bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance and emission analysis of a CI engine fueled with parsley biodiesel–diesel blend
Authors: Bitire Sarah Oluwabunmi , Jen Tien-Chien
Published: July 2022

Pollution-induced environmental deterioration is one of the serious aspects that must be solved. As a result, biodiesel was made from a novel material (Parsley seed oil) through an alkali-induced transesterification reaction. The efficiency, as well as exhaust emission tests, were performed by running the prepared parsley biodiesel blends (mixture of biodiesel and diesel fuel in different proportions) in an engine. The ideal blend for enhancing engine performance was discovered to be B20, which displayed steady performance attributes without requiring any modifications to the diesel engine. The B20 parsley biodiesel blend had fewer emissions than diesel, notably hydrocarbons, and carbon monoxide except for nitrogen oxides and carbon dioxide. B20 Parsley blends were also shown to emit less pollution than other blends (B5 and B10). A high reduction in CO, CO2 and HC emissions for B20 was recorded at 33.9%, 29.73%, and 11.38% relative to diesel except for NOx. Brake-specific energy consumption decreases and thermal efficiency of the engine increases for all biodiesel blends. In addition, from the performance results, BTE and BSFC of B20 are relatively close to those of pure diesel fuel (B0). The use of parsley biodiesel as a diesel engine fuel was shown to be a promising strategy to promote the use of green fuels (biofuels from renewable materials) while simultaneously mitigating the release of toxic greenhouse gases from the combustion of fossil fuel.
Social Responsibility and Urban Consolidation Centres in Sustainable Freight Transport Markets
Authors: Crotti Daniele , Maggi Elena
Published: July 2022

This paper investigates the impact of Corporate Social Responsibility (CSR) strategies adopted by urban consolidation centres on the competition between logistics service providers. Taking into consideration pollution charges issued by city councils to reduce CO2 emissions in freight distribution, we study a Hotelling-like market setting where logistics providers could voluntarily outsource last mile deliveries to platforms endowed with eco-friendly vehicles. We considered the intensity of the competition, which is captured by switching costs and we theoretically find that in more contestable markets, the interplay between environmental policies and CSR strategies—intended as consumers-oriented pricing schemes—is more likely to enhance the demand by providers for consolidation centres’ deliveries. Conversely, when the competition is weak, i.e., the providers have a relatively strong market power, platforms’ services are less attractive and more relevant CSR pricing strategies are needed to spread out greener freight deliveries and make city logistics environmentally sustainable.
Multifunctional Flexible Humidity Sensor Systems Towards Noncontact Wearable Electronics
Authors: Lu Yuyao , Yang Geng , Shen Yajing , Yang Huayong , Xu Kaichen
Published: July 2022

In the past decade, the global industry and research attentions on intelligent skin-like electronics have boosted their applications in diverse fields including human healthcare, Internet of Things, human–machine interfaces, artificial intelligence and soft robotics. Among them, flexible humidity sensors play a vital role in noncontact measurements relying on the unique property of rapid response to humidity change. This work presents an overview of recent advances in flexible humidity sensors using various active functional materials for contactless monitoring. Four categories of humidity sensors are highlighted based on resistive, capacitive, impedance-type and voltage-type working mechanisms. Furthermore, typical strategies including chemical doping, structural design and Joule heating are introduced to enhance the performance of humidity sensors. Drawing on the noncontact perception capability, human/plant healthcare management, human–machine interactions as well as integrated humidity sensor-based feedback systems are presented. The burgeoning innovations in this research field will benefit human society, especially during the COVID-19 epidemic, where cross-infection should be averted and contactless sensation is highly desired.
Commercially Viable Hybrid Li-Ion/Metal Batteries with High Energy Density Realized by Symbiotic Anode and Prelithiated Cathode
Authors: Lin Kui , Xu Xiaofu , Qin Xianying , Liu Ming , Zhao Liang , Yang Zijin , Liu Qi , Ye Yonghuang , Chen Guohua , Kang Feiyu , Li Baohua
Published: July 2022

The energy density of commercial lithium (Li) ion batteries with graphite anode is reaching the limit. It is believed that directly utilizing Li metal as anode without a host could enhance the battery’s energy density to the maximum extent. However, the poor reversibility and infinite volume change of Li metal hinder the realistic implementation of Li metal in battery community. Herein, a commercially viable hybrid Li-ion/metal battery is realized by a coordinated strategy of symbiotic anode and prelithiated cathode. To be specific, a scalable template-removal method is developed to fabricate the porous graphite layer (PGL), which acts as a symbiotic host for Li ion intercalation and subsequent Li metal deposition due to the enhanced lithiophilicity and sufficient ion-conducting pathways. A continuous dissolution-deintercalation mechanism during delithiation process further ensures the elimination of dead Li. As a result, when the excess plating Li reaches 30%, the PGL could deliver an ultrahigh average Coulombic efficiency of 99.5% for 180 cycles with a capacity of 2.48 mAh cm−2 in traditional carbonate electrolyte. Meanwhile, an air-stable recrystallized lithium oxalate with high specific capacity (514.3 mAh g−1) and moderate operating potential (4.7–5.0 V) is introduced as a sacrificial cathode to compensate the initial loss and provide Li source for subsequent cycles. Based on the prelithiated cathode and initial Li-free symbiotic anode, under a practical-level 3 mAh capacity, the assembled hybrid Li-ion/metal full cell with a P/N ratio (capacity ratio of LiNi0.8Co0.1Mn0.1O2 to graphite) of 1.3 exhibits significantly improved capacity retention after 300 cycles, indicating its great potential for high-energy-density Li batteries.
Verification of sleep scales as predictors of suicidal ideation in Japanese dayworkers: a longitudinal study
Authors: Matsumoto Yuuki , Uchimura Naohisa , Ishitake Tatsuya , Itani Osamu , Otsuka Yuichiro
Published: July 2022

The objective of this study was to verify whether the assessment of poor sleep based on two sleep scales could predict suicidal ideation in Japanese dayworkers. A longitudinal survey was conducted among 446 Japanese dayworkers working at a company in Japan. Questionnaires were administered in 2013 (baseline) and 2014 (follow-up). To evaluate suicidal ideation, we used Question 19 of the Self-rating Depression Scale, categorizing participants who chose response options “some/a good part/most of the time” as suicidal ideation (+), and those who chose option “never or only a little of the time” as suicidal ideation (−). Two sleep scales, the Pittsburgh Sleep Quality Index (PSQI) and the 3-Dimensional Sleep Scale (3DSS), were selected as potential predictors of suicidal ideation. Only participants who were suicidal ideation (−) at baseline were included in the analysis, and suicidal ideation (+) individuals at follow-up were considered to have developed suicidal ideation during the interval between baseline and follow-up surveys. Data from 293 participants (236 men, 57 women) were analyzed. Twenty-two participants (7.5%) became suicidal ideation (+) at follow-up. Multiple logistic regression analysis showed that only sleep quality of the 3DSS subscale significantly predicted suicidal ideation, even after adjusting for depressive symptoms. That is, assessment of poor sleep did not predict suicidal ideation when based on the PSQI, but did when based on the 3DSS. Assessment of sleep quality based on the 3DSS may prove more useful in predicting worker suicidal ideation in industrial settings with limited facilities than PSQI.
Patient Confidentiality of Electronic Health Records: A Recent Review of the Saudi Literature
Authors: Almaghrabi Nada Saddig , Bugis Bussma Ahmed
Published: July 2022

Background

Health systems harbor lucrative data that can be targeted for illegal access, thus posing a serious privacy breach. In addition, patients could lose their lives or suffer permanent and irreversible harm due to such unauthorized access to health care data used in treatment. To ensure patient safety, the health care sector must integrate cybersecurity into its operations. Additionally, the health care industry must collaborate to tackle cybercrime and prevent unauthorized access to patient data. With the rapid transition from paper-based health records to electronic health records (EHRs), it is important to study, identify, and address the challenges that confront EHRs to protect patient confidentiality.

Aim

The main goal of this research was to create a clear picture of the role of EHRs in the health care system of Saudi Arabia regarding patient confidentiality. This work focused on the privacy and confidentiality challenges encountered in adopting EHRs in the health care system, and the advantages of using EHRs in terms of protecting patient confidentiality.

Methods

This project utilized a systematic literature review approach, and the methodology involved a careful critique of 11 recent articles.

Results

The confidentiality and privacy of patient data and information must be ensured, because the health care sector in Saudi Arabia is flawed with several security risks that may corrupt the integrity of patient data. The health care system is facing many cybercrimes whereby hackers can gain access to confidential data and patient information. Internal factors such as inexperienced medical personnel have also necessitated EHRs in Saudi Arabia. Health care workers who lack the appropriate skills in handling EHRs may cause breaches of patient data, which in turn may compromise the health and safety of the patients.

Conclusion

Confidentiality and privacy are critical components of a reliable EHR system. EHR confidentiality has a significant impact on maintaining patient safety and security, thus enhancing patient care in Saudi Arabia. Additionally, challenges such as hackers and data breaches have slowed the adoption process among health care companies in Saudi Arabia.
Dynamic Capabilities
Authors: Nooteboom Bart
Published: July 2022

The development of salient ideas and publications on dynamic capabilities is given, extended by ideas outside the literature of strategic management. Dynamic capability is presented as an interdisciplinary subject to which knowledge is central. Diversity of knowledge is treated in terms of cognitive distance, limited through organisational focus. To deal with diversity, development and uncertainty, evolutionary theory and the notion of entropy are used. The relation between individual and organisational knowledge is modelled with the notion of a script and linguistic ideas. The governance of collaborative relations for innovation is discussed, including trust, which are also dynamic capabilities.
Human Rights and Social Work
Authors: Ife Jim , Soldatić Karen , Briskman Linda
Published: July 2022

Human Rights and Social Work: Towards Rights-Based Practice helps students and practitioners understand how human rights concepts underpin the social work profession and inform their practice. This book examines the three generations of human rights and the systems of oppression that prevent citizens from participating in society as equals. It explores a range of topics, from ethics and ethical social work practice, to deductive and inductive approaches to human rights, and global and local human rights discourses. The language, processes, structures and theories of social work that are fundamental to the profession are also discussed. This edition features case studies exploring current events, movements and human rights crises, including the Black Lives Matter movement, the Northern Territory Emergency Response, and homelessness among LGBTIQA+ young people. This edition is accompanied by online resources for both students and instructors. Human Rights and Social Work is an indispensable guide for social work students and practitioners.
Predictability effects in degraded speech comprehension are reduced as a function of attention
Authors: Bhandari Pratik , Demberg Vera , Kray Jutta
Published: July 2022

The aim of this study was to examine the role of attention in understanding linguistic information even in a noisy environment. To assess the role of attention, we varied task instructions in two experiments in which participants were instructed to listen to short sentences and thereafter to type in the last word they heard or to type in the whole sentence. We were interested in how these task instructions influence the interplay between top-down prediction and bottom-up perceptual processes during language comprehension. Therefore, we created sentences that varied in the degree of predictability (low, medium, and high) as well as in the degree of speech degradation (four, six, and eight noise-vocoding channels). Results indicated better word recognition for highly predictable sentences for moderate, though not for high, levels of speech degradation, but only when attention was directed to the whole sentence. This underlines the important role of attention in language comprehension.
Why, When, and How did Nationalism Become Grounded?
Authors: Mylonas Harris
Published: July 2022

Siniša Malešević’s Grounded Nationalisms asks: “Why has nationalism proved to be such a potent, protean, and durable force in the modern age? Why has the nation-state established itself as the central organizing mode of social and political life in the last two hundred years? Why is nationalism still the dominant form of collective subjectivity?” (8) The author draws from several disciplines to tackle these questions, including sociology, political science, history, psychology, demography, and anthropology. In a nutshell, he finds the answer rests in the historical origins and organizational, ideological, and micro-interactional dynamics of nationalist ideologies that evolve and adapt over time. This book is an instant classic of historical sociology arguing that nationalism is the dominant form of modern subjectivity and unlikely to be replaced or shaken by globalization or neoliberalism.
Surfaces of prescribed linear Weingarten curvature in
Authors: Bueno Antonio , Ortiz Irene
Published: July 2022

Given $a,\,b\in \mathbb {R}$ and $\Phi \in C^{1}(\mathbb {S}^{2})$, we study immersed oriented surfaces $\Sigma$ in the Euclidean 3-space $\mathbb {R}^{3}$ whose mean curvature $H$ and Gauss curvature $K$ satisfy $2aH+bK=\Phi (N)$, where $N:\Sigma \rightarrow \mathbb {S}^{2}$ is the Gauss map. This theory widely generalizes some of paramount importance such as the ones constant mean and Gauss curvature surfaces, linear Weingarten surfaces and self-translating solitons of the mean curvature flow. Under mild assumptions on the prescribed function $\Phi$, we exhibit a classification result for rotational surfaces in the case that the underlying fully nonlinear PDE that governs these surfaces is elliptic or hyperbolic.
Successful use of ivabradine in a 10-year-old patient with graft failure after heart transplantation
Authors: Ogawa Yosuke , Urata Susumu , Inuzuka Ryo
Published: July 2022

We encountered a paediatric case of graft failure due to antibody-mediated rejection after heart transplantation in which ivabradine was effective. Inappropriate sinus tachycardia in denervated transplanted hearts is a good indication for ivabradine administration as beta-blockers have a limited efficacy. To our knowledge, this is the first report on the effectiveness of ivabradine in a paediatric heart transplant rejection case.
Automated Quantitative Mapping of Ore Minerals by Multispectral Reflected-light Microscopy
Authors: Catalina Juan Carlos , Grunwald Úrsula , Alarcón David , Castroviejo Ricardo
Published: July 2022

An innovative multispectral reflected-light microscopy system is able to automatically identify ore minerals by measuring their specular reflectance with non-polarized light in a number of spectral bands, and comparing the values obtained with a reference database. In this way it can provide quantitative mineralogical mapping comparable to that obtained from automated mineralogy systems based on SEM-EDS (Scanning Electron Microscopy with Energy-Dispersive X-Ray Spectroscopy), at a fraction of the cost and with less stringent environmental and operational requirements.

The new system, called AMCO (for Automated Microscopic Characterization of Ores), consists of an instrument and two proprietary software applications: amcoCapture, to acquire multispectral images of a polished section prepared from an ore sample, and amcoAnalysis, to process these images and extract different types of mineralogical information from them.
Radiographers’ perception on the provision of psychosocial support for cancer patients
Authors: Azzopardi Jade , Mercieca Susan , Portelli Jonathan Loui
Published: July 2022

Introduction:

Therapeutic radiographers are the first point of contact for cancer patients undergoing radiotherapy treatment and therefore have an important role in providing both physical and psychosocial support to these patients. This study aimed to evaluate therapeutic radiographers’ perception about their role in identifying and providing psychosocial support for patients receiving RT treatment.

Method:

The study used a cross-sectional, prospective research design. A self-designed questionnaire was distributed to all therapeutic radiographers (n = 26) working at a radiotherapy department in Malta.

Results:

A total of 21 therapeutic radiographers completed the questionnaire. All participants felt that the provision of psychological care was an important part of their role as therapeutic radiographers. The majority of the participants reported having the most confidence in giving treatment-related symptoms advice rather than psychological support. The most common barrier to providing psychological support was lack of training (95·2%), followed by the lack of an appropriate screening tool (85·7%), availability of private space to talk to patients (76·2%) and a lack of knowledge (61·9%).

Conclusion:

While most therapeutic radiographers believed that providing psychosocial support was an important aspect of their role, several barriers prevented them from fulfilling this role. Training, the introduction of a psychosocial screening tool and clear referral processes are recommended to improve radiotherapy service.
Priority setting and cross-country learning: the relevance of TO-REACH for primary care
Authors: Groenewegen Peter , Hansen Johan , Fahy Nick , Haarmann Alexander , Montante Sabrina , Azzopardi Muscat Natasha , Poldrugovac Mircha , Ricciardi Walter , Tomaselli Gianpaolo
Published: July 2022

Aim:

To inform the primary care community about priorities for research in primary care as came up from the European project TO-REACH and to discuss transferability of service and policy innovations between countries.

Background:

TO-REACH stands for Transfer of Organizational innovations for Resilient, Effective, equitable, Accessible, sustainable and Comprehensive Health services and systems. This EU-funded project has put health systems and services research higher on the European agenda and has led to the current development of a European ‘Partnership Transforming Health and Care Systems’.

Methods:

To identify research priorities, both qualitative and quantitative approaches were used. Policy documents and strategic roadmaps were searched, and priorities were mapped. Stakeholders were involved through national roundtable consultations and online consultations. Regarding transferability, we carried out a review of the literature, guided by a conceptual framework, and using a snowballing approach.

Findings:

Primary care emerged as an important priority from the inventory, as are areas that are conducive to strengthening primary care, such as workforce policies. The large variation in service organisation and policy around primary care in Europe is a huge potential for cross-country learning. However, the simple transfer of primary care service and policy arrangements from one health system to another has a big chance to fail, unless known conditions for successful transfer are taken into account and gaps in our knowledge about transfer are resolved.
Knowledge, attitudes, and practices regarding vaccination among community pharmacists
Authors: Ozdemir Nesligul , Kara Emre , Bayraktar-Ekincioglu Aygin , Buyukcam Ayse , Celiker Ayce , Demirkan Kutay , Kara Ates
Published: July 2022

Background:

Healthcare professionals’ vaccine recommendation is the most effective method to increase vaccination rates of the community. The vaccine counseling and recommendation behavior of pharmacists, who are among the easily accessible healthcare professionals, are influenced by their knowledge and attitudes about vaccines.

Aim:

It was aimed to investigate community pharmacists’ knowledge, attitudes, and practices regarding commonly used vaccines.

Methods:

A cross-sectional study was conducted as an online survey with a sample of 1100 community pharmacists in Turkey. Pharmacists were invited to participate in the study by phone calls. A structured survey, which consists of 40 questions to assess the knowledge, attitudes, and practices regarding vaccines, was sent to the e-mail addresses of pharmacists who volunteered to participate in the study.

Findings:

A total of 430 pharmacists completed the survey. Thirty percent of pharmacists had lack of knowledge about vaccination during pregnancy, whereas 52.2% and 31.4% of pharmacists believed that tetanus and influenza vaccines should be provided during pregnancy, respectively. Nearly 89% of pharmacists recommended vaccines to patients, mainly for influenza vaccine (83.9%). Only 31.5% of pharmacists had been vaccinated against influenza in the last season, whereas 50.5% had never been vaccinated. Pharmacists who had been vaccinated with influenza vaccine had a high rate of recommending influenza vaccines to the patients.

Conclusion:

The present study found that vaccination among pharmacists in Turkey and their knowledge on vaccination during pregnancy were low. Further education of pharmacists to improve their knowledge and attitudes toward vaccines is needed.
Shifting into Digital Services: Does a Financial Crisis Matter and for Who?
Authors: van der Marel Erik
Published: July 2022

Did trade patterns in services change into activities that were more digital-intense after the Global Financial Crisis (GFC) of 2008, and was this shift structural? This paper uses a Difference-in-Difference (DID) approach to investigate whether services trade became more digital-based after the GFC in 2008. It finds support that the GFC formed a break from the previous period that caused services trade to become more digital – although there are signs that this had already started before 2008. Countries with high internet usage and a comparative advantage in digital-intense services, such as R&D, information exchange, computer services, and charges for Intellectual Property Rights (IPR), on average saw post-GFC a 6% increase in global exports compared to other non-digital sectors. More striking is that upper-middle income countries and countries with medium levels of skills also witnessed a sharp increase. These significant outcomes may indicate the direction into which patterns of services trade are likely to turn after the current economic crisis resulting from COVID-19.
Earth’s Wobbly Inner Core Illuminated by Nuclear Explosions
Authors: Schmidt Jennifer
Published: July 2022

Shock waves from Cold War era nuclear tests gave seismologists a glimpse of the inner core. Its wobbly rotation could explain phenomena such as the periodic change in the length of a day.
Creating the perfect plasmonic wave
Authors: Steinmeyer Günter
Published: July 2022

Exploiting a plasmonic resonance, near-perfect grating structures have been reported, with a regularity that exceeds typical commercially available diffraction gratings.
MYT1L in the making: emerging insights on functions of a neurodevelopmental disorder gene
Authors: Chen Jiayang , Yen Allen , Florian Colin P. , Dougherty Joseph D.
Published: July 2022

Large scale human genetic studies have shown that loss of function (LoF) mutations in MYT1L are implicated in neurodevelopmental disorders (NDDs). Here, we provide an overview of the growing number of published MYT1L patient cases, and summarize prior studies in cells, zebrafish, and mice, both to understand MYT1L’s molecular and cellular role during brain development and consider how its dysfunction can lead to NDDs. We integrate the conclusions from these studies and highlight conflicting findings to reassess the current model of the role of MYT1L as a transcriptional activator and/or repressor based on the biological context. Finally, we highlight additional functional studies that are needed to understand the molecular mechanisms underlying pathophysiology and propose key questions to guide future preclinical studies.
Matrix transfer techniques for direct paste composite resins
Authors: Bailey Oliver , McGuirk Colin , O´Connor Christopher
Published: July 2022

This article discusses potential concerns and important considerations when selecting and using matrix transfer techniques for the direct, definitive addition of composite resin to teeth. It also provides guidance to aid these processes with the use of case studies, primarily focusing on the management of tooth wear.
Mitotic SENP3 activation couples with cGAS signaling in tumor cells to stimulate anti-tumor immunity
Authors: Hu Gaolei , Chen Yalan , Yang Xinyu , Wang Yang , He Jianli , Wang Tianshi , Fan Qiuju , Deng Liufu , Tu Jun , Tan Hongsheng , Cheng Jinke
Published: July 2022

Our previous studies show that the mitotic phosphorylation of SUMO-specific protease 3 (SENP3) can inhibit its de-SUMOylation activity in G2/M phase of the cell cycle. Inhibition of SENP3 plays a critical role in the correct separation of sister chromatids in mitosis. The mutation of mitotic SENP3 phosphorylation causes chromosome instability and promotes tumorigenesis. In this study, we find that the mutation of mitotic SENP3 phosphorylation in tumor cells can suppress tumor growth in immune-competent mouse model. We further detect an increase of CD8+ T cell infiltration in the tumors, which is essential for the anti-tumor effect in immune-competent mouse model. Moreover, we find that mitotic SENP3 activation increases micronuclei formation, which can activate cGAS signaling-dependent innate immune response. We confirmed that cGAS signaling mediates the mitotic SENP3 activation-induced anti-tumor immunity. We further show that p53 responding to DNA damage activates mitotic SENP3 by inhibiting phosphorylation, and further increases cellular senescence as well as the related innate immune response in tumor cells. Furthermore, TCGA database demonstrates that the SENP3 expression positively correlates with the induction of innate immune response as well as the survival of the p53 mutant pancreatic cancer patients. Together, these data reveal that mitotic SENP3 activation in tumor cells can promote host anti-tumor immune response by coupling with cGAS signaling.
Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections
Authors: Zhang Guangzhi , Wang Jinyong , Zhao Zhanran , Xin Ting , Fan Xuezheng , Shen Qingchun , Raheem Abdul , Lee Chae Rhim , Jiang Hui , Ding Jiabo
Published: July 2022

Since the discovery of cell apoptosis, other gene-regulated cell deaths are gradually appreciated, including pyroptosis, ferroptosis, and necroptosis. Necroptosis is, so far, one of the best-characterized regulated necrosis. In response to diverse stimuli (death receptor or toll-like receptor stimulation, pathogenic infection, or other factors), necroptosis is initiated and precisely regulated by the receptor-interacting protein kinase 3 (RIPK3) with the involvement of its partners (RIPK1, TRIF, DAI, or others), ultimately leading to the activation of its downstream substrate, mixed lineage kinase domain-like (MLKL). Necroptosis plays a significant role in the host’s defense against pathogenic infections. Although much has been recognized regarding modulatory mechanisms of necroptosis during pathogenic infection, the exact role of necroptosis at different stages of infectious diseases is still being unveiled, e.g., how and when pathogens utilize or evade necroptosis to facilitate their invasion and how hosts manipulate necroptosis to counteract these detrimental effects brought by pathogenic infections and further eliminate the encroaching pathogens. In this review, we summarize and discuss the recent progress in the role of necroptosis during a series of viral, bacterial, and parasitic infections with zoonotic potentials, aiming to provide references and directions for the prevention and control of infectious diseases of both human and animals.
Accumulation of oncometabolite D-2-Hydroxyglutarate by SLC25A1 inhibition: A metabolic strategy for induction of HR-ness and radiosensitivity
Authors: Xiang Kexu , Kalthoff Christian , Münch Corinna , Jendrossek Verena , Matschke Johann
Published: July 2022

Oncogenic mutations in metabolic genes and associated oncometabolite accumulation support cancer progression but can also restrict cellular functions needed to cope with DNA damage. For example, gain-of-function mutations in isocitrate dehydrogenase (IDH) and the resulting accumulation of the oncometabolite D-2-hydroxyglutarate (D-2-HG) enhanced the sensitivity of cancer cells to inhibition of poly(ADP-ribose)-polymerase (PARP)1 and radiotherapy (RT). In our hand, inhibition of the mitochondrial citrate transport protein (SLC25A1) enhanced radiosensitivity of cancer cells and this was associated with increased levels of D-2-HG and a delayed repair of radiation-induced DNA damage. Here we aimed to explore the suggested contribution of D-2-HG-accumulation to disturbance of DNA repair, presumably homologous recombination (HR) repair, and enhanced radiosensitivity of cancer cells with impaired SLC25A1 function. Genetic and pharmacologic inhibition of SLC25A1 (SLC25A1i) increased D-2-HG-levels and sensitized lung cancer and glioblastoma cells to the cytotoxic action of ionizing radiation (IR). SLC25A1i-mediated radiosensitization was abrogated in MEFs with a HR-defect. D-2-HG-accumulation was associated with increased DNA damage and delayed resolution of IR-induced γH2AX and Rad51 foci. Combining SLC25A1i with PARP- or the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs)-inhibitors further potentiated IR-induced DNA damage, delayed DNA repair kinetics resulting in radiosensitization of cancer cells. Importantly, proof of concept experiments revealed that combining SLC25A1i with IR without and with PARPi also reduced tumor growth in the chorioallantoic membrane (CAM) model in vivo. Thereby SLC25A1i offers an innovative strategy for metabolic induction of context-dependent lethality approaches in combination with RT and clinically relevant inhibitors of complementary DNA repair pathways.
RBCK1 promotes hepatocellular carcinoma metastasis and growth by stabilizing RNF31
Authors: Chen Xijun , Ye Qing , Zhao Wenxiu , Chi Xiaoqin , Xie Chengrong , Wang Xiaomin
Published: July 2022

RNF31 (HOIP), RBCK1 (HOIL-1L), and SHARPIN are subunits of the linear ubiquitin chain assembly complex. Their function and specific molecular mechanisms in hepatocellular carcinoma (HCC) have not been reported previously. Here, we investigated the role of RNF31 and RBCK1 in HCC. We showed that RNF31 and RBCK1 were overexpressed in HCC and that upregulation of RNF31 and RBCK1 indicated poor clinical outcomes in patients with HCC. RNF31 overexpression was significantly associated with more satellite foci and vascular invasion in patients with HCC. Additionally, RBCK1 expression correlated positively with RNF31 expression in HCC tissues. Functionally, RBCK1 and RNF31 promote the metastasis and growth of HCC cells. Moreover, the RNF31 inhibitor gliotoxin inhibited the malignant behavior of HCC cells. Mechanistically, RBCK1 interacted with RNF31 and repressed its ubiquitination and proteasomal degradation. In summary, the present study revealed an oncogenic role and regulatory relationship between RBCK1 and RNF31 in facilitating proliferation and metastasis in HCC, suggesting that they are potential prognostic markers and therapeutic targets for HCC.
Development of plasmonic thin-layer chromatography for size-selective and optical-property-dependent separation of quantum dots
Authors: Torimoto Tsukasa , Yamaguchi Naoko , Maeda Yui , Akiyoshi Kazutaka , Kameyama Tatsuya , Nagai Tatsuya , Shoji Tatsuya , Yamane Hidemasa , Ishihara Hajime , Tsuboi Yasuyuki
Published: July 2022

Nano-objects, such as quantum dots (QDs), are essential units for the construction of functional materials and devices in current technologies. The establishment of a versatile scheme to sort desired components from a crude product is crucial for bringing out the full potential of the original materials. However, it is still challenging to separate QDs with the same composition on the basis of size and to sort QDs with the same size but different optical properties. Here, we demonstrate such sorting for the first time by combining plasmonic optical trapping with thin-layer chromatography (TLC), which is a widely used tool. LED photoexcitation of the localized surface plasmon resonance of Au nanoparticles immobilized on a TLC plate affected the distance QDs traveled depending on the wavelength and intensity of irradiated light, which led to clear separation according to the size and/or optical properties of the QDs. Since optical property-based separation cannot be achieved by conventional chromatography, in which the interactions between stationary phases of chromatographs and QDs are simply based on differences in the size or surface functionality of the QDs, the present strategy will be a key solution for the establishment of a versatile scheme for sorting nano-objects.
A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells
Authors: Ye Yingying , Barghouth Mohammad , Dou Haiqiang , Luan Cheng , Wang Yongzhi , Karagiannopoulos Alexandros , Jiang Xiaoping , Krus Ulrika , Fex Malin , Zhang Quan , Eliasson Lena , Rorsman Patrik , Zhang Enming , Renström Erik
Published: July 2022

Glucose-induced insulin secretion depends on β-cell electrical activity. Inhibition of ATP-regulated potassium (KATP) channels is a key event in this process. However, KATP channel closure alone is not sufficient to induce β-cell electrical activity; activation of a depolarizing membrane current is also required. Here we examine the role of the mechanosensor ion channel PIEZO1 in this process. Yoda1, a specific PIEZO1 agonist, activates a small membrane current and thereby triggers β-cell electrical activity with resultant stimulation of Ca2+-influx and insulin secretion. Conversely, the PIEZO1 antagonist GsMTx4 reduces glucose-induced Ca2+-signaling, electrical activity and insulin secretion. Yet, PIEZO1 expression is elevated in islets from human donors with type-2 diabetes (T2D) and a rodent T2D model (db/db mouse), in which insulin secretion is reduced. This paradox is resolved by our finding that PIEZO1 translocates from the plasmalemma into the nucleus (where it cannot influence the membrane potential of the β-cell) under experimental conditions emulating T2D (high glucose culture). β-cell-specific Piezo1-knockout mice show impaired glucose tolerance in vivo and reduced glucose-induced insulin secretion, β-cell electrical activity and Ca2+ elevation in vitro. These results implicate mechanotransduction and activation of PIEZO1, via intracellular accumulation of glucose metabolites, as an important physiological regulator of insulin secretion.
Probing the mesoscopic size limit of quantum anomalous Hall insulators
Authors: Deng Peng , Eckberg Christopher , Zhang Peng , Qiu Gang , Emmanouilidou Eve , Yin Gen , Chong Su Kong , Tai Lixuan , Ni Ni , Wang Kang L.
Published: July 2022

The inelastic scattering length (Ls) is a length scale of fundamental importance in condensed matters due to the relationship between inelastic scattering and quantum dephasing. In quantum anomalous Hall (QAH) materials, the mesoscopic length scale Ls plays an instrumental role in determining transport properties. Here we examine Ls in three regimes of the QAH system with distinct transport behaviors: the QAH, quantum critical, and insulating regimes. Although the resistance changes by five orders of magnitude when tuning between these distinct electronic phases, scaling analyses indicate a universal Ls among all regimes. Finally, mesoscopic scaled devices with sizes on the order of Ls were fabricated, enabling the direct detection of the value of Ls in QAH samples. Our results unveil the fundamental length scale that governs the transport behavior of QAH materials.
Intratumor graph neural network recovers hidden prognostic value of multi-biomarker spatial heterogeneity
Authors: Qiu Lida , Kang Deyong , Wang Chuan , Guo Wenhui , Fu Fangmeng , Wu Qingxiang , Xi Gangqin , He Jiajia , Zheng Liqin , Zhang Qingyuan , Liao Xiaoxia , Li Lianhuang , Chen Jianxin , Tu Haohua
Published: July 2022

Biomarkers are indispensable for precision medicine. However, focused single-biomarker development using human tissue has been complicated by sample spatial heterogeneity. To address this challenge, we tested a representation of primary tumor that synergistically integrated multiple in situ biomarkers of extracellular matrix from multiple sampling regions into an intratumor graph neural network. Surprisingly, the differential prognostic value of this computational model over its conventional non-graph counterpart approximated that of combined routine prognostic biomarkers (tumor size, nodal status, histologic grade, molecular subtype, etc.) for 995 breast cancer patients under a retrospective study. This large prognostic value, originated from implicit but interpretable regional interactions among the graphically integrated in situ biomarkers, would otherwise be lost if they were separately developed into single conventional (spatially homogenized) biomarkers. Our study demonstrates an alternative route to cancer prognosis by taping the regional interactions among existing biomarkers rather than developing novel biomarkers.
TDP1-independent pathways in the process and repair of TOP1-induced DNA damage
Authors: Zhang Huimin , Xiong Yun , Su Dan , Wang Chao , Srivastava Mrinal , Tang Mengfan , Feng Xu , Huang Min , Chen Zhen , Chen Junjie
Published: July 2022

Anticancer drugs, such as camptothecin (CPT), trap topoisomerase I (TOP1) on DNA and form TOP1 cleavage complexes (TOP1cc). Alternative repair pathways have been suggested in the repair of TOP1cc. However, how these pathways work with TDP1, a key repair enzyme that specifically hydrolyze the covalent bond between TOP1 catalytic tyrosine and the 3’-end of DNA and contribute to the repair of TOP1cc is poorly understood. Here, using unbiased whole-genome CRISPR screens and generation of co-deficient cells with TDP1 and other genes, we demonstrate that MUS81 is an important factor that mediates the generation of excess double-strand breaks (DSBs) in TDP1 KO cells. APEX1/2 are synthetic lethal with TDP1. However, deficiency of APEX1/2 does not reduce DSB formation in TDP1 KO cells. Together, our data suggest that TOP1cc can be either resolved directly by TDP1 or be converted into DSBs and repaired further by the Homologous Recombination (HR) pathway.
Development of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis
Authors: Wang Zhengan , Gu Chao , Sun Lu , Zhao Feng , Fu Ying , Di Lingfang , Zhang Junxiong , Zhuang Hemu , Jiang Shengnan , Wang Haiping , Zhu Feiteng , Chen Yiyi , Chen Mengzhen , Ling Xia , Chen Yan , Yu Yunsong
Published: July 2022

Staphylococcus capitis, which causes bloodstream infections in neonatal intensive care units, is a common cause of healthcare-associated infections. Thus, a standardized high-resolution typing method to document the transmission and dissemination of multidrug-resistantS. capitisisolates is required. We aimed to establish a core genome multilocus sequence typing (cgMLST) scheme to surveilS. capitis. The cgMLST scheme was defined based on primary and validation genome sets and tested with outbreaks of linezolid-resistant isolates and a validation set. Phylogenetic analysis was performed to investigate the population structure and compare it with the result of cgMLST analysis. TheS. capitispopulation consists of 1 dominant, NRCS-A, and 4 less common clones. In this work, a multidrug-resistant clone (L clone) with linezolid resistance is identified. With the features of type III SCCmecand multiple copies of mutations of G2576T and C2104T in the 23S rRNA, the L clone has been spreading silently across China.
Forecasting the evolution of fast-changing transportation networks using machine learning
Authors: Lei Weihua , Alves Luiz G. A. , Amaral Luís A. Nunes
Published: July 2022

Transportation networks play a critical role in human mobility and the exchange of goods, but they are also the primary vehicles for the worldwide spread of infections, and account for a significant fraction of CO2 emissions. We investigate the edge removal dynamics of two mature but fast-changing transportation networks: the Brazilian domestic bus transportation network and the U.S. domestic air transportation network. We use machine learning approaches to predict edge removal on a monthly time scale and find that models trained on data for a given month predict edge removals for the same month with high accuracy. For the air transportation network, we also find that models trained for a given month are still accurate for other months even in the presence of external shocks. We take advantage of this approach to forecast the impact of a hypothetical dramatic reduction in the scale of the U.S. air transportation network as a result of policies to reduce CO2 emissions. Our forecasting approach could be helpful in building scenarios for planning future infrastructure.
A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer
Authors: Kelly Michael R. , Wisniewska Kamila , Regner Matthew J. , Lewis Michael W. , Perreault Andrea A. , Davis Eric S. , Phanstiel Douglas H. , Parker Joel S. , Franco Hector L.
Published: July 2022

The human genome contains regulatory elements, such as enhancers, that are often rewired by cancer cells for the activation of genes that promote tumorigenesis and resistance to therapy. This is especially true for cancers that have little or no known driver mutations within protein coding genes, such as ovarian cancer. Herein, we utilize an integrated set of genomic and epigenomic datasets to identify clinically relevant super-enhancers that are preferentially amplified in ovarian cancer patients. We systematically probe the top 86 super-enhancers, using CRISPR-interference and CRISPR-deletion assays coupled to RNA-sequencing, to nominate two salient super-enhancers that drive proliferation and migration of cancer cells. Utilizing Hi-C, we construct chromatin interaction maps that enable the annotation of direct target genes for these super-enhancers and confirm their activity specifically within the cancer cell compartment of human tumors using single-cell genomics data. Together, our multi-omic approach examines a number of fundamental questions about how regulatory information encoded into super-enhancers drives gene expression networks that underlie the biology of ovarian cancer.
Structure of DNMT3B homo-oligomer reveals vulnerability to impairment by ICF mutations
Authors: Gao Linfeng , Guo Yiran , Biswal Mahamaya , Lu Jiuwei , Yin Jiekai , Fang Jian , Chen Xinyi , Shao Zengyu , Huang Mengjiang , Wang Yinsheng , Wang Gang Greg , Song Jikui
Published: July 2022

DNA methyltransferase DNMT3B plays an essential role in establishment of DNA methylation during embryogenesis. Mutations of DNMT3B are associated with human diseases, notably the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. How ICF mutations affect DNMT3B activity is not fully understood. Here we report the homo-oligomeric structure of DNMT3B methyltransferase domain, providing insight into DNMT3B-mediated DNA methylation in embryonic stem cells where the functional regulator DNMT3L is dispensable. The interplay between one of the oligomer interfaces (FF interface) and the catalytic loop renders DNMT3B homo-oligomer a conformation and activity distinct from the DNMT3B-DNMT3L heterotetramer, and a greater vulnerability to certain ICF mutations. Biochemical and cellular analyses further reveal that the ICF mutations of FF interface impair the DNA binding and heterochromatin targeting of DNMT3B, leading to reduced DNA methylation in cells. Together, this study provides a mechanistic understanding of DNMT3B-mediated DNA methylation and its dysregulation in disease.
Ultrastrong and multifunctional aerogels with hyperconnective network of composite polymeric nanofibers
Authors: He Huimin , Wei Xi , Yang Bin , Liu Hongzhen , Sun Mingze , Li Yanran , Yan Aixin , Tang Chuyang Y. , Lin Yuan , Xu Lizhi
Published: July 2022

Three-dimensional (3D) microfibrillar network represents an important structural design for various natural tissues and synthetic aerogels. Despite extensive efforts, achieving high mechanical properties for synthetic 3D microfibrillar networks remains challenging. Here, we report ultrastrong polymeric aerogels involving self-assembled 3D networks of aramid nanofiber composites. The interactions between the nanoscale constituents lead to assembled networks with high nodal connectivity and strong crosslinking between fibrils. As revealed by theoretical simulations of 3D networks, these features at fibrillar joints may lead to an enhancement of macroscopic mechanical properties by orders of magnitude even with a constant level of solid content. Indeed, the polymeric aerogels achieved both high specific tensile modulus of ~625.3 MPa cm3 g−1 and fracture energy of ~4700 J m−2, which are advantageous for diverse structural applications. Furthermore, their simple processing techniques allow fabrication into various functional devices, such as wearable electronics, thermal stealth, and filtration membranes. The mechanistic insights and manufacturability provided by these robust microfibrillar aerogels may create further opportunities for materials design and technological innovation.