bluuebunny/crossref_metadata_2025 huggingface dataset:
Enacting the babushka: older Russian women ‘doing’ age, gender and class by accepting the role of a stoic carer
Authors: Shadrina Anna
Published: April 2022

This article contributes to the debates about age-based practices of distinction that produce stable notions about the subjectivities of members of social categories and the social consequences of such categorisations for the subject. In Russia, a strong expectation that grandmothers will prioritise helping their adult daughters with child care and housework over their careers and personal lives shaped the social position of the babushka, an unpaid family carer dependent on the state and her children. When women can no longer maintain meaningful post-pension-age employment, they see the babushka figure as the dominant option on which to model their identities. Drawing on 20 biographical interviews with women aged 60 and over, the article explores their tactics of performing their ‘gendered age’ in various classed ways. The babushka identity encompasses two broad strategies of self-presentation: taking control over one's life by emphasising that it is one's deliberate choice to live as a post-professional and post-sexual subject, and downplaying one's own needs while contributing to the wellbeing of others. The article shows that for older Russian women who face sexism, ageism and the stigmatisation of poverty, denying their vulnerability to systemic marginalisation is a familiar way of seeking recognition and maintaining their sense of self-worth. It advances the empirical exploration of the agentic component of vulnerability by revealing how the denial of (inter)dependence is presupposed by the conditions of subject-formation.
Examining the association between socio-demographic factors, catheter use and antibiotic prescribing in Northern Ireland primary care: a cross-sectional multilevel analysis
Authors: Nugent C. , Verlander N. Q. , Varma S. , Bradley D. T. , Patterson L.
Published: April 2022

Inappropriate use of antibiotics is among the key drivers of antimicrobial resistance (AMR). Antibiotic use in Northern Ireland (NI) is the highest in the UK and approximately 80% is prescribed in primary care. Little information however exists about the patient and prescriber factors driving this. We described the trend in NI primary care total antibiotic prescribing 2010–2019 and conducted a cross-sectional study using a random sample of individuals registered with an NI GP on 1st January 2019. We used multilevel logistic regression to examine how sociodemographic factors and urinary catheter use was associated with the likelihood of being prescribed an antibiotic during 2019, adjusting for clustering at GP practice and GP federation levels. Finite mixture modelling (FMM) was conducted to determine the association between the aforementioned risk factors and quantity of antibiotic prescribed (defined daily doses). The association between age and antibiotic prescription differed by gender. Compared to males 41–50 years, adjusted odds of prescription were higher for males aged 0–10, 11–20 and 51 + years, and females of any age. Catheter use was strongly associated with antibiotic prescription (aOR = 6.82, 95% CI 2.50–18.64). Socioeconomic deprivation and urban/rural settlement were not associated in the multilevel logistic analysis. GP practices and federations accounted for 1.24% and 0.12% of the variation in antibiotic prescribing respectively. FMM showed associations between larger quantities of antibiotics and being older, male and having a catheter. This work described the profile of individuals most likely to receive an antibiotic prescription in NI primary care and identified GP practice as a source of variation; suggesting an opportunity for reduction from effective interventions targeted at both individuals and general practices.
Forecasting the monthly incidence of scarlet fever in Chongqing, China using the SARIMA model
Authors: Wu W. W. , Li Q. , Tian D. C. , Zhao H. , Xia Y. , Xiong Y. , Su K. , Tang W. G. , Chen X. , Wang J. , Qi L.
Published: April 2022

The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.
The Chinese Antarctic science programme: origins and development
Authors: Zhang Mengzhu , Haward Marcus
Published: April 2022

In 1980, at the invitation of Australia, the first Chinese scientists went to Antarctica. China was therefore a relative ‘latecomer’ to engage in Antarctic science. In the period since its first Antarctic expedition in 1984, China's presence in Antarctica has expanded both in terms of its logistics and infrastructure and its scientific research. This paper outlines the development of China's national Antarctic programmes under the influence of corresponding national policies from the late 1970s to the present, noting the application of various scientific disciplines to Antarctic fields. The paper outlines and analyses the broadening and deepening of China's Antarctic science research, infrastructure and engagement.
Role of DNA repair pathways in the recovery of a dried, radioresistant cyanobacterium exposed to high-LET radiation: implications for the habitability of Mars
Authors: Mosca Claudia , Napoli Alessandro , Fagliarone Claudia , Fujimori Akira , Moeller Ralf , Billi Daniela
Published: April 2022

If life ever appeared on Mars and if it did refuge into sub-superficial environments when surface conditions turned too hostile, then it should have been periodically revived from the frozen, dormant state in order to repair the accumulated damage and reset the survival clock to zero for the next dormant phase. Thus, unravelling how long Earth dormant microorganisms can cope with high-LET radiation mimicking long-term irradiation is fundamental to get insights into the long-term resilience of a dormant microbial life in the Martian subsurface over geological timescales that might have taken advantage of periodically clement conditions that allowed the repair of the accumulated DNA damage. The exposure of dried cells of the radioresistant cyanobacterium Chroococcidiopsis sp. CCMEE 029 to 2 kGy of heavy-ion radiation (Fe ions) did not significantly reduce its survival, although DNA damage was accumulated. Upon rehydration, DNA lesions were repaired as suggested by the over-expression of genes involved in the repair of double strand breaks (DSBs), oxidized bases and apurinic-apyrimidinic sites. Indeed, the monitoring of repair genes upon rehydration suggested a key role of the RecF homologous recombination in repairing DSBs. While the fact that out of the eight genes of the BER system, only one was up-regulated, suggested the absence of DNA lesions generally induced by UV radiation. In conclusion, the non-significantly reduced survival of dried Chroococcidiopsis exposed to 2 kGy of Fe-ion radiation further expanded our appreciation of the resilience of a putative dormant life in the Martian subsurface. Moreover, it is also relevant when searching life on Europa and Enceladus where the radiation environment might critically affect the long-term survival of dormant, frozen life forms.
Bienvenida China: The Role of International Economic Law in China's Economic Relations with Latin America and the Caribbean
Authors: GARCIA Gabriel
Published: April 2022

The first two decades of the twenty-first century saw the rapid rise of China in the global stage. During this period, China acquired valuable knowledge and expertise in International Economic Law (IEL), and expanded its trade and investments across the globe. The emergence of China has benefitted many countries in Latin America and the Caribbean (LAC) in terms of trade and investment; however, it is unclear whether IEL has contributed with the expansion of China's economic relations with LAC. This article aims to address this question by reviewing the strategies and mechanisms employed by China to promote trade, investment and development finance in the region. Its central argument is that China has opted to engage with LAC using an eclectic platform that combines hard law instruments and institutions as well as other soft law mechanisms.
Interhemispheric Asymmetries in Ionospheric Electron Density Responses During Geomagnetic Storms: A Study Using Space‐Based and Ground‐Based GNSS and AMPERE Observations
Authors: Swarnalingam N. , Wu D. L. , Gopalswamy N.
Published: April 2022

We utilize Total Electron Content (TEC) measurements and electron density (Ne) retrieval profiles from Global Navigation Satellite System (GNSS) receivers onboard multiple Low Earth Orbit (LEO) satellites to characterize large‐scale ionosphere‐thermosphere system responses during geomagnetic storms. We also analyze TEC measurements from GNSS receivers in a worldwide ground‐based network. Measurements from four storms during June and July 2012 (boreal summer months), December 2015 (austral summer month), and March 2015 (equinoctial month) are analyzed to study global ionospheric responses and the interhemispheric asymmetry of these responses. We find that the space‐based and ground‐based TECs and their responses are consistent in all four geomagnetic storms. The global 3D view from GNSS‐Radio Occultation (RO) Ne observations captures enhancements and the uplifting of Ne structures at high latitudes during the initial and main phases. Subsequently, Ne depletion occurs at high latitudes and starts progressing into midlatitude and low latitude as the storm reaches its recovery phase. A clear time lag is evident in the storm‐induced Ne perturbations at high latitudes between the summer and winter hemispheres. The interhemispheric asymmetry in TEC and Ne appears to be consistent with the magnitudes of the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) high latitude integrated field‐aligned currents (FACs), which are 3–4 MA higher in the summer hemisphere than in the winter hemisphere during these storms. The ionospheric TEC and Ne responses combined with the AMPERE‐observed FACs indicate that summer preconditioning in the ionosphere‐thermosphere system plays a key role in the interhemispheric asymmetric storm responses.
Influence of Fluid Distribution on Seismic Dispersion and Attenuation in Partially Saturated Limestone
Authors: Sun Chao , Fortin Jérôme , Borgomano Jan V. M. , Wang Shangxu , Tang Genyang , Bultreys Tom , Cnudde Veerle
Published: April 2022

Quantitatively assessing attenuation and dispersion of elastic‐wave velocities in partially saturated reservoir is difficult because of its sensitivity to fluid distribution. We conducted experiments on homogeneous Indiana limestone samples, partially saturated by two methods: drying and imbibition which lead to different fluid distribution for a given saturation. Forced oscillations (from 0.004 to 100 Hz) and ultrasonic (1 MHz) measurements were done under confining pressure to measure the change of elastic moduli with frequency and their attenuation. Our measurements show that compressional (P‐)velocities are strongly sensitive to the sample’s saturation method. For high saturations (above 80%), obtained by drainage, compressional velocities are frequency dependent, and clear peaks of attenuation can be observed. However, at the same saturations obtained by imbibition, no dispersion or attenuation is observed. In addition, shear velocities show little variation with frequency, saturations, and fluid distribution. The dispersion and attenuation of P‐velocities are shown to be influenced by the pore fluid distribution, which was investigated using micro‐computer‐assisted tomographic (CT) scans. Furthermore, a numerical model developed within the framework of poroelasticity’s theory predicts well the experimental results, using the fluid distribution obtained from CT as an input. Our results show that the velocity dispersion was related to wave‐induced fluid flow at mesoscopic scale controlled by the geometry and distribution of the gas patches.
Closed Fluxtubes and Dispersive Proton Conics at Jupiter's Polar Cap
Authors: Szalay J. R. , Clark G. , Livadiotis G. , McComas D. J. , Mitchell D. G. , Rankin J. S. , Sulaiman A. H. , Allegrini F. , Bagenal F. , Ebert R. W. , Gladstone G. R. , Kurth W. S. , Mauk B. H. , Valek P. W. , Wilson R. J. , Bolton S. J.
Published: April 2022

Two distinct proton populations are observed over Jupiter's southern polar cap: a ∼1 keV core population and ∼1–300 keV dispersive conic population at 6–7 RJ planetocentric distance. We find the 1 keV core protons are likely the seed population for the higher‐energy dispersive conics, which are accelerated from a distance of ∼3–5 RJ. Transient wave‐particle heating in a “pressure‐cooker” process is likely responsible for this proton acceleration. The plasma characteristics and composition during this period show Jupiter's polar‐most field lines can be topologically closed, with conjugate magnetic footpoints connected to both hemispheres. Finally, these observations demonstrate energetic protons can be accelerated into Jupiter's magnetotail via wave‐particle coupling.
EMIC Waves Observed Throughout the Inner Magnetosphere Driven by Abrupt Enhancement of the Solar Wind Pressure
Authors: Xue Zuxiang , Yuan Zhigang , Yu Xiongdong , Deng Dan , Huang Zheng , Raita T.
Published: April 2022

Electromagnetic ion cyclotron (EMIC) waves were simultaneously observed in the day‐ and night‐side region driven by a sudden enhancement of the solar wind pressure on 12 July 2013, which was registered by both ground stations and space satellites. The amplitude enhancements of EMIC waves are well correlated to the intensification of the ambient magnetic field caused by the enhanced solar wind pressure pulse. Due to the northward interplanetary magnetic field, the magnetic field intensification is found to appear globally in the inner magnetosphere, which is predicted by field model outputs and evidenced by satellite observations. As a result, the observed nightside protons become more anisotropic, which further promotes proton instabilities and amplifies pre‐existing EMIC waves. Our findings provide direct observational evidence that enhanced solar wind pressure pulse can directly drive the ring current ion dynamics and EMIC wave evolutions throughout the inner magnetosphere.
The Use of Invalid Polar Cap South (PCS) Indices in Publications
Authors: Stauning Peter
Published: April 2022

Polar Cap (PC) indices, PCN North based on magnetic observations from Qaanaaq (THL) in Greenland and PCS South based on magnetic data from Vostok in Antarctica, are very useful indices for studies of solar wind‐magnetosphere interactions and for space weather monitoring and forecasts. PCN indices are issued from the Danish Space Research Institute (DTU Space) while PCS indices are issued from the Arctic and Antarctic Research Institute (AARI) in St Petersburg. Unfortunately, series of invalid PCS values have been provided from AARI and used in a number of publications issued since the PC index concept was endorsed by the International Association of Geomagnetism and Aeronomy (IAGA) in 2013. In spite of the disclosure of the failure in the PCS indices in 2018, publishing at the IAGA‐supported International Service of Geomagnetic Indices of the invalid indices has continued up to now (2022). The present contribution defines the invalidating features of the PCS indices in question, conveys examples, and discusses the applications in peer‐reviewed publications.
Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer
Authors: Elomaa Hanna , Ahtiainen Maarit , Väyrynen Sara A. , Ogino Shuji , Nowak Jonathan A. , Friman Marjukka , Helminen Olli , Wirta Erkki-Ville , Seppälä Toni T. , Böhm Jan , Mäkinen Markus J. , Mecklin Jukka-Pekka , Kuopio Teijo , Väyrynen Juha P.
Published: April 2022

Background

Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities.

Methods

We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell proximity score).

Results

High T cell proximity score associated with longer cancer-specific survival in both the study cohort [adjusted HR for high (vs. low) 0.33, 95% CI 0.20–0.52,Ptrend < 0.0001] and the validation cohort [adjusted HR for high (vs. low) 0.15, 95% CI 0.05–0.45,Ptrend < 0.0001] and its prognostic value was independent of T cell density score.

Conclusions

The spatial point pattern analysis of tumour cell-T cell co-localisation could provide detailed information on colorectal cancer prognosis, supporting the value of spatial measurement of T cell infiltrates as a novel, robust tumour-immune biomarker.
Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations
Authors: Greenough Mark A. , Lane Darius J. R. , Balez Rachelle , Anastacio Helena Targa Dias , Zeng Zhiwen , Ganio Katherine , McDevitt Christopher A. , Acevedo Karla , Belaidi Abdel Ali , Koistinaho Jari , Ooi Lezanne , Ayton Scott , Bush Ashley I.
Published: April 2022

Mutations in presenilin 1 and 2 (PS1 and PS2) cause autosomal dominant familial Alzheimer’s disease (FAD). Ferroptosis has been implicated as a mechanism of neurodegeneration in AD since neocortical iron burden predicts Alzheimer’s disease (AD) progression. We found that loss of the presenilins dramatically sensitizes multiple cell types to ferroptosis, but not apoptosis. FAD causal mutations of presenilins similarly sensitizes cells to ferroptosis. The presenilins promote the expression of GPX4, the selenoprotein checkpoint enzyme that blocks ferroptosis by quenching the membrane propagation of lethal hydroperoxyl radicals. Presenilin γ-secretase activity cleaves Notch-1 to signal LRP8 expression, which then controls GPX4 expression by regulating the supply of selenium into the cell since LRP8 is the uptake receptor for selenoprotein P. Selenium uptake is thus disrupted by presenilin FAD mutations, suppressing GPX4 expression. Therefore, presenilin mutations may promote neurodegeneration by derepressing ferroptosis, which has implications for disease-modifying therapeutics.
Activation of FXR and inhibition of EZH2 synergistically inhibit colorectal cancer through cooperatively accelerating FXR nuclear location and upregulating CDX2 expression
Authors: Yu Junhui , Yang Kui , Zheng Jianbao , Zhao Pengwei , Xia Jie , Sun Xuejun , Zhao Wei
Published: April 2022

Our previous study indicated that colon cancer cells varied in sensitivity to pharmacological farnesoid X receptor (FXR) activation. Herein, we explore the regulatory mechanism of FXR in colorectal cancer (CRC) development and aim to design effective strategies of combined treatment based on the regulatory axis. We found that the expression of FXR was negatively correlated with enhancer of zeste homolog 2 (EZH2) in colon cancer tissues. EZH2 transcriptionally suppressed FXR via H3K27me3. The combination of FXR agonist OCA plus EZH2 inhibitor GSK126 acted in a synergistic manner across four colon cancer cells, efficiently inhibiting clonogenic growth and invasion in vitro, retarding tumor growth in vivo, preventing the G0/G1 to S phase transition, and inducing caspase-dependent apoptosis. Benign control cells FHC were growth-arrested without apoptosis induction, but retained long-term proliferation and invasion capacity. Mechanistically, the drug combination dramatically accelerated FXR nuclear location and cooperatively upregulated caudal-related homeobox transcription factor 2 (CDX2) expression. The depletion of CDX2 antagonized the synergistic effects of the drug combination on tumor inhibition. In conclusion, our study demonstrated histone modification-mediated FXR silencing by EZH2 in colorectal tumorigenesis, which offers useful evidence for the clinical use of FXR agonists combined with EZH2 inhibitors in combating CRC.
VDAC1 regulates neuronal cell loss after retinal trauma injury by a mitochondria-independent pathway
Authors: de Sousa Erica , Móvio Marília Inês , de Lima-Vasconcellos Théo Henrique , dos Santos Gabrieli Bovi , dos Santos Gomes Talita , Walter Lais Takata , da Silva Daniela Almeida , Rodrigues Tiago , Cerchiaro Giselle , Kihara Alexandre Hiroaki
Published: April 2022

The voltage-dependent anion channel 1 (VDAC1) was first described as a mitochondrial porin that mediates the flux of metabolites and ions, thereby integrating both cell survival and death signals. In the nervous system, the functional roles of VDAC1 remain poorly understood. Herein, the rat retina was employed to study VDAC1. First, it was observed that even subtle changes in VDAC1 levels affect neuronal survival, inducing severe alterations in the retinal morphology. We next examined the regulation of VDAC1 after traumatic retinal injury. After mechanical trauma, SOD1 translocates towards the nucleus, which is insufficient to contain the consequences of oxidative stress, as determined by the evaluation of protein carbonylation. Using in vitro models of oxidative stress and mechanical injury in primary retinal cell cultures, it was possible to determine that inhibition of VDAC1 oligomerization by 4′-diisothiocyano-2,2′-disulfonic acid stilbene (DIDS) rescues cell viability, impacting microglial cell activation. We next focused on the regulation of VDAC1 after retinal mechanical injury. VDAC1 was promptly upregulated 2 h after lesion in the plasma membrane and endoplasmic reticulum rather than in the mitochondria, and multimers of VDAC1 were assembled after lesion. DIDS intraocular application decreased apoptosis and prevented microglial polarization, which confirmed in vitro observations. Considering the role of microglia in neuroinflammation, multiplex evaluation of cytokines showed that DIDS application disorganized the inflammatory response 2 h after the lesion, matching the fast regulation of VDAC1. Taken together, data disclosed that fine regulation of VDAC1 influences neuronal survival, and pharmacological inhibition after trauma injury has neuroprotective effects. This protection may be attributed to the effects on VDAC1 abnormal accumulation in the plasma membrane, thereby controlling the activation of microglial cells. We concluded that VDAC1 is a putative therapeutic target in neuronal disorders since it integrates both death and survival cellular signaling.
Long noncoding RNA ZFP36L2-AS functions as a metabolic modulator to regulate muscle development
Authors: Cai Bolin , Ma Manting , Zhang Jing , Kong Shaofen , Zhou Zhen , Li Zhenhui , Abdalla Bahareldin Ali , Xu Haiping , Zhang Xiquan , Lawal Raman Akinyanju , Nie Qinghua
Published: April 2022

Skeletal muscle is the largest metabolic organ in the body, and its metabolic flexibility is essential for maintaining systemic energy homeostasis. Metabolic inflexibility in muscles is a dominant cause of various metabolic disorders, impeding muscle development. In our previous study, we found lncRNAZFP36L2-AS(for “ZFP36L2-antisense transcript”) is specifically enriched in skeletal muscle. Here, we report thatZFP36L2-ASis upregulated during myogenic differentiation, and highly expressed in breast and leg muscle. In vitro,ZFP36L2-ASinhibits myoblast proliferation but promotes myoblast differentiation. In vivo,ZFP36L2-ASfacilitates intramuscular fat deposition, as well as activates fast-twitch muscle phenotype and induces muscle atrophy. Mechanistically,ZFP36L2-ASinteracts with acetyl-CoA carboxylase alpha (ACACA) and pyruvate carboxylase (PC) to induce ACACA dephosphorylation and damaged PC protein stability, thus modulating muscle metabolism. Meanwhile,ZFP36L2-AScan activate ACACA to reduce acetyl-CoA content, which enhances the inhibition of PC activity. Our findings present a novel model about the regulation of lncRNA on muscle metabolism.
HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
Authors: Qin Tao , Xiao Ying , Qian Weikun , Wang Xueni , Gong Mengyuan , Wang Qiqi , An Rui , Han Liang , Duan Wanxing , Ma Qingyong , Wang Zheng
Published: April 2022

Perineural invasion (PNI) is a pathologic feature of pancreatic cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway facilitates the PNI of pancreatic cancer. In this study, we confirmed that c-Met expression was correlated with PNI in pancreatic cancer tissues. Activating the HGF/c-Met signaling pathway potentiated the expression of nerve growth factor (NGF) to recruit nerves and promote the PNI. Activating the HGF/c-Met signaling pathway also enhanced the migration and invasion ability of cancer cells to facilitate cancer cells invading nerves. Mechanistically, HGF/c-Met signaling pathway can active the mTOR/NGF axis to promote the PNI of pancreatic cancer. Additionally, we found that knocking down c-Met expression inhibited cancer cell migration along the nerve, reduced the damage of the sciatic nerve caused by cancer cells and protected the function of the sciatic nerve in vivo. Taken together, our findings suggest a supportive mechanism of the HGF/c-Met signaling pathway in promoting PNI by activating the mTOR/NGF axis in pancreatic cancer. Blocking the HGF/c-Met signaling pathway may be an effective target for the treatment of PNI.
Integrated DNA and RNA sequencing reveals early drivers involved in metastasis of gastric cancer
Authors: Zhang Jieyun , Liu Fatao , Yang Yanan , Yu Nuoya , Weng Xiaoling , Yang Yue , Gong Zhe , Huang Shenglin , Gan Lu , Sun Sijie , Zhang Xiaowei , Gong Yiwei , Liu Yun , Guo Weijian
Published: April 2022

Gastric cancer (GC) is the second cause of cancer-related death and metastasis is an important cause of death. Considering difficulties in searching for metastatic driver mutations, we tried a novel strategy here. We conducted an integrative genomic analysis on GC and identified early drivers lead to metastasis. Whole-exome sequencing (WES), transcriptomes sequencing and targeted-exome sequencing (TES) were performed on tumors and matched normal tissues from 432 Chinese GC patients, especially the comparative analysis between higher metastatic-potential (HMP) group with T1 stage and lymph-node metastasis, and lower metastatic-potential (LMP) group without lymph-nodes or distant metastasis. HMP group presented higher mutation load and heterogeneity, enrichment in immunosuppressive signaling, more immune cell infiltration than LMP group. An integrated mRNA-lncRNA signature based on differentially expressed genes was constructed and its prognostic value was better than traditional TNM stage. We identified 176 candidate prometastatic mutations by WES and selected 8 genes for following TES. Mutated TP53 and MADCAM1 were significantly associated with poor metastasis-free survival. We further demonstrated that mutated MADCAM1 could not only directly promote cancer cells migration, but also could trigger tumor metastasis by establishing immunosuppressive microenvironment, including promoting PD-L1-mediated immune escape and reprogramming tumor-associated macrophages by regulating CCL2 through Akt/mTOR axis. In conclusion, GCs with different metastatic-potential are distinguishable at the genetic level and we revealed a number of potential metastatic driver mutations. Driver mutations in early-onset metastatic GC could promote metastasis by establishing an immunosuppressive microenvironment. This study provided possibility for future target therapy of GC.
Curving the space by non-Hermiticity
Authors: Lv Chenwei , Zhang Ren , Zhai Zhengzheng , Zhou Qi
Published: April 2022

Quantum systems are often classified into Hermitian and non-Hermitian ones. Extraordinary non-Hermitian phenomena, ranging from the non-Hermitian skin effect to the supersensitivity to boundary conditions, have been widely explored. Whereas these intriguing phenomena have been considered peculiar to non-Hermitian systems, we show that they can be naturally explained by a duality between non-Hermitian models in flat spaces and their counterparts, which could be Hermitian, in curved spaces. For instance, prototypical one-dimensional (1D) chains with uniform chiral tunnelings are equivalent to their duals in two-dimensional (2D) hyperbolic spaces with or without magnetic fields, and non-uniform tunnelings could further tailor local curvatures. Such a duality unfolds deep geometric roots of non-Hermitian phenomena, delivers an unprecedented routine connecting Hermitian and non-Hermitian physics, and gives rise to a theoretical perspective reformulating our understandings of curvatures and distance. In practice, it provides experimentalists with a powerful two-fold application, using non-Hermiticity to engineer curvatures or implementing synthetic curved spaces to explore non-Hermitian quantum physics.
USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma
Authors: Ning Zhen , Guo Xin , Liu Xiaolong , Lu Chang , Wang Aman , Wang Xiaolin , Wang Wen , Chen Huan , Qin Wangshu , Liu Xinyu , Zhou Lina , Ma Chi , Du Jian , Lin Zhikun , Luo Haifeng , Otkur Wuxiyar , Qi Huan , Chen Di , Xia Tian , Liu Jiwei , Tan Guang , Xu Guowang , Piao Hai-long
Published: April 2022

Elevated de novo lipogenesis is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. Herein, we identify ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with deubiquitinates and stabilizes peroxisome proliferator-activated receptor gamma (PPARγ) through K48-linked deubiquitination, and in turn, this stabilization increases acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACLY) expressions. In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments. In HCC, high expression of USP22 positively correlates with PPARγ, ACLY or ACC expression, and associates with a poor prognosis. Taken together, we identify a USP22-regulated lipogenesis mechanism that involves the PPARγ-ACLY/ACC axis in HCC tumorigenesis and provide a rationale for therapeutic targeting of lipogenesis via USP22 inhibition.
Dual-comb photothermal spectroscopy
Authors: Wang Qiang , Wang Zhen , Zhang Hui , Jiang Shoulin , Wang Yingying , Jin Wei , Ren Wei
Published: April 2022

Dual-comb spectroscopy (DCS) has revolutionized optical spectroscopy by providing broadband spectral measurements with unprecedented resolution and fast response. Photothermal spectroscopy (PTS) with a pump-probe configuration offers a highly sensitive gas sensing method, which is normally performed using a single-wavelength pump laser. The merging of PTS with DCS may enable a spectroscopic method by taking advantage of both technologies, which has never been studied yet. Here, we report dual-comb photothermal spectroscopy (DC-PTS) by passing dual combs and a probe laser through a gas-filled anti-resonant hollow-core fiber, where the generated multi-heterodyne modulation of the refractive index is sensitively detected by an in-line interferometer. As an example, we have measured photothermal spectra of acetylene over 1 THz, showing a good agreement with the spectral database. Our proposed DC-PTS provides opportunities for broadband gas sensing with super-fine resolution and high sensitivity, as well as with a small sample volume and compact configuration.
KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling
Authors: Yu Bo , Su Jun , Shi Qiqi , Liu Qing , Ma Jun , Ru Guoqing , Zhang Lei , Zhang Jian , Hu Xichun , Tang Jianming
Published: April 2022

Smad nuclear-interacting protein 1 (SNIP1) is a transcription repressor related to the TGF-β signaling pathway and associates with c-MYC, a key regulator of cell proliferation and tumor development. Currently, the mechanism by which SNIP1 regulates tumorigenesis and cancer metastasis is unknown. Here, we identify that SNIP1 is a non-histone substrate of lysine methyltransferase KMT5A, which undergoes KMT5A-mediated mono-methylation to promote breast cancer cell growth, invasion and lung metastasis. Mechanistically, we show KMT5A-mediated K301 methylation of SNIP1 represents a sensing signal to release histone acetyltransferase KAT2A and promotes the interaction of c-MYC and KAT2A, and the recruitment of c-MYC/KAT2A complex to promoter of c-MYC targets. This event ultimately inhibits the Hippo kinase cascade to enhance triple-negative breast cancer (TNBC) metastasis by transcriptionally activating MARK4. Co-inhibition of KMT5A catalytic activity and YAP in TNBC xenograft-bearing animals attenuates breast cancer metastasis and increases survival. Collectively, this study presents an KMT5A methylation-dependent regulatory mechanism governing oncogenic function of SNIP1.
Strong pairing in mixed-dimensional bilayer antiferromagnetic Mott insulators
Authors: Bohrdt Annabelle , Homeier Lukas , Bloch Immanuel , Demler Eugene , Grusdt Fabian
Published: April 2022

Interacting many-body systems in reduced-dimensional settings, such as ladders and few-layer systems, are characterized by enhanced quantum fluctuations. Recently, two-dimensional bilayer systems have sparked considerable interest because they can host unusual phases, including unconventional superconductivity. Here we present a theoretical proposal for realizing high-temperature pairing of fermions in a class of bilayer Hubbard models. We introduce a general and highly efficient pairing mechanism for mobile charge carriers in doped antiferromagnetic Mott insulators. The pairing is caused by the energy that one charge gains when it follows the path created by another charge. We show that this mechanism leads to the formation of highly mobile but tightly bound pairs in the case of mixed-dimensional Fermi–Hubbard bilayer systems. This setting is closely related to the Fermi–Hubbard model believed to capture the physics of copper oxides, and can be realized in currently available ultracold atom experiments.
Recombinant Fsh and Lh therapy for spawning induction of previtellogenic and early spermatogenic arrested teleost, the flathead grey mullet (Mugil cephalus)
Authors: Ramos-Júdez Sandra , Giménez Ignacio , Gumbau-Pous Josep , Arnold-Cruañes Lucas Stephen , Estévez Alicia , Duncan Neil
Published: April 2022

With the expansion and diversification of global aquaculture, efforts continue to develop new bio-technologies for assisted reproduction in species that present reproductive dysfunctions. Flathead grey mullet (Mugil cephalus) males held in intensive conditions in the Mediterranean region do not produce fluent milt and most females are arrested at previtellogenesis. The weekly injections of recombinant follicle stimulating hormone (rFsh) and luteinizing hormone (rLh) induced and completed vitellogenesis in treated females (n = 21), and treated males produced fluent sperm (n = 9). The application of a priming dose of 30 µg kg−1 rLh and resolving dose of 40 mg kg−1 Progesterone, or priming and resolving doses of 30 µg kg−1 rLh, resulted in the induction of maturation, ovulation, and spontaneous spawns with a spawning success of the 85% (8 of 9 females) and 100% (n = 6), respectively. The eggs collected had 63 ± 21% fertilization with embryo development and 58 ± 23% hatching. In comparison, control individuals did not show advances in gonadal development and did not produce fluent sperm. The present results confirm the possibility of controlling oogenesis from previtellogenesis to the completion of maturation and fertilised tank spawning using exclusively rFsh and rLh in a teleost species.
Gene profiling of SEC13, SMAD7, GHRL, long non-coding RNA GHRLOS, HIF-1α in gastric cancer patients
Authors: Hussein Neveen A. , Rashad Mona M. , Abdou Azza S. , Hussein Amr M. , Mohamed Hagar M.
Published: April 2022

Even with considerable progress in cancer researches, gastric cancer is still one of the global health problems. Recognition of the differential expressed genes in GC is the most appropriate approach for establishing new diagnostic targets. This study evaluates SEC13, SMAD7, GHRL, lncRNA GHRLOS, HIF-1α genes profiling as well as HIF-1α protein level for GC. The expression of selected genes, serum HIF-1α and CEA protein levels were determined for 50 GC patients and 50 healthy controls by real-time RT-PCR, ELISA, and ELICA respectively. The sensitivities of these parameters as diagnostic biomarkers were evaluated. SMAD7, HIF-1α expression, serum HIF-1α, and CEA level were significantly upregulated in GC patients as compared to the control group (P = 0.024, < 0.001) and had significant positive correlations between each other except SMAD7 with serum HIF-1α, and CEA level. On the other hand, SEC13, GHRL, and lncRNA GHRLOS expression were significantly downregulated in GC patients (P =  < 0.001, 0.025, < 0.001 respectively) and had significant positive correlations with each other (P < 0.001). Significant negative correlations were observed between most of both groups. All studied parameters were associated with GC clinical stages except SMAD7 was associated with stage IV only (P = 0.005) and GHRL did not associate with tumor stages (P ˃ 0.05). All studied parameters may be promising biomarkers for the early diagnosis of GC. SMAD7, HIF-1α gene, and HIF-1α protein may be jointly implicated in cancer development and prognosis, while SEC13, GHRL, and lncRNA GHRLOS may act as tumor suppressors.
Clinical diagnosis of metabolic disorders using untargeted metabolomic profiling and disease-specific networks learned from profiling data
Authors: Thistlethwaite Lillian R. , Li Xiqi , Burrage Lindsay C. , Riehle Kevin , Hacia Joseph G. , Braverman Nancy , Wangler Michael F. , Miller Marcus J. , Elsea Sarah H. , Milosavljevic Aleksandar
Published: April 2022

Untargeted metabolomics is a global molecular profiling technology that can be used to screen for inborn errors of metabolism (IEMs). Metabolite perturbations are evaluated based on current knowledge of specific metabolic pathway deficiencies, a manual diagnostic process that is qualitative, has limited scalability, and is not equipped to learn from accumulating clinical data. Our purpose was to improve upon manual diagnosis of IEMs in the clinic by developing novel computational methods for analyzing untargeted metabolomics data. We employed CTD, an automated computational diagnostic method that “connects the dots” between metabolite perturbations observed in individual metabolomics profiling data and modules identified in disease­specific metabolite co-perturbation networks learned from prior profiling data. We also extended CTD to calculate distances between any two individuals (CTDncd) and between an individual and a disease state (CTDdm), to provide additional network-quantified predictors for use in diagnosis. We show that across 539 plasma samples, CTD-based network-quantified measures can reproduce accurate diagnosis of 16 different IEMs, including adenylosuccinase deficiency, argininemia, argininosuccinic aciduria, aromatic l-amino acid decarboxylase deficiency, cerebral creatine deficiency syndrome type 2, citrullinemia, cobalamin biosynthesis defect, GABA-transaminase deficiency, glutaric acidemia type 1, maple syrup urine disease, methylmalonic aciduria, ornithine transcarbamylase deficiency, phenylketonuria, propionic acidemia, rhizomelic chondrodysplasia punctata, and the Zellweger spectrum disorders. Our approach can be used to supplement information from biochemical pathways and has the potential to significantly enhance the interpretation of variants of uncertain significance uncovered by exome sequencing. CTD, CTDdm, and CTDncd can serve as an essential toolset for biological interpretation of untargeted metabolomics data that overcomes limitations associated with manual diagnosis to assist diagnosticians in clinical decision-making. By automating and quantifying the interpretation of perturbation patterns, CTD can improve the speed and confidence by which clinical laboratory directors make diagnostic and treatment decisions, while automatically improving performance with new case data.
Comparison of sequential CT arterioportography-arteriosplenography with standard cross-sectional imaging and endoscopy in children with portal hypertension
Authors: Hammer Simone , Zeman Florian , Schlitt Hans Jürgen , Stroszczynski Christian , Greiner Barbara , Doppler Michael Christian , Uller Wibke
Published: April 2022

In this study the diagnostic capability and additional value of sequential CT arterioportography–arteriosplenography (CT AP–AS) in comparison to standard cross-sectional imaging and upper gastrointestinal endoscopy (UGE) in pediatric portal hypertension (PH) was analyzed. Patients with clinical signs of PH who underwent CT AP–AS in combination with additional contrast-enhanced magnetic resonance imaging (CE-MR) and/or contrast-enhanced computed tomography (CE-CT) were included. Two radiologists reviewed independently imaging regarding the capability to prove patency of (1) extrahepatic and intrahepatic main stem portal vein (PV), (2) intrahepatic PV system and (3) splenomesenteric venous axis. Imaging was reviewed for detection of abdominal varices and results were compared to UGE. Main venous supply of varices (PV and/or splenic vein system) and splenorenal shunting were evaluated. 47 imaging studies (20 CT AP-AS, 16 CE-MR, 11 CE-CT) and 12 UGE records of 20 patients were analyzed. CT AP–AS detected significantly more splenorenal shunts (p = 0.008) and allowed more confident characterization of the extra-/intrahepatic PV-system and splenomesenteric veins in comparison to CE-MR (p < 0.001). Extra- and intrahepatic PV-system were significantly more confidently assessed in CT AP–AS than in CE-CT (p = 0.008 and < 0.001 respectively). CT AP–AS was the only modality that detected supply of varices and additional gastric/duodenal varices. In this retrospective study CT AP–AS was superior to standard cross-sectional imaging concerning confident assessment of the venous portosplenomesenteric axis in pediatric patients. CT AP–AS detected additional varices, splenorenal shunting and supply of varices.
Transient elastography and serum markers of liver fibrosis associate with epicardial adipose tissue and coronary artery calcium in NAFLD
Authors: Perdomo Carolina M. , Ezponda Ana , Núñez-Córdoba Jorge M. , Herrero José I. , Bastarrika Gorka , Frühbeck Gema , Escalada Javier
Published: April 2022

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.
Coriander (Coriandrum sativum L.) essential oil and oil-loaded nano-formulations as an anti-aging potentiality via TGFβ/SMAD pathway
Authors: Salem Mohamed A. , Manaa Eman G. , Osama Nada , Aborehab Nora M. , Ragab Mai F. , Haggag Yusuf A. , Ibrahim Magda T. , Hamdan Dalia I.
Published: April 2022

Aging has become a concern for many people, especially women. Given that high-quality anti-aging products are of high cost; it has imperative to search for other economical sources. Essential oils are frequently used in cosmetics products due to a wide range of biological activities as well as their pleasant odor. The current study aimed to investigate the biochemical effect of the cosmetic potential of selected Apiaceous essential oils, traditionally used for skincare, by evaluating their anti-wrinkle activity. It is worth noting that, coriander essential oil showed the highest collagenase, elastase, tyrosinase, and hyaluronidase inhibitory activities compared to other Apiaceous oils (fennel, anise, and cumin). GC–MS proved that coriander essential oil showed a very high level of oxygenated monoterpenes, with linalool (81.29%) as the most abundant constituent. Intriguingly, coriander oil cream and Coriander Essential Oil-loaded Lipid Nanoparticles (CEOLNs) formulations attenuated in vivo UV-induced skin photoaging that was manifested by significantly decreased MDA, COX-2, PGE-2, MMP-1, JNK, and AP-1 levels. Moreover, these pharmaceutical dosage forms significantly increased skin collagen content compared to UV-injured group. Also, coriander essential oil significantly increased TGFβ, TGFβII, and SMAD3 protein expression levels compared to UV-injured group. In conclusion, the pharmaceutical dosage forms of coriander oil possess anti-wrinkle activities that could have an auspicious role in amending extrinsic aging.