fat. Taken together, dietary SAAR alters the transcriptome and proteome in the liver to safely manage increased fatty acid flux and energy use and couples this with targeted changes in the ribo-interactome to support proteostasis and slowed growth.
#Sponseredathlete: the marketing of image and performance enhancing drugs on Facebook and Instagram
Authors: Gibbs Nick
Published: March 2023

This article sets out to investigate the marketing of image and performance enhancing drugs (IPEDs) on the social media platforms Facebook and Instagram. Drawing upon a ‘connective’ ethnographic exploration of IPED use and supply, the paper first outlines a supplier typology on these platforms, before shedding light on the marketing strategies employed by sellers in order to overcome the inherent distrust of online sales and build a trustworthy brand. Techniques identified include athlete sponsorship, the sharing of bodybuilding fitspiration content, self-objectification, posting images showcasing transformation photos and customer feedback, and seasonal sales and promotions. Analysis encompasses the centrality of product branding, the overlaps between licit and illicit market advertising strategies, and the affordances of the platforms under study. Finally, conclusions relating to the implications of these findings to scholarship, policy, and regulation are offered.
Metabolic dysfunction–associated fatty liver disease (MAFLD): an update of the recent advances in pharmacological treatment
Authors: Sangro Paloma , de la Torre Aláez Manuel , Sangro Bruno , D’Avola Delia
Published: March 2023

Metabolic dysfunction–associated fatty liver disease (MAFLD) is nowadays considered the liver manifestation of metabolic syndrome. Its prevalence is increasing worldwide in parallel to the epidemic of diabetes and obesity. MAFLD includes a wide spectrum of liver injury including simple steatosis and non-alcoholic steatohepatitis (NASH) that may lead to serious complications such as liver cirrhosis and liver cancer. The complexity of its pathophysiology and the intricate mechanisms underlying disease progression explains the huge variety of molecules targeting diverse biological mechanisms that have been tested in preclinical and clinical settings in the last two decades. Thanks to the large number of clinical trials of the last few years, most of them still ongoing, the pharmacotherapy scenario of MAFLD is rapidly evolving. The three major components of MAFLD, steatosis, inflammation, and fibrosis seem to be safely targeted with different agents at least in a large proportion of patients. Likely, in the next few years more than one drug will be approved for the treatment of MAFLD at different disease stages. The aim of this review is to synthesize the characteristics and the results of the most advanced clinical trials for the treatment of NASH to evaluate the recent advances of pharmacotherapy in this disease.
LDP and CLT for SPDEs with transport noise
Authors: Galeati Lucio , Luo Dejun
Published: March 2023

In this work we consider solutions to stochastic partial differential equations with transport noise, which are known to converge, in a suitable scaling limit, to solution of the corresponding deterministic PDE with an additional viscosity term. Large deviations and Gaussian fluctuations underlying such scaling limit are investigated in two cases of interest: stochastic linear transport equations in dimension$$D\ge 2$$D≥2and 2D Euler equations in vorticity form. In both cases, a central limit theorem with strong convergence and explicit rate is established. The proofs rely on nontrivial tools, like the solvability of transport equations with supercritical coefficients and$$\Gamma $$Γ-convergence arguments.
Effect of targeted intervention on C-terminal agrin fragment and its association with the components of sarcopenia: a scoping review
Authors: Kumar Prabal , Nayak Kusumakshi , Umakanth Shashikiran , Girish N.
Published: March 2023

Background

C-terminal Agrin Fragment (CAF) has emerged as a potent biomarker for identifying sarcopenia. However, the effect of interventions on CAF concentration and the association of CAF with sarcopenia components are unclear.

Objective

To review the association between CAF concentration and muscle mass, muscle strength, and physical performance among individuals with primary and secondary sarcopenia and to synthesize the effect of interventions on the change in the level of CAF concentration.

Methods

A systematic literature search was conducted in six electronic databases, and studies were included if they met the selection criteria decided a priori. The data extraction sheet was prepared, validated, and extracted relevant data.

Results

A total of 5,158 records were found, of which 16 were included. Among studies conducted on individuals with primary sarcopenia, muscle mass was significantly associated with CAF levels, followed by hand grip strength (HGS) and physical performance, with more consistent findings in males. While in secondary sarcopenics, the strongest association was found for HGS and CAF levels, followed by physical performance and muscle mass. CAF concentration was reduced in trials that used functional, dual task, and power training, whereas resistance training and physical activity raised CAF levels. Hormonal therapy did not affect serum CAF concentration.

Conclusion(s)

The association between CAF and sarcopenic assessment parameters varies in primary and secondary sarcopenics. The findings would help practitioners and researchers choose the best training mode/parameters/exercises to reduce CAF levels and, eventually, manage sarcopenia.
Structure, Property, and Performance of Catalyst Layers in Proton Exchange Membrane Fuel Cells
Authors: Zhao Jian , Liu Huiyuan , Li Xianguo
Published: March 2023

Catalyst layer (CL) is the core component of proton exchange membrane (PEM) fuel cells, which determines the performance, durability, and cost. However, difficulties remain for a thorough understanding of the CLs’ inhomogeneous structure, and its impact on the physicochemical and electrochemical properties, operating performance, and durability. The inhomogeneous structure of the CLs is formed during the manufacturing process, which is sensitive to the associated materials, composition, fabrication methods, procedures, and conditions. The state-of-the-art visualization and characterization techniques are crucial to examine the CL structure. The structure-dependent physicochemical and electrochemical properties are then thoroughly scrutinized in terms of fundamental concepts, theories, and recent progress in advanced experimental techniques. The relation between the CL structure and the associated effective properties is also examined based on experimental and theoretical findings. Recent studies indicated that the CL inhomogeneous structure also strongly affects the performance and degradation of the whole fuel cell, and thus, the interconnection between the fuel cell performance, failure modes, and CL structure is comprehensively reviewed. An analytical model is established to understand the effect of the CL structure on the effective properties, performance, and durability of the PEM fuel cells. Finally, the challenges and prospects of the CL structure-associated studies are highlighted for the development of high-performing PEM fuel cells.

Graphical abstract
Characteristics of older cyclists with self-perceived needs for improvement in cycling competence: SiFAr trial
Authors: Keppner Veronika , Sieber Cornel C. , Freiberger Ellen , Kob Robert , Krumpoch Sebastian , Siebentritt Hanna M.
Published: March 2023

Background

Older cyclists are in great risk of being injured or killed in a traffic-related accident and their needs should find more consideration in safety guidelines, urban planning, and future intervention programs.

Objective

The aim for this cross-sectional analysis was to comprehensively explore characteristics of community-dwelling cyclists aged 65 years and older with a self-perceived need to increase cycle competence.

Methods

118 older adults (mean age 73.3 ± 5.2 years, 61% women) performed a standardized cycle course representing specific cycling skills. Additionally, health and functional assessments were carried out and characteristics regarding demographic, health, falls, bicycle equipment/type and cycling biography/behavior were obtained.

Results

The majority (67.8%) of this community-dwelling adults reported being unsafe when cycling and 41.3% had a bicycle fall in the past year. More than half of the participants showed at least one limitation in each of the measured cycling skills. Women significantly had more frequent limitations in four of the cycling skills measured (p ≤ 0.001) compared to men. While no significant differences were found for falls, health and functional characteristics, women and men differed significantly in terms of bicycle type, equipment, and perceived safety (p < 0.001).

Conclusion

Limitations in cycling should be compensated by preventive bicycle training and a safe cycling infrastructure. Bicycle fit, the wearing of bicycle helmets and promotion of a sense of security while cycling can further reduce accident risk and must find recognition in safety guidelines. In addition, educational initiatives have to dismantle gender-related bicycle stereotypes.
Transcriptome reveals the molecular mechanism of chaetoviridin A inhibiting the spore germination of Verticillium dahliae
Authors: Zhang Yun , Yang Yuanxue , Wang Aiyu , Xue Chao , Zhao Ming , Zhang Jianhua
Published: March 2023

The pathogen Verticillium dahliae causes Verticillium wilt in a number of crops, including cotton Verticillium wilt. Chaetoviridin A, a secondary metabolite of Chaetomium globosum, significantly inhibits the growth of V. dahliae. Spore germination is a major part of the disease cycle. However, the molecular mechanism of chaetoviridin A inhibiting spore germination of V. dahliae is unknown. In this work, we found that chaetoviridin A significantly inhibited spore germination of V. dahliae. Transcriptome analysis showed that DEGs were enriched in linolenic acid metabolism, alpha-Linolenic acid metabolism, Arachidonic acid metabolism and Purine metabolism pathways at 1 h, which were related to cell membrane. At 3 h, DEGs were enriched in the pathways of galactose metabolism, diterpenoid biosynthesis, cysteine and methionine metabolism, and starch and sucrose metabolism, which were mainly related to amino acid metabolism and sugar metabolism. Several genes related to glucose metabolism were identified, mainly including Glucagon endo-1,3-alpha-glucosidase agn1, glucoamylase, maltose O-acetyltransferase, and beta-galactosidase. Stress resistance gene PAL, detoxification gene P450 2C31 and ABA receptor were also down- regulated. These genes may be related to spore germination. These results provide a theoretical basis for chaetoviridin A to control fungal diseases.
Assessment of the influence of soil inoculation on changes in the adaptability of maize hybrids
Authors: Kálmán Csaba Dániel , Kálmán László , Szél Sándor , Mórocz Salamon Katalin , Nagy Zoltán , Kiss Erzsébet , Posta Katalin
Published: March 2023

The aim of this paper is to present the results of the field trial carried out to collect and assess data on the interaction of maize (Zea mays L) genotypes and beneficial microorganisms. The small plot field trial consisting of untreated control plots and plots treated with biostimulants was conducted in three consecutive years (2019, 2020 and 2021). Yield is a particularly important trait from the aspect of maize breeding as well as maize production; therefore, the present study focused more closely on how it was influenced by the biostimulant treatments. The level of grain yield, grain moisture content at harvest and grain dry-matter content were observed and recorded as the components of yield. The nutritional value of kernels was also tested, and protein, oil and starch contents were analysed as the most important components of this trait. The results reflected that the treatment with biostimulants constituted from beneficial microorganisms can be listed among the factors influencing the grain yield, in addition to the seasonal effect, the genotype and the nutrient supply of the soil. The treatment with biostimulants, even on its own among the factors, had an impact on the quantity and components of yield, and on the characteristics determining the kernel nutritional value. The interaction between the genotypes and the interacting microorganisms is of specific importance. The most spectacular result was attained with the application of one of the biostimulants leading to elevated grain yield in 75% of the maize genotypes in the study, along with a kernel nutritive value equal to the control group over all of the three years of the trial.
AI, the beauty of places, and the metaverse: beyond “geometrical fundamentalism”
Authors: Lavdas Alexandros A. , Mehaffy Michael W. , Salingaros Nikos A.
Published: March 2023

As the tech world moves increasingly toward an AI-generated virtual universe — the so-called “metaverse” — new paradigms define the impacts of this technology on its human users. AI and VR, like the Internet before them, offer both remarkable opportunities and pitfalls. Virtual Reality constitutes a new kind of human environment, and experiencing it relies upon human neurological mechanisms evolved to negotiate — and survive in — our ancestral physical environments. Despite the unrestricted freedom of designing the virtual universe, interacting with it is affected strongly by the body’s built-in physiological and psychological constraints. The eventual success of the metaverse will be determined by how successfully its designers manage to accommodate unconscious mechanisms of emotional attachment and wellbeing. Some fundamental misunderstandings coming from antiquated design models have influenced virtual environmental structures. It is likely that those design decisions may be handicapping the metaverse’s ultimate appeal and utility.
Looking to the Horizon: The Meanings of Reparations for Unbearable Crises
Authors: Riley Case Sarah
Published: March 2023

Harms that arise from climate catastrophes deepen already unbearable forms of racial oppression. Both can be traced to accumulative ways of life that justified slavery and colonialism, which shifted into new forms of hegemony under liberal international law. A growing response has been to demand reparations. However, the meanings of reparations are vast and sometimes counterintuitive. This essay reflects on reparations claims emanating from the Caribbean, as one place where race and ecology converge. The Caribbean was forged by Indigenous genocide, the enslavement of African peoples, and the indentured labor of Asian peoples. Today, descendants in the region face subordination under liberal international law and climate catastrophes. Such conditions reveal that reparations are foremost a horizon of transformation away from accumulative ways of life that spread from Europe to the world, structuring the present reality. “Reparations” also refers to immediate justices that meet the demands of those who are harmed, because this prefigures the horizon of transformation by disrupting imperialism. These qualities dispel racializing critiques from the First World that reparations are irrational, or constitute politics separate from law. Reparations can enact legal relations that are meaningful to those “on the bottom,” and emancipatory for everyone, when communities and social movements define them.
Beyond Color-Blind International Economic Law
Authors: Gathii James Thuo
Published: March 2023

This essay makes three claims. First, that the central role of race in international economic law has been erased and much more needs to be done to recover its large footprints in the discipline as well as in the policies and practices that constitute it. Second, that rules of international economic law formally embed racially constructed hierarchies, such as those that subordinate the status of former and current colonies. Further, that this subordination is not merely of the former and current colonies, but also of large swaths of Black and Brown peoples around the world. Third, that international economic law in both the Global North and the Global South has played a key role in the cultural production of racist tropes that justify the continued servitude of the former and current colonies. This subordination ensures that returns to capital serve a small minority of wealthy individuals and corporate entities at the expense of large segments of humanity, particularly Black and Brown peoples.
Whitelashing: Black Politicians, Taxes, and Violence
Authors: Logan Trevon D.
Published: March 2023

This paper provides the first evidence of the effect of tax policy on violent attacks against Black politicians. I find a positive effect of local tax revenue on subsequent violence against Black politicians. A dollar increase in per capita county taxes in 1870 increased the likelihood of a violent attack by more than 25 percent. The result is robust to controls for numerous economic, historical, and political factors. I also find counties where Black officeholders were attacked have the largest tax reversions. This provides the first quantitative evidence that Reconstruction political violence was specifically related to Black political efficacy.
Lasertechniken in der Behandlung des benignen Prostatasyndroms
Authors: Brinkmann Isabel , Schott Melanie , Keller Patrick , Tamalunas Alexander , Atzler Michael , Ebner Benedikt , Stief Christian G. , Magistro Giuseppe
Published: March 2023

Zusammenfassung: Laser haben ein umfangreiches Anwendungsspektrum in der endourologischen Therapie. Nicht nur in der Therapie von Steinen, auch in der Behandlung des benignen Prostatasyndroms (BPS) nimmt ihr Stellenwert immer weiter zu. Auf die endourologische Behandlung der BPS mit verschiedenen Laser-Techniken wird im weiteren Verlauf näher eingegangen. Dabei werden zuerst die physikalischen Unterschiede der einzelnen Laser erklärt, im weiteren Verlauf die Behandlungsmöglichkeiten an sich, die mit einem Laser durchgeführt werden können. Hauptaugenmerk soll auf dem konkreten Vergleich der Behandlungsmethoden vor allem im klinischen Kontext liegen. Insbesondere die OP-Dauer, Hospitalisierungsdauer, das Nachblutungsrisiko, die DK(Dauerkatheter)-Zeit, das Risiko eines Harnverhalts und das Risiko für postoperative Komplikationen wie retrograde Ejakulation, BH (Blasenhals)-Sklerose, HR (Harnröhren)-Striktur, Adenomrezidive sollen für die wichtigsten Methoden aufgeführt und miteinander verglichen werden. Dennoch liegt weiterhin die Verteilung von TURP zu Laser mit 30:1 zu Gunsten der TURP [1].
Laparoskopisch roboterassistierte Adenomenukleation der Prostata
Authors: Burkhardt Orlando , Padevit Christian , John Hubert
Published: March 2023

Zusammenfassung: Die operative Behandlung grosser Prostataadenome (> 80g) bei Männern mit symptomatischer Prostatahyperplasie und Therapieversagen mit einem Alphablocker ist eine Herausforderung im klinisch urologischen Alltag. Der operative Goldstandard, die transurethrale Elektroresektion der Prostata (TUR-P) ist aufgrund verlängerter Resektionszeiten bei grossen Adenomen und der damit vergesellschafteten erhöhten Komplikationsraten zur Behandlung ungeeignet. Über Jahrzehnte hinweg wurden grosse Adenome mittels offener Prostataadenomenukleation behandelt. Die Technik ist zum Teil nach wie vor noch etabliert, jedoch mit erheblichen Morbiditäts- und Komplikationsraten behaftet. Vor diesem Hintergrund wurden in den letzten Jahren zahlreiche minimal invasive Techniken entwickelt. Diese beinhalten transurethrale Interventionen, hauptsächlich mit Anwendung von Lasertechnologien, wie die Holmium-Laser-Enukleation (HoLEP) oder die KTP-Laser-Vaporisation (Greenlight™-Laser). Zudem wurden die sehr früh beschriebenen offenen Enukleationstechniken konventionell laparoskopisch und schliesslich auch laparoskopisch roboterassistiert angewandt, evaluiert und weiterentwickelt. Mittlerweile ist die laparoskopisch roboterassistierte Adenomenukleation der Prostata (RASP) und insbesondere die Modifikation mittels extraperitonealem extravesikalem Zugang und intraprostatischer Rekonstruktion der Urethra (EE-RASP) zur Ausschaltung des offenliegenden Wundbettes aus dem Harntrakt mit konsekutiv deutlicher Reduktion der perioperativen Komplikationen, eine etablierte Methode und eine Alternative der neueren transurethralen Methoden.
From the Surface Ocean to the Seafloor: Linking Modern and Paleo‐Genetics at the Sabrina Coast, East Antarctica (IN2017_V01)
Authors: Armbrecht Linda , Focardi Amaranta , Lawler Kelly‐Anne , O’Brien Phil , Leventer Amy , Noble Taryn L. , Opdyke Bradley , Duffy Meghan , Evangelinos Dimitris , George Simon C. , Lieser Jan , López‐Quirós Adrián , Post Alix , Ostrowski Martin , Paulsen Ian , Armand Leanne
Published: March 2023

With ongoing climate change, research into the biological changes occurring in particularly vulnerable ecosystems, such as Antarctica, is critical. The Totten Glacier region, Sabrina Coast, is currently experiencing some of the highest rates of thinning across all East Antarctica. An assessment of the microscopic organisms supporting the ecosystem of the marginal sea‐ice zone over the continental rise is important, yet there is a lack of knowledge about the diversity and distribution of these organisms throughout the water column, and their occurrence and/or preservation in the underlying sediments. Here, we provide a taxonomic overview of the modern and ancient marine bacterial and eukaryotic communities of the Totten Glacier region, using a combination of 16S and 18S rRNA amplicon sequencing (modern DNA) and shotgun metagenomics (sedimentary ancient DNA, sedaDNA). Our data show considerable differences between eukaryote and bacterial signals in the water column versus the sediments. Proteobacteria and diatoms dominate the bacterial and eukaryote composition in the upper water column, while diatoms, dinoflagellates, and haptophytes notably decrease in relative abundance with increasing water depth. Little diatom sedaDNA is preserved in the sediments, which are instead dominated by Proteobacteria and Retaria. We compare the diatom microfossil and sedaDNA record and link the weak preservation of diatom sedaDNA to DNA degradation while sinking through the water column to the seafloor. This study provides the first assessment of DNA transfer from ocean waters to sediments and an overview of the microscopic communities occurring in the climatically important Totten Glacier region.
TREM2 deficiency in microglia accelerates photoreceptor cell death and immune cell infiltration following retinal detachment
Authors: Zhou Wenchuan , Zhou Yutong , He Jincan , Rao Yuqing , Fei Ping , Li Jing
Published: March 2023

Retinal detachment (RD) occurs in several major retinal conditions and often causes irreversible vision loss due to photoreceptor cell death. Retinal residential microglial cells are activated following RD and participate in photoreceptor cell death via direct phagocytosis and the regulation of inflammatory responses. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor exclusively expressed on microglial cells in the retina, and has been reported to affect microglial cell homeostasis, phagocytosis and inflammatory responses in the brain. In this study, increased expression of multiple cytokines and chemokines in the neural retina was observed starting at 3 h following RD. Trem2 knockout (Trem2−/−) mice exhibited significantly more photoreceptor cell death than wild-type controls at 3 days after RD, and the number of TUNEL positive photoreceptor cells progressively decreased from day 3 to day 7 post-RD. A significant thinning of the outer nuclear layer (ONL), with multiple folds was observed in the Trem2−/− mice at 3 days post-RD. Trem2 deficiency reduced microglial cell infiltration and phagocytosis of stressed photoreceptors. There were more neutrophils in Trem2−/− retina following RD than in controls. Using purified microglial cells, we found Trem2 knockout is associated with increased CXCL12 expression. The aggravated photoreceptor cell death was largely reversed by blocking the CXCL12-CXCR4 mediated chemotaxis in Trem2−/− mice after RD. Our findings suggested that retinal microglia are protective in preventing further photoreceptor cell death following RD by phagocytosing presumably stressed photoreceptor cells and by regulating inflammatory responses. TREM2 is largely responsible for such protective effect and CXCL12 plays an important role in regulating neutrophil infiltration after RD. Collectively, our study pinpointed TREM2 as a potential target of microglial cells to ameliorate RD-induced photoreceptor cell death.
Mitochondria-derived H2O2 triggers liver regeneration via FoxO3a signaling pathway after partial hepatectomy in mice
Authors: Bai Hua , Fang Cong-Wen , Shi Ying , Zhai Song , Jiang An , Li Ying-Na , Wang Lin , Liu Qi-Ling , Zhou Geng-Yao , Cao Jia-Hao , Li Jia , Yang Xue-Kang , Qin Xu-Jun
Published: March 2023

Reactive oxygen species (ROS) can induce oxidative injury and are generally regarded as toxic byproducts, although they are increasingly recognized for their signaling functions. Increased ROS often accompanies liver regeneration (LR) after liver injuries, however, their role in LR and the underlying mechanism remains unclear. Here, by employing a mouse LR model of partial hepatectomy (PHx), we found that PHx induced rapid increases of mitochondrial hydrogen peroxide (H2O2) and intracellular H2O2 at an early stage, using a mitochondria-specific probe. Scavenging mitochondrial H2O2 in mice with liver-specific overexpression of mitochondria-targeted catalase (mCAT) decreased intracellular H2O2 and compromised LR, while NADPH oxidases (NOXs) inhibition did not affect intracellular H2O2 or LR, indicating that mitochondria-derived H2O2 played an essential role in LR after PHx. Furthermore, pharmacological activation of FoxO3a impaired the H2O2-triggered LR, while liver-specific knockdown of FoxO3a by CRISPR-Cas9 technology almost abolished the inhibition of LR by overexpression of mCAT, demonstrating that FoxO3a signaling pathway mediated mitochondria-derived H2O2 triggered LR after PHx. Our findings uncover the beneficial roles of mitochondrial H2O2 and the redox-regulated underlying mechanisms during LR, which shed light on potential therapeutic interventions for LR-related liver injury. Importantly, these findings also indicate that improper antioxidative intervention might impair LR and delay the recovery of LR-related diseases in clinics.
Matrix Gla Protein drives stemness and tumor initiation in ovarian cancer
Authors: Nieddu V. , Melocchi V. , Battistini C. , Franciosa G. , Lupia M. , Stellato C. , Bertalot G. , Olsen J. V. , Colombo N. , Bianchi F. , Cavallaro U.
Published: March 2023

Ovarian cancer (OC) displays the highest mortality among gynecological tumors, mainly due to early peritoneal dissemination, the high frequency of tumor relapse following primary debulking, and the development of chemoresistance. All these events are thought to be initiated and sustained by a subpopulation of neoplastic cells, termed ovarian cancer stem cells (OCSC), that are endowed with self-renewing and tumor-initiating properties. This implies that interfering with OCSC function should offer novel therapeutic perspectives to defeat OC progression. To this aim, a better understanding of the molecular and functional makeup of OCSC in clinically relevant model systems is essential. We have profiled the transcriptome of OCSC vs. their bulk cell counterpart from a panel of patient-derived OC cell cultures. This revealed that Matrix Gla Protein (MGP), classically known as a calcification-preventing factor in cartilage and blood vessels, is markedly enriched in OCSC. Functional assays showed that MGP confers several stemness-associated traits to OC cells, including a transcriptional reprogramming. Patient-derived organotypic cultures pointed to the peritoneal microenvironment as a major inducer of MGP expression in OC cells. Furthermore, MGP was found to be necessary and sufficient for tumor initiation in OC mouse models, by shortening tumor latency and increasing dramatically the frequency of tumor-initiating cells. Mechanistically, MGP-driven OC stemness was mediated by the stimulation of Hedgehog signaling, in particular through the induction of the Hedgehog effector GLI1, thus highlighting a novel MGP/Hedgehog pathway axis in OCSC. Finally, MGP expression was found to correlate with poor prognosis in OC patients, and was increased in tumor tissue after chemotherapy, supporting the clinical relevance of our findings. Thus, MGP is a novel driver in OCSC pathophysiology, with a major role in stemness and in tumor initiation.
Caspase 6/NR4A1/SOX9 signaling axis regulates hepatic inflammation and pyroptosis in ischemia-stressed fatty liver
Authors: Sheng Mingwei , Weng Yiqi , Cao Yingli , Zhang Chen , Lin Yuanbang , Yu Wenli
Published: March 2023

The mechanism of nonalcoholic fatty liver susceptibility to ischemia/reperfusion (IR) injury has not been fully clarified. Caspase 6 is a critical regulator in innate immunity and host defense. We aimed to characterize the specific role of Caspase 6 in IR-induced inflammatory responses in fatty livers. Human fatty liver samples were harvested from patients undergoing ischemia-related hepatectomy to evaluate Caspase 6 expression. in mice model, we generated Caspase 6-knockout (Caspase 6KO) mice to investigate cellular and molecular mechanisms of macrophage Caspase 6 in IR-stimulated fatty livers. In human liver biopsies, Caspase 6 expression was upregulated combined with enhanced serum ALT level and severe histopathological injury in ischemic fatty livers. Moreover, Caspase 6 was mainly accumulated in macrophages but not hepatocytes. Unlike in controls, the Caspase 6-deficiency attenuated liver damage and inflammation activation. Activation of macrophage NR4A1 or SOX9 in Caspase 6-deficient livers aggravated liver inflammation. Mechanistically, macrophage NR4A1 co-localized with SOX9 in the nuclear under inflammatory conditions. Specifically, SOX9 acts as a coactivator of NR4A1 to directly target S100A9 transcription. Furthermore, macrophage S100A9 ablation dampened NEK7/NLRP3-driven inflammatory response and pyroptosis in macrophages. In conclusion, our findings identify a novel role of Caspase 6 in regulating NR4A1/SOX9 interaction in response to IR-stimulated fatty liver inflammation, and provide potential therapeutic targets for the prevention of fatty liver IR injury.
A holistic view on the role of egg yolk in Old Masters’ oil paints
Authors: Ranquet Ophélie , Duce Celia , Bramanti Emilia , Dietemann Patrick , Bonaduce Ilaria , Willenbacher Norbert
Published: March 2023

Old Masters like Botticelli used paints containing mixtures of oils and proteins, but “how” and “why” this was done is still not understood. Here, egg yolk is used in combination with two pigments to evaluate how different repartition of proteinaceous binder can be used to control the flow behavior as well as drying kinetics and chemistry of oil paints. Stiff paints enabling pronounced impasto can be achieved, but paint stiffening due to undesired uptake of humidity from the environment can also be suppressed, depending on proteinaceous binder distribution and colloidal paint microstructure. Brushability at high pigment loading is improved via reduction of high shear viscosity and wrinkling can be suppressed adjusting a high yield stress. Egg acts as antioxidant, slowing down the onset of curing, and promoting the formation of cross-linked networks less prone to oxidative degradation compared to oil alone, which might improve the preservation of invaluable artworks.
Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2
Authors: Sanders Brian C. , Pokhrel Suman , Labbe Audrey D. , Mathews Irimpan I. , Cooper Connor J. , Davidson Russell B. , Phillips Gwyndalyn , Weiss Kevin L. , Zhang Qiu , O’Neill Hugh , Kaur Manat , Schmidt Jurgen G. , Reichard Walter , Surendranathan Surekha , Parvathareddy Jyothi , Phillips Lexi , Rainville Christopher , Sterner David E. , Kumaran Desigan , Andi Babak , Babnigg Gyorgy , Moriarty Nigel W. , Adams Paul D. , Joachimiak Andrzej , Hurst Brett L. , Kumar Suresh , Butt Tauseef R. , Jonsson Colleen B. , Ferrins Lori , Wakatsuki Soichi , Galanie Stephanie , Head Martha S. , Parks Jerry M.
Published: March 2023

Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we design a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibits PLpro with kinact/KI = 9,600 M−1 s−1, achieves sub-μM EC50 values against three SARS-CoV-2 variants in mammalian cell lines, and does not inhibit a panel of human deubiquitinases (DUBs) at >30 μM concentrations of inhibitor. An X-ray co-crystal structure of the compound bound to PLpro validates our design strategy and establishes the molecular basis for covalent inhibition and selectivity against structurally similar human DUBs. These findings present an opportunity for further development of covalent PLpro inhibitors.
Arabidopsis TRB proteins function in H3K4me3 demethylation by recruiting JMJ14
Authors: Wang Ming , Zhong Zhenhui , Gallego-Bartolomé Javier , Feng Suhua , Shih Yuan-Hsin , Liu Mukun , Zhou Jessica , Richey John Curtis , Ng Charmaine , Jami-Alahmadi Yasaman , Wohlschlegel James , Wu Keqiang , Jacobsen Steven E.
Published: March 2023

Arabidopsis telomeric repeat binding factors (TRBs) can bind telomeric DNA sequences to protect telomeres from degradation. TRBs can also recruit Polycomb Repressive Complex 2 (PRC2) to deposit tri-methylation of H3 lysine 27 (H3K27me3) over certain target loci. Here, we demonstrate that TRBs also associate and colocalize with JUMONJI14 (JMJ14) and trigger H3K4me3 demethylation at some loci. The trb1/2/3 triple mutant and the jmj14-1 mutant show an increased level of H3K4me3 over TRB and JMJ14 binding sites, resulting in up-regulation of their target genes. Furthermore, tethering TRBs to the promoter region of genes with an artificial zinc finger (TRB-ZF) successfully triggers target gene silencing, as well as H3K27me3 deposition, and H3K4me3 removal. Interestingly, JMJ14 is predominantly recruited to ZF off-target sites with low levels of H3K4me3, which is accompanied with TRB-ZFs triggered H3K4me3 removal at these loci. These results suggest that TRB proteins coordinate PRC2 and JMJ14 activities to repress target genes via H3K27me3 deposition and H3K4me3 removal.
Identification of tagged glycans with a protein nanopore
Authors: Li Minmin , Xiong Yuting , Cao Yuchen , Zhang Chen , Li Yuting , Ning Hanwen , Liu Fan , Zhou Han , Li Xiaonong , Ye Xianlong , Pang Yue , Zhang Jiaming , Liang Xinmiao , Qing Guangyan
Published: March 2023

Structural complexity of glycans derived from the diversities in composition, linage, configuration, and branching considerably complicates structural analysis. Nanopore-based single-molecule sensing offers the potential to elucidate glycan structure and even sequence glycan. However, the small molecular size and low charge density of glycans have restricted direct nanopore detection of glycan. Here we show that glycan sensing can be achieved using a wild-type aerolysin nanopore by introducing a facile glycan derivatization strategy. The glycan molecule can induce impressive current blockages when moving through the nanopore after being connected with an aromatic group-containing tag (plus a carrier group for the neutral glycan). The obtained nanopore data permit the identification of glycan regio- and stereoisomers, glycans with variable monosaccharide numbers, and distinct branched glycans, either independently or with the use of machine learning methods. The presented nanopore sensing strategy for glycans paves the way towards nanopore glycan profiling and potentially sequencing.
The built-in electric field across FeN/Fe3N interface for efficient electrochemical reduction of CO2 to CO
Authors: Yin Jie , Jin Jing , Yin Zhouyang , Zhu Liu , Du Xin , Peng Yong , Xi Pinxian , Yan Chun-Hua , Sun Shouheng
Published: March 2023

Nanostructured metal-nitrides have attracted tremendous interest as a new generation of catalysts for electroreduction of CO2, but these structures have limited activity and stability in the reduction condition. Herein, we report a method of fabricating FeN/Fe3N nanoparticles with FeN/Fe3N interface exposed on the NP surface for efficient electrochemical CO2 reduction reaction (CO2RR). The FeN/Fe3N interface is populated with Fe−N4 and Fe−N2 coordination sites respectively that show the desired catalysis synergy to enhance the reduction of CO2 to CO. The CO Faraday efficiency reaches 98% at −0.4 V vs. reversible hydrogen electrode, and the FE stays stable from −0.4 to −0.9 V during the 100 h electrolysis time period. This FeN/Fe3N synergy arises from electron transfer from Fe3N to FeN and the preferred CO2 adsorption and reduction to *COOH on FeN. Our study demonstrates a reliable interface control strategy to improve catalytic efficiency of the Fe–N structure for CO2RR.
Epitaxially grown silicon-based single-atom catalyst for visible-light-driven syngas production
Authors: Chen Huai , Xiong Yangyang , Li Jun , Abed Jehad , Wang Da , Pedrazo-Tardajos Adrián , Cao Yueping , Zhang Yiting , Wang Ying , Shakouri Mohsen , Xiao Qunfeng , Hu Yongfeng , Bals Sara , Sargent Edward H. , Su Cheng-Yong , Yang Zhenyu
Published: March 2023

Improving the dispersion of active sites simultaneous with the efficient harvest of photons is a key priority for photocatalysis. Crystalline silicon is abundant on Earth and has a suitable bandgap. However, silicon-based photocatalysts combined with metal elements has proved challenging due to silicon’s rigid crystal structure and high formation energy. Here we report a solid-state chemistry that produces crystalline silicon with well-dispersed Co atoms. Isolated Co sites in silicon are obtained through the in-situ formation of CoSi2intermediate nanodomains that function as seeds, leading to the production of Co-incorporating silicon nanocrystals at the CoSi2/Si epitaxial interface. As a result, cobalt-on-silicon single-atom catalysts achieve an external quantum efficiency of 10% for CO2-to-syngas conversion, with CO and H2yields of 4.7 mol g(Co)−1and 4.4 mol g(Co)−1, respectively. Moreover, the H2/CO ratio is tunable between 0.8 and 2. This photocatalyst also achieves a corresponding turnover number of 2 × 104for visible-light-driven CO2reduction over 6 h, which is over ten times higher than previously reported single-atom photocatalysts.
In situ constructing atomic interface in ruthenium-based amorphous hybrid-structure towards solar hydrogen evolution
Authors: Liu Dong , Ding Tao , Wang Lifeng , Zhang Huijuan , Xu Li , Pang Beibei , Liu Xiaokang , Wang Huijuan , Wang Junhui , Wu Kaifeng , Yao Tao
Published: March 2023

The rational steering and construction of efficient and stable atomic interfaces is highly desirable but rather challenging in solar energy conversion. Here, we report an in-situ oxygen impregnation strategy to build abundant atomic interfaces composed of homogeneous Ru and RuOx amorphous hybrid-mixture with ultrafast charge transfer, for solar hydrogen evolution with sacrificial agent free. Via in-situ synchrotron X-ray absorption and photoelectron spectroscopies, we can precisely track and identify the gradual formation of atomic interfaces towards homogeneous Ru-RuOx hybrid-structure at the atomic level. Benefiting from the abundant interfaces, the amorphous RuOx sites can intrinsically trap the photoexcited hole within an ultrafast process (<100 fs), and the amorphous Ru sites enable subsequent electron transfer (~1.73 ps). Hence, this hybrid-structure triggers long-lived charge-separated states, and results in a high hydrogen evolution rate of 60.8 μmol·h−1. This design integrating the two sites fulfilled each half-reaction in a single hybrid-structure suggests potential guidelines towards efficient artificial photosynthesis.
Surpassing the repeaterless bound with a photon-number encoded measurement-device-independent quantum key distribution protocol
Authors: Erkılıç Özlem , Conlon Lorcán , Shajilal Biveen , Kish Sebastian , Tserkis Spyros , Kim Yong-Su , Lam Ping Koy , Assad Syed M.
Published: March 2023

Decoherence is detrimental to quantum key distribution (QKD) over large distances. One of the proposed solutions is to use quantum repeaters, which divide the total distance between the users into smaller segments to minimise the effects of the losses in the channel. Here we introduce a measurement-device-independent protocol which uses high-dimensional states prepared by two distant trusted parties and a coherent total photon number detection for the entanglement swapping measurement at the repeater station. We present an experimentally feasible protocol that can be implemented with current technology as the required states reduce down to the single-photon level over large distances. This protocol outperforms the existing measurement-device-independent and twin-field QKD protocols by achieving better key rates in general and higher transmission distance in total when experimental imperfections are considered. It also surpasses the fundamental limit of the repeaterless bound at a much shorter transmission distance in comparison to the existing TF-QKD protocols.