bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic analysis reveals hub genes and pathways in response to acetic acid stress in Kluyveromyces marxianus during high-temperature ethanol fermentation
Authors: Li Yumeng , Hou Shiqi , Ren Ziwei , Fu Shaojie , Wang Sunhaoyu , Chen Mingpeng , Dang Yan , Li Hongshen , Li Shizhong , Li Pengsong
Published: July 2023

The thermotolerant yeast Kluyveromyces marxianus is known for its potential in high-temperature ethanol fermentation, yet it suffers from excess acetic acid production at elevated temperatures, which hinders ethanol production. To better understand how the yeast responds to acetic acid stress during high-temperature ethanol fermentation, this study investigated its transcriptomic changes under this condition. RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) and enriched gene ontology (GO) terms and pathways under acetic acid stress. The results showed that 611 genes were differentially expressed, and GO and pathway enrichment analysis revealed that acetic acid stress promoted protein catabolism but repressed protein synthesis during high-temperature fermentation. Protein–protein interaction (PPI) networks were also constructed based on the interactions between proteins coded by the DEGs. Hub genes and key modules in the PPI networks were identified, providing insight into the mechanisms of this yeast's response to acetic acid stress. The findings suggest that the decrease in ethanol production is caused by the imbalance between protein catabolism and protein synthesis. Overall, this study provides valuable insights into the mechanisms of K. marxianus's response to acetic acid stress and highlights the importance of maintaining a proper balance between protein catabolism and protein synthesis for high-temperature ethanol fermentation.
Existence and Decay Estimates of Solution for a Fourth Order Quasi-Geostrophic Equation
Authors: Li Huiling , Li Jing , Zhang Jingjun
Published: July 2023

This paper considers a single-layer fourth order quasi-geostrophic equation in two-dimensional case. We prove the existence and uniqueness of global smooth solution to the Cauchy problem of this equation by using energy estimate. We also establish a new estimate for the nonlinear term and obtain decay estimates of the solution in $$L^{2}$$

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2

.
Indicators of improved gestation housing of sows. Part I: Effects on behaviour, skin lesions, locomotion, and tear staining
Authors: Lagoda Martyna E , O’Driscoll Keelin , Galli Maria C , Marchewka Joanna , Boyle Laura A
Published: July 2023

Commercial gestation housing systems for sows generally fail to cater fully for their needs in terms of comfort or the ability to perform highly motivated behaviours, which can lead to chronic stress and an impairment to welfare. We compared a typical gestation system (CONTROL) with an IMPROVED one as regards oral stereotypies, aggressive behaviour, skin lesions, locomotion, and tear staining. Sows were mixed into 12 stable groups (six groups per treatment, 20 sows per group), 29 days post-service in pens with free-access, full-length individual feeding/lying stalls. CONTROL pens had fully slatted concrete floors, with two blocks of wood and two chains suspended in the group area. IMPROVED pens were the same but with rubber mats and a length of manila rope in each feeding stall, and straw provided in three racks in the group area. Direct observations of oral stereotypical (30 instantaneous scans per sow per day) and aggressive (all-occurrence sampling, 3 h per sow per day) behaviours were conducted 72 h post-mixing, in mid and late gestation. Skin lesions were counted 24 h and three weeks post-mixing, and in late gestation. Sows’ locomotion (locomotory ability) was scored using a visual analogue scale in mid and late gestation. Right and left eye tear staining was scored in late gestation. Indications of better welfare in IMPROVED sows included performance of fewer oral stereotypies in mid and late gestation, and lower tear stain scores. These sows performed more aggression in late gestation, which was associated with access to enrichment, but skin lesion counts were not affected. Thus, the changes made in the IMPROVED treatment benefitted aspects of sow welfare.
How do innovative internet tech startups attract venture capital financing?
Authors: Zhou Yan , Park Sangmoon , Zhang Justin Zuopeng , Ferreira João J.
Published: July 2023

This research uses signaling theory to combine the perspective of investment results with existing venture capital (VC) standards and reexamines the factors that influence the attractiveness of innovative internet tech startups to VC from the perspective of equal opportunity startups. Taking the financing status of 310 startups in China's sharing economy as an example and using regression analysis, we empirically test the influence of entrepreneur and firm characteristics on attracting VC. Our results show that among founder characteristics, the entrepreneur's entrepreneurial experience alone is insufficient to attract VC. Industrial experience and political background have a positive influence on attracting VC. Among firm characteristics, market-entry order and business group (BG) affiliation positively influence attracting VC. This is a new and relevant discovery. In the Chinese market, investors are more inclined to provide financial support to entrepreneurs or startups that have already gained legitimacy from the government or business groups.
ON REAL NONISOMORPHIC BANACH SPACES WITH HOMEOMORPHIC GEOMETRIC STRUCTURE SPACES
Authors: TANAKA RYOTARO
Published: July 2023

We give an example of a pair of real Banach spaces such that they are neither linearly isomorphic nor isomorphic with respect to the structure of Birkhoff–James orthogonality, but have mutually homeomorphic geometric structure spaces.
God, Über-God, and Unter-God
Authors: Gordon Noah
Published: July 2023

I examine two related arguments for the claim that if God is omnipotent, God cannot lack abilities such as the ability to do evil or to act irrationally. Both arguments concern the idea that omnipotence is inconsistent with being dominated with respect to abilities. I raise new issues in the formulation of such dominance principles about ability, and attempt to solve them. I also discuss and reject existing objections to these arguments. I conclude that these arguments are promising but not conclusive, and that important work remains to be done in formulating the relevant dominance principles.
Physical Activity and Social Interaction among Rural Older Adults in Saskatchewan during COVID-19
Authors: Schmidt Laurie , Johnson Shanthi , Rebecca Genoe M. , Jeffery Bonnie , Crawford Jennifer
Published: July 2023

Physical activity and social interaction among rural older adults are important, particularly during the COVID-19 pandemic when restrictions on physical gatherings were placed. The purpose of this qualitative study was to gain a deeper understanding of rural older adults’ experience with physical activity and social interaction during the COVID-19 pandemic. An interpretative phenomenological approach was used to explore the experience of 10 older adults, 67–82 years of age, from rural communities throughout Saskatchewan. Findings revealed that many rural older adults acknowledged the health benefits of physical and social activities and experienced loneliness when COVID-19 restrictions were placed, even when living with a partner. For some, the restrictions placed on physical and social activity provided a welcome break from daily responsibilities. Rural communities, often at a disadvantage, were also perceived by participants as being protected against COVID-19. The resilience demonstrated among rural participants to persevere and adapt to their changing environment during the pandemic was evident in the findings.
Anger dysregulation and non-suicidal self-injury during adolescence: A test of directionality
Authors: Larsson Johannes , Tilton-Weaver Lauree C. , Zhao Xiang
Published: July 2023

Non-suicidal self-injury (NSSI) has been tied to several forms of emotional and behavioral dysregulation in adolescence, with less attention paid to regulation of anger. Most assume that anger dysregulation leads to engagement in NSSI, rather than the reverse. However, it is plausible that NSSI compromises adolescents’ abilities to regulate their emotions, including anger, because it may reduce the development of alternative regulatory strategies and intensify negative emotions by reducing tolerance of distress. Using three waves of data from a sample of adolescents in 17 Swedish schools (n = 1,304 Mage = 13.68, SDage = .67; 89% of Swedish origin; 58% girls), we examined the directionality of ties between NSSI and three forms of anger dysregulation: dysregulated expressions of anger, anger suppression, and low anger reflection. We also looked for differences in magnitude of paths and gender differences. Random-intercept cross-lagged panel models showed that NSSI predicted changes in all forms of anger dysregulation but found no support for the opposite direction. Gender differences were not evident. Results challenge directionality assumptions and support suggestions that adolescents’ anger regulation degrades when they self-injure.
The Gendered Representational Costs of Violence against Politicians
Authors: Håkansson Sandra
Published: July 2023

Women face more harassment and intimidation as politicians than men, but little is known about how this affects representation. I develop a theoretical framework for studying the gendered costs of political violence for descriptive, substantive, and symbolic representation. Testing the framework using interview and survey data on Swedish women and men politicians, I uncover the costs of violence against politicians in all three dimensions empirically. Violence makes women more frequently than men consider leaving politics and enforces male-coded characteristics for political candidates, affecting prospects for gender-diverse descriptive representation. Substantive representation is harmed by violence silencing feminist debates and obstructing women politicians’ policy debate activities. Women’s symbolic representation is threatened by violence coercing women to decrease their visibility.
Solar‐Synchronous Tides in Mars Thermosphere CO2, Ar, and N2 Densities From MAVEN
Authors: Forbes Jeffrey M. , Zhang Xiaoli , Fang Xiaohua , Benna Mehdi , González‐Galindo Francisco , Forget Francois , Millour Ehouarn
Published: July 2023

Measurements of CO2, Ar and N2 densities from the Neutral Gas and Ion Mass Spectrometer on the Mars Atmosphere and Volatile Evolution Mission (MAVEN) between 150 and 200 km altitude during 2015–2022 are analyzed to reveal diurnal (DW1), semidiurnal (SW2) and terdiurnal (TW3) solar‐synchronous tides in Mars thermosphere. Multi‐year‐mean tidal perturbations on a diurnal‐ and zonal‐mean background, corrected for solar flux variations, are reported as a function of latitude (48°S–48°N), altitude and solar longitude (Ls). The DW1, SW2 and TW3 amplitudes at for example, 180 km altitude are of order 90%–120%, 15%–20%, and ≲10% for CO2 and Ar, and roughly 2/3 these values for N2, the latter presumably due to the difference in molecular weight from the other species. Through examination of vertical phase progressions, DW1 is concluded to be mainly excited in situ, but SW2 and TW3 contain significant contributions from tides propagating upward from lower altitudes. By analogy with studies for Earth's thermosphere, the DW1 amplitudes and phases are thought to reflect the combined influences of thermal expansion and vertical winds. Points of agreement and disagreement with DW1, SW2, and TW3 amplitudes and phases derived from the Mars Climate Database are noted and interpreted.
Controlling the electro-optic response of a semiconducting perovskite coupled to a phonon-resonant cavity
Authors: Di Virgilio Lucia , Geuchies Jaco J. , Kim Heejae , Krewer Keno , Wang Hai , Grechko Maksim , Bonn Mischa
Published: July 2023

Optical cavities, resonant with vibrational or electronic transitions of material within the cavity, enable control of light-matter interaction. Previous studies have reported cavity-induced modifications of chemical reactivity, fluorescence, phase behavior, and charge transport. Here, we explore the effect of resonant cavity-phonon coupling on the transient photoconductivity in a hybrid organic-inorganic perovskite. To this end, we measure the ultrafast photoconductivity response of perovskite in a tunable Fabry–Pérot terahertz cavity, designed to be transparent for optical excitation. The terahertz-cavity field-phonon interaction causes apparent Rabi splitting between the perovskite phonon mode and the cavity mode. We explore whether the cavity-phonon interaction affects the material’s electron-phonon interaction by determining the charge-carrier mobility through photoconductivity. Despite the apparent hybridization of cavity and phonon modes, we show that the perovskite properties in both ground (phonon response) and excited (photoconductive response) states remain unaffected by the tunable light-matter interaction. Yet the response of the integral perovskite-terahertz optical cavity system depends critically on the interaction strength of the cavity with the phonon: the transient terahertz response to optical excitation can be increased up to threefold by tuning the cavity-perovskite interaction strength. These results enable tunable switches and frequency-controlled induced transparency devices.
In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome
Authors: Raven Erika P. , Veraart Jelle , Kievit Rogier A. , Genc Sila , Ward Isobel L. , Hall Jessica , Cunningham Adam , Doherty Joanne , van den Bree Marianne B. M. , Jones Derek K.
Published: July 2023

22q11.2 deletion syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia and autism spectrum disorders, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterization of white matter microstructure in participants with 22q11.2DS (12–15 years) and those undergoing typical development (8–18 years) using a customized magnetic resonance imaging scanner which is sensitive to axonal morphology. A rich array of diffusion MRI metrics are extracted to present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences in individuals with 22q11.2DS. A recent, large-scale consortium study of 22q11.2DS identified higher diffusion anisotropy and reduced overall diffusion mobility of water as hallmark microstructural alterations of white matter in individuals across a wide age range (6–52 years). We observed similar findings across the white matter tracts included in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that abnormal microstructural connectivity in 22q11.2DS may be mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo white matter phenotype of 22q11.2DS, and promote the continued investigation of shared features in neurodevelopmental and psychiatric disorders.
Circulating metabolites modulated by diet are associated with depression
Authors: van der Spek Ashley , Stewart Isobel D. , Kühnel Brigitte , Pietzner Maik , Alshehri Tahani , Gauß Friederike , Hysi Pirro G. , MahmoudianDehkordi Siamak , Heinken Almut , Luik Annemarie I. , Ladwig Karl-Heinz , Kastenmüller Gabi , Menni Cristina , Hertel Johannes , Ikram M. Arfan , de Mutsert Renée , Suhre Karsten , Gieger Christian , Strauch Konstantin , Völzke Henry , Meitinger Thomas , Mangino Massimo , Flaquer Antonia , Waldenberger Melanie , Peters Annette , Thiele Ines , Kaddurah-Daouk Rima , Dunlop Boadie W. , Rosendaal Frits R. , Wareham Nicholas J. , Spector Tim D. , Kunze Sonja , Grabe Hans Jörgen , Mook-Kanamori Dennis O. , Langenberg Claudia , van Duijn Cornelia M. , Amin Najaf
Published: July 2023

Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.
Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies
Authors: Finze Anika , Biechele Gloria , Rauchmann Boris-Stephan , Franzmeier Nicolai , Palleis Carla , Katzdobler Sabrina , Weidinger Endy , Guersel Selim , Schuster Sebastian , Harris Stefanie , Schmitt Julia , Beyer Leonie , Gnörich Johannes , Lindner Simon , Albert Nathalie L. , Wetzel Christian H. , Rupprecht Rainer , Rominger Axel , Danek Adrian , Burow Lena , Kurz Carolin , Tato Maia , Utecht Julia , Papazov Boris , Zaganjori Mirlind , Trappmann Lena-Katharina , Goldhardt Oliver , Grimmer Timo , Haeckert Jan , Janowitz Daniel , Buerger Katharina , Keeser Daniel , Stoecklein Sophia , Dietrich Olaf , Morenas-Rodriguez Estrella , Barthel Henryk , Sabri Osama , Bartenstein Peter , Simons Mikael , Haass Christian , Höglinger Günter U. , Levin Johannes , Perneczky Robert , Brendel Matthias
Published: July 2023

β-amyloid (Aβ) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer’s disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated. We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, Aβ-, tau-, and perfusion-surrogate-PET, as well as structural MRI. Z-score deviations for 246 brain regions were calculated and biomarker contributions of Aβ (A), tau (T), perfusion (N1), and gray matter atrophy (N2) to microglial activation (TSPO, I) were calculated for each individual subject. Individual ATN-related microglial activation was correlated with clinical performance and CSF soluble TREM2 (sTREM2) concentrations. In typical and atypical AD, regional tau was stronger and more frequently associated with microglial activation when compared to regional Aβ (AD: βT = 0.412 ± 0.196 vs. βA = 0.142 ± 0.123, p < 0.001; AD-CBS: βT = 0.385 ± 0.176 vs. βA = 0.131 ± 0.186, p = 0.031). The strong association between regional tau and microglia reproduced well in primary tauopathies (βT = 0.418 ± 0.154). Stronger individual associations between tau and microglial activation were associated with poorer clinical performance. In patients with 4RT, sTREM2 levels showed a positive association with tau-related microglial activation. Tau pathology has strong regional associations with microglial activation in primary and secondary tauopathies. Tau and Aβ related microglial response indices may serve as a two-dimensional in vivo assessment of neuroinflammation in neurodegenerative diseases.
Cancer-associated fibroblasts facilitate breast cancer progression through exosomal circTBPL1-mediated intercellular communication
Authors: Ye Fangzhou , Liang Yiran , Wang Yajie , Le Yang Robert , Luo Dan , Li Yaming , Jin Yuhan , Han Dianwen , Chen Bing , Zhao Wenjing , Wang Lijuan , Chen Xi , Ma Tingting , Kong Xiaoli , Yang Qifeng
Published: July 2023

Breast cancer is the major common malignancy worldwide among women. Previous studies reported that cancer-associated fibroblasts (CAFs) showed pivotal roles in regulating tumor progression via exosome-mediated cellular communication. However, the detailed mechanism underlying the exosomal circRNA from CAFs in breast cancer progression remains ambiguous. Here, exosomal circRNA profiling of breast cancer-derived CAFs and normal fibroblasts (NFs) was detected by high-throughput sequencing, and upregulated circTBPL1 expression was identified in CAF exosomes. The exosomal circTBPL1 from CAFs could be transferred to breast cancer cells and promoted cell proliferation, migration, and invasion. Consistently, circTBPL1 knockdown in CAFs attenuated their tumor-promoting ability. Further exploration identified miR-653-5p as an inhibitory target of circTBPL1, and ectopic expression of miR-653-5p could partially reverse the malignant phenotypes induced by circTBPL1 overexpression in breast cancer. Additionally, TPBG was selected as a downstream target gene, and circTBPL1 could protect TPBG from miR-653-5p-mediated degradation, leading to enhanced breast cancer progression. Significantly, the accelerated tumor progression triggered by exosomal circTBPL1 from CAFs was confirmed in xenograft models. Taken together, these results revealed that exosomal circTBPL1 derived from CAFs contributed to cancer progression via miR-653-5p/TPBG pathway, indicating the potential of exosomal circTBPL1 as a biomarker and novel therapeutic target for breast cancer.
Nitric oxide-induced ribosome collision activates ribosomal surveillance mechanisms
Authors: Ryder Laura , Arendrup Frederic Schrøder , Martínez José Francisco , Snieckute Goda , Pecorari Chiara , Shah Riyaz Ahmad , Lund Anders H. , Blasius Melanie , Bekker-Jensen Simon
Published: July 2023

Impairment of protein translation can cause stalling and collision of ribosomes and is a signal for the activation of ribosomal surveillance and rescue pathways. Despite clear evidence that ribosome collision occurs stochastically at a cellular and organismal level, physiologically relevant sources of such aberrations are poorly understood. Here we show that a burst of the cellular signaling molecule nitric oxide (NO) reduces translational activity and causes ribosome collision in human cell lines. This is accompanied by activation of the ribotoxic stress response, resulting in ZAKα-mediated activation of p38 and JNK kinases. In addition, NO production is associated with ZNF598-mediated ubiquitination of the ribosomal protein RPS10 and GCN2-mediated activation of the integrated stress response, which are well-described responses to the collision of ribosomes. In sum, our work implicates a novel role of NO as an inducer of ribosome collision and activation of ribosomal surveillance mechanisms in human cells.
Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR)
Authors: Nikolaienko Roman , Bovo Elisa , Kahn Daniel , Gracia Ryan , Jamrozik Thomas , Zima Aleksey V.
Published: July 2023

The most common cardiac pathologies, such as myocardial infarction and heart failure, are associated with oxidative stress. Oxidation of the cardiac ryanodine receptor (RyR2) Ca2+ channel causes spontaneous oscillations of intracellular Ca2+, resulting in contractile dysfunction and arrhythmias. RyR2 oxidation promotes the formation of disulfide bonds between two cysteines on neighboring RyR2 subunits, known as intersubunit cross-linking. However, the large number of cysteines in RyR2 has been a major hurdle in identifying the specific cysteines involved in this pathology-linked post-translational modification of the channel. Through mutagenesis of human RyR2 and in-cell Ca2+ imaging, we identify that only two cysteines (out of 89) in each RyR2 subunit are responsible for half of the channel’s functional response to oxidative stress. Our results identify cysteines 1078 and 2991 as a redox-sensitive pair that forms an intersubunit disulfide bond between neighboring RyR2 subunits during oxidative stress, resulting in a pathological “leaky” RyR2 Ca2+ channel.
Enhancing polyol/sugar cascade oxidation to formic acid with defect rich MnO2 catalysts
Authors: Yan Hao , Liu Bowen , Zhou Xin , Meng Fanyu , Zhao Mingyue , Pan Yue , Li Jie , Wu Yining , Zhao Hui , Liu Yibin , Chen Xiaobo , Li Lina , Feng Xiang , Chen De , Shan Honghong , Yang Chaohe , Yan Ning
Published: July 2023

Oxidation of renewable polyol/sugar into formic acid using molecular O2over heterogeneous catalysts is still challenging due to the insufficient activation of both O2and organic substrates on coordination-saturated metal oxides. In this study, we develop a defective MnO2catalyst through a coordination number reduction strategy to enhance the aerobic oxidation of various polyols/sugars to formic acid. Compared to common MnO2, the tri-coordinated Mn in the defective MnO2catalyst displays the electronic reconstruction of surface oxygen charge state and rich surface oxygen vacancies. These oxygen vacancies create more Mnδ+Lewis acid site together with nearby oxygen as Lewis base sites. This combined structure behaves much like Frustrated Lewis pairs, serving to facilitate the activation of O2, as well as C–C and C–H bonds. As a result, the defective MnO2catalyst shows high catalytic activity (turnover frequency: 113.5 h−1) and formic acid yield (>80%) comparable to noble metal catalysts for glycerol oxidation. The catalytic system is further extended to the oxidation of other polyols/sugars to formic acid with excellent catalytic performance.
Accelerating the energy transition towards photovoltaic and wind in China
Authors: Wang Yijing , Wang Rong , Tanaka Katsumasa , Ciais Philippe , Penuelas Josep , Balkanski Yves , Sardans Jordi , Hauglustaine Didier , Liu Wang , Xing Xiaofan , Li Jiarong , Xu Siqing , Xiong Yuankang , Yang Ruipu , Cao Junji , Chen Jianmin , Wang Lin , Tang Xu , Zhang Renhe
Published: July 2023

China’s goal to achieve carbon (C) neutrality by 2060 requires scaling up photovoltaic (PV) and wind power from 1 to 10–15 PWh year−1(refs. 1–5). Following the historical rates of renewable installation1, a recent high-resolution energy-system model6and forecasts based on China’s 14th Five-year Energy Development (CFED)7, however, only indicate that the capacity will reach 5–9.5 PWh year−1by 2060. Here we show that, by individually optimizing the deployment of 3,844 new utility-scale PV and wind power plants coordinated with ultra-high-voltage (UHV) transmission and energy storage and accounting for power-load flexibility and learning dynamics, the capacity of PV and wind power can be increased from 9 PWh year−1(corresponding to the CFED path) to 15 PWh year−1, accompanied by a reduction in the average abatement cost from US$97 to US$6 per tonne of carbon dioxide (tCO2). To achieve this, annualized investment in PV and wind power should ramp up from US$77 billion in 2020 (current level) to US$127 billion in the 2020s and further to US$426 billion year−1in the 2050s. The large-scale deployment of PV and wind power increases income for residents in the poorest regions as co-benefits. Our results highlight the importance of upgrading power systems by building energy storage, expanding transmission capacity and adjusting power load at the demand side to reduce the economic cost of deploying PV and wind power to achieve carbon neutrality in China.
Evolutionary histories of breast cancer and related clones
Authors: Nishimura Tomomi , Kakiuchi Nobuyuki , Yoshida Kenichi , Sakurai Takaki , Kataoka Tatsuki R. , Kondoh Eiji , Chigusa Yoshitsugu , Kawai Masahiko , Sawada Morio , Inoue Takuya , Takeuchi Yasuhide , Maeda Hirona , Baba Satoko , Shiozawa Yusuke , Saiki Ryunosuke , Nakagawa Masahiro M. , Nannya Yasuhito , Ochi Yotaro , Hirano Tomonori , Nakagawa Tomoe , Inagaki-Kawata Yukiko , Aoki Kosuke , Hirata Masahiro , Nanki Kosaku , Matano Mami , Saito Megumu , Suzuki Eiji , Takada Masahiro , Kawashima Masahiro , Kawaguchi Kosuke , Chiba Kenichi , Shiraishi Yuichi , Takita Junko , Miyano Satoru , Mandai Masaki , Sato Toshiro , Takeuchi Kengo , Haga Hironori , Toi Masakazu , Ogawa Seishi
Published: July 2023

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1–3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.
A transfer learning-based multimodal neural network combining metadata and multiple medical images for glaucoma type diagnosis
Authors: Li Yi , Han Yujie , Li Zihan , Zhong Yi , Guo Zhifen
Published: July 2023

Glaucoma is an acquired optic neuropathy, which can lead to irreversible vision loss. Deep learning(DL), especially convolutional neural networks(CNN), has achieved considerable success in the field of medical image recognition due to the availability of large-scale annotated datasets and CNNs. However, obtaining fully annotated datasets like ImageNet in the medical field is still a challenge. Meanwhile, single-modal approaches remain both unreliable and inaccurate due to the diversity of glaucoma disease types and the complexity of symptoms. In this paper, a new multimodal dataset for glaucoma is constructed and a new multimodal neural network for glaucoma diagnosis and classification (GMNNnet) is proposed aiming to address both of these issues. Specifically, the dataset includes the five most important types of glaucoma labels, electronic medical records and four kinds of high-resolution medical images. The structure of GMNNnet consists of three branches. Branch 1 consisting of convolutional, cyclic and transposition layers processes patient metadata, branch 2 uses Unet to extract features from glaucoma segmentation based on domain knowledge, and branch 3 uses ResFormer to directly process glaucoma medical images.Branch one and branch two are mixed together and then processed by the Catboost classifier. We introduce a gradient-weighted class activation mapping (Grad-GAM) method to increase the interpretability of the model and a transfer learning method for the case of insufficient training data,i.e.,fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. The results show that GMNNnet can better present the high-dimensional information of glaucoma and achieves excellent performance under multimodal data.
The difference between ‘placebo group’ and ‘placebo control’: a case study in psychedelic microdosing
Authors: Szigeti Balázs , Nutt David , Carhart-Harris Robin , Erritzoe David
Published: July 2023

In medical trials, ‘blinding’ ensures the equal distribution of expectancy effects between treatment arms in theory; however, blinding often fails in practice. We use computational modelling to show how weak blinding, combined with positive treatment expectancy, can lead to an uneven distribution of expectancy effects. We call this ‘activated expectancy bias’ (AEB) and show that AEB can inflate estimates of treatment effects and create false positive findings. To counteract AEB, we introduce theCorrect Guess Rate Curve (CGRC), a statistical tool that can estimate the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. To demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed the ‘self-blinding psychedelic microdose trial’ dataset. Results suggest that observed placebo-microdose differences are susceptible to AEB and are at risk of being false positive findings, hence, we argue that microdosing can be understood as active placebo. These results highlight the important difference between ‘trials with a placebo-control group’, i.e., when a placebo control group is formally present, and ‘placebo-controlled trials’, where patients are genuinely blind. We also present a new blinding integrity assessment tool that is compatible with CGRC and recommend its adoption.
Assessment of groundwater hydrochemistry, water quality, and health risk in Hainan Island, China
Authors: Hou Qingqin , Pan Yujie , Zeng Min , Wang Simiao , Shi Huanhuan , Huang Changsheng , Peng Hongxia
Published: July 2023

Groundwater is an important source of water for human sustenance. The determination of groundwater quality at island sites is an urgent priority in China, but there are lacking systematic reports relating to them. Here, 63 groups of groundwater samples were collected and analyzed of Hainan Island. The groundwater in the study area is weakly alkaline, mainly comprising hard and soft freshwater. The predominant anions and cations are HCO3−, and Ca2+ and Na+, respectively, and the main water chemistry types are HCO3–Cl–Na and HCO3–Cl–Na–Ca. The chemical evolution of groundwater is mainly affected by water–rock interactions, cation exchange, and human activity. The groundwater is mostly of high quality and, in most areas, is suitable for drinking and irrigation. Contrastingly, the water quality in the west of the island is relatively poor. The spatial distribution of the risk coefficient (HQ) is consistent with the spatial variation in the NO3− concentrations in the groundwater. Notably, there are unacceptable health risks for different groups of people, with infants having the greatest level of impact, followed by children, teenagers, and adults. This study provides a valuable reference for the development and utilization of groundwater resources, as well as the improvement of aquatic ecological conditions on Hainan Island and other island areas worldwide.
Development of quantitative multiplex RT-qPCR one step assay for detection of hepatitis delta virus
Authors: da Silva Queiroz Jackson Alves , Roca Tárcio Peixoto , Souza Rutilene Barbosa , de Souza Luiz Fellype Alves , Passos-Silva Ana Maísa , da Silva André Luiz Ferreira , de Castro e Silva Eugênia , Borzacov Lourdes Maria Pinheiro , de Cássia Pontello Rampazzo Rita , dos Santos Pereira Soraya , Dantas Thor Oliveira , Mazaro Janaína , Villar Lívia Melo , Salcedo Juan Miguel Villalobos , da Matta Daniel Archimedes , Vieira Deusilene
Published: July 2023

Hepatitis Delta is a disease caused by exposure to hepatitis B (HBV) and hepatitis D (HDV) viruses, usually with a more severe clinical outcome when compared to an HBV monoinfection. To date, the real prevalence of HDV infection is underestimated and detection methods are poorly available, especially in more endemic regions. Therefore, a one-step RT-qPCR method for quantification of HDV-RNA was developed. Biological samples were selected between 2017 and 2023 from patients at the Ambulatório Especializado em Hepatites Virais of the Centro de Pesquisa em Medicina Tropical de Rondônia and Serviço de Assistência Especializada and underwent the test developed by this study and a second quantitative RT-qPCR assay. The slope of the initial quantitative assay was − 3.321 with an efficiency of 100.04% and amplification factor equal to 2. Analysis of the repeatability data revealed a Limit of Quantification of 5 copies/reaction and Limit of Detection (95%) of 2.83 copies per reaction. In the diagnostic sensitivity tests, there was an accuracy of 97.37% when compared to the reference test. This assay proved to be highly efficient and reproducible, making it a valuable tool to monitor hepatitis Delta patients and assess the risk of disease progression, as well as the effectiveness of treatment.
Disease burden of congenital Zika virus syndrome in Brazil and its association with socioeconomic data
Authors: de Amorin Vilharba Bruna Luiza , Yamamura Mellina , de Azevedo Micael Viana , Fernandes Wagner de Souza , Santos-Pinto Cláudia Du Bocage , de Oliveira Everton Falcão
Published: July 2023

Zika virus (ZIKV) infection became a global public health concern, causing an epidemic in Latin America from 2015 to 2016, when a sudden increase in cases of microcephaly and other congenital anomalies was observed. In 2016, the Centers for Disease Control and Prevention and the World Health Organization defined congenital Zika-associated syndrome (CZS) as a set of congenital anomalies seen in children born to mothers with a history of gestational Zika fever, who have microcephaly as the most prevalent clinical sign. In order to describe the magnitude of CZS in Brazil, this study estimated the burden of disease due to CZS in Brazil using the disability-adjusted life years (DALY) indicator and other frequency measures, such as incidence and mortality rate, during the years 2015–2020. The association of these indicators with socioeconomic variables was also evaluated using Spearman's correlation coefficient. Choropleth maps were used to evaluate the spatial distribution of the indicators evaluated and the spatial autocorrelation was verified by the Bivariate Moran Local Index. From 2015 to 2020, 3,591 cases of CZS were confirmed in Brazil, with an incidence of 44.03 cases per 1000 live births, and a specific mortality of 12.35 deaths per 1000 live births. A global loss of 30,027.44 DALYs was estimated from 2015 to 2020. The Northeast region had the highest values for all health indicators assessed. Spatial correlation and autocorrelation analyses showed significant associations between health and socioeconomic indicators, such as per capita income, Gini index, illiteracy rate and basic sanitation. The study allowed us to have access to all reported cases of CZS, showing us the possible situation of the disease in Brazil; therefore, we believe that our results can help in the understanding of future studies.
Catalytic dechlorination of 1,2-DCA in nano Cu0-borohydride system: effects of Cu0/Cun+ ratio, surface poisoning, and regeneration of Cu0 sites
Authors: Boparai Hardiljeet Kaur , El-Sharnouby Omneya , O’Carroll Denis M.
Published: July 2023

Aqueous-phase catalyzed reduction of organic contaminants via zerovalent copper nanoparticles (nCu0), coupled with borohydride (hydrogen donor), has shown promising results. So far, the research on nCu0 as a remedial treatment has focused mainly on contaminant removal efficiencies and degradation mechanisms. Our study has examined the effects of Cu0/Cun+ ratio, surface poisoning (presence of chloride, sulfides, humic acid (HA)), and regeneration of Cu0 sites on catalytic dechlorination of aqueous-phase 1,2-dichloroethane (1,2-DCA) via nCu0-borohydride. Scanning electron microscopy confirmed the nano size and quasi-spherical shape of nCu0 particles. X-ray diffraction confirmed the presence of Cu0 and Cu2O and x-ray photoelectron spectroscopy also provided the Cu0/Cun+ ratios. Reactivity experiments showed that nCu0 was incapable of utilizing H2 from borohydride left over during nCu0 synthesis and, hence, additional borohydride was essential for 1,2-DCA dechlorination. Washing the nCu0 particles improved their Cu0/Cun+ ratio (1.27) and 92% 1,2-DCA was removed in 7 h with kobs = 0.345 h−1 as compared to only 44% by unwashed nCu0 (0.158 h−1) with Cu0/Cun+ ratio of 0.59, in the presence of borohydride. The presence of chloride (1000–2000 mg L−1), sulfides (0.4–4 mg L−1), and HA (10–30 mg L−1) suppressed 1,2-DCA dechlorination; which was improved by additional borohydride probably via regeneration of Cu0 sites. Coating the particles decreased their catalytic dechlorination efficiency. 85–90% of the removed 1,2-DCA was recovered as chloride. Chloroethane and ethane were main dechlorination products indicating hydrogenolysis as the major pathway. Our results imply that synthesis parameters and groundwater solutes control nCu0 catalytic activity by altering its physico-chemical properties. Thus, these factors should be considered to develop an efficient remedial design for practical applications of nCu0-borohydride.
Priming of Citrullus lanatus var. Colocynthoides seeds in seaweed extract improved seed germination, plant growth and performance under salinity conditions
Authors: Radwan Asmaa M. , Ahmed Entesar A. , Donia Abdelraheim M. , Mustafa Abeer E. , Balah Mohamed A.
Published: July 2023

Citrullus lanatus var. Colocynthoide “Gurum” is an unconventional crop that can be utilized as a new source of edible oil and has the ability to grow in a variety of harsh conditions. To mitigate the adverse effects of salinity on seed germination and plant performance of C. lanatus, seeds were primed in the aqueous extracts of the seaweed Ulva lactuca before planting under greenhouse conditions. The aqueous extract of U. lactuca at 8% w/v led to maximal seed germination percentage and seedling growth of C. lanatus. Moreover, U. lactuca extract counteracted the negative effects of salt stress on the plant by significantly increasing the activity of SOD, CAT, and POD. The bioactive components of U. lactuca, e.g. glycine betaine and phenolic compounds can account for such beneficial role of algal extract on C. lanatus. Thus, priming of C. lanatus seeds in U. lactuca extract with various concentrations of U. lactuca extract can be employed as an effective practice for successful seed germination, improved plant growth and enhanced salt resistance, probably as a result of increased antioxidant enzymes activity and photosynthetic pigments.
Potential biomarkers for southern African hunter-gatherer arrow poisons applied to ethno-historical and archaeological samples
Authors: Isaksson Sven , Högberg Anders , Lombard Marlize , Bradfield Justin
Published: July 2023

The detection of complex poison recipes applied to ancient hunting weapons has the potential to provide important insights into traditional pharmacological knowledge systems. Yet, recipes comprising many ingredients can be challenging to decipher, especially in older samples that have undergone biodegradation. We present the results of our attempt to analyze samples of poison collected from nineteenth and twentieth century arrowheads from southern Africa, and from a 1000-year-old archaeological bone point. The arrow poison residues and reference samples were analyzed by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR FTIR) and Gas Chromatography Mass Spectrometry (GC–MS). The ATR FTIR analysis is primarily able to separate between different arrow poison binder recipes. The extractives identified by GC–MS analysis consist of a multitude of components from both binders and active substances, confirming and adding to the results from the ATR FTIR analyses. We discuss the results in terms of potential biomarkers for arrow poisons in organic residue analyses of archaeological artefacts; that residues of toxic cardiotonic glycosides can be detected on curated and excavated arrow tips of between about 1000 and 100 years old, serves as proof of concept for working with older materials in the future.
A novel, low-cost microfluidic device with an integrated filter for rapid, ultrasensitive, and high-throughput bioburden detection
Authors: Hasan Md. Sadique , Sundberg Chad , Tolosa Michael , Andar Abhay , Ge Xudong , Kostov Yordan , Rao Govind
Published: July 2023

Rapid and accurate bioburden detection has become increasingly necessary for food, health, pharmaceutical and environmental applications. To detect bioburden accurately, and in a highly sensitive manner, we have fabricated a novel microfluidic device with an integrated filter to trap the cells. Bioburden is detected on the filter paper in situ using the redox reaction of fluorescent label resorufin and a portable multichannel fluorometer is used for fluorescence measurement. The microfluidic device was fabricated in a facile, low-cost, and rapid way with microwave-induced thermally assisted bonding. To characterize the bonding quality of the microfluidic cassettes, different tests were performed, and the filter paper material and size were optimized. Primary Bacillus subtilis culture bacterial samples were filtered through the device to validate and investigate the performance parameters. Our results show that a limit of detection (LOD) of 0.037 CFU/mL can be achieved through this microfluidic device whereas the LOD in a normal microfluidic cassette in the fluorometer and the golden standard spectrophotometer are 0.378 and 0.128 CFU/mL respectively. The results depict that three to ten times LOD improvement is possible through this microfluidic cassette and more sensitive detection is possible depending on the volume filtered within a rapid 3 min. This novel microfluidic device along with the fluorometer can be used as a rapid portable tool for highly sensitive, accurate and high-throughput bacterial detection for different applications.
Perceived reward attainability may underlie dogs’ responses in inequity paradigms
Authors: McGetrick Jim , Peters Hugo , Korath Anna D. J. , Feitsch Romana , Siegmann Susanne , Range Friederike
Published: July 2023

Dogs have repeatedly been shown to give their paw to an experimenter more times for no reward when a rewarded conspecific partner is absent than when a rewarded conspecific is present, thereby showing inequity aversion. However, rather than being inequity averse, dogs might give their paw more when a partner is absent due to the experimenter’s procedure in which they move food in front of the subject to mimic feeding a partner. This action could increase subjects’ perception of reward attainability. We tested this hypothesis by introducing an improved type of control condition in which subjects were unrewarded for giving the paw in the presence of a rewarded box, a condition that more closely resembles the inequity condition. Inequity averse subjects’ performance did not differ based on whether the partner was another dog or a box. Moreover, these subjects gave the paw more times when no partner was present and the experimenter mimicked the feeding of a partner than when rewards were placed in the box. These results suggest that responses in the previous studies were inflated by subjects’ increased perception of reward attainability when no partner was present and, therefore, over-exaggerated dogs’ propensity to give up due to inequity aversion.