bluuebunny/crossref_metadata_2025 huggingface dataset:
A graph-based genome and pan-genome variation of the model plant Setaria
Authors: He Qiang , Tang Sha , Zhi Hui , Chen Jinfeng , Zhang Jun , Liang Hongkai , Alam Ornob , Li Hongbo , Zhang Hui , Xing Lihe , Li Xukai , Zhang Wei , Wang Hailong , Shi Junpeng , Du Huilong , Wu Hongpo , Wang Liwei , Yang Ping , Xing Lu , Yan Hongshan , Song Zhongqiang , Liu Jinrong , Wang Haigang , Tian Xiang , Qiao Zhijun , Feng Guojun , Guo Ruifeng , Zhu Wenjuan , Ren Yuemei , Hao Hongbo , Li Mingzhe , Zhang Aiying , Guo Erhu , Yan Feng , Li Qingquan , Liu Yanli , Tian Bohong , Zhao Xiaoqin , Jia Ruiling , Feng Baili , Zhang Jiewei , Wei Jianhua , Lai Jinsheng , Jia Guanqing , Purugganan Michael , Diao Xianmin
Published: June 2023

Setaria italica (foxtail millet), a founder crop of East Asian agriculture, is a model plant for C4 photosynthesis and developing approaches to adaptive breeding across multiple climates. Here we established the Setaria pan-genome by assembling 110 representative genomes from a worldwide collection. The pan-genome is composed of 73,528 gene families, of which 23.8%, 42.9%, 29.4% and 3.9% are core, soft core, dispensable and private genes, respectively; 202,884 nonredundant structural variants were also detected. The characterization of pan-genomic variants suggests their importance during foxtail millet domestication and improvement, as exemplified by the identification of the yield gene SiGW3, where a 366-bp presence/absence promoter variant accompanies gene expression variation. We developed a graph-based genome and performed large-scale genetic studies for 68 traits across 13 environments, identifying potential genes for millet improvement at different geographic sites. These can be used in marker-assisted breeding, genomic selection and genome editing to accelerate crop improvement under different climatic conditions.
Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials
Authors: Haney Margaret , Vallée Monique , Fabre Sandy , Collins Reed Stephanie , Zanese Marion , Campistron Ghislaine , Arout Caroline A. , Foltin Richard W. , Cooper Ziva D. , Kearney-Ramos Tonisha , Metna Mathilde , Justinova Zuzana , Schindler Charles , Hebert-Chatelain Etienne , Bellocchio Luigi , Cathala Adeline , Bari Andrea , Serrat Roman , Finlay David B. , Caraci Filippo , Redon Bastien , Martín-García Elena , Busquets-Garcia Arnau , Matias Isabelle , Levin Frances R. , Felpin François-Xavier , Simon Nicolas , Cota Daniela , Spampinato Umberto , Maldonado Rafael , Shaham Yavin , Glass Michelle , Thomsen Lars Lykke , Mengel Helle , Marsicano Giovanni , Monlezun Stéphanie , Revest Jean-Michel , Piazza Pier Vincenzo
Published: June 2023

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis’ positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.

ClinicalTrials.gov identifiers: NCT03325595, NCT03443895 and NCT03717272.
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study
Authors: Neul Jeffrey L. , Percy Alan K. , Benke Timothy A. , Berry-Kravis Elizabeth M. , Glaze Daniel G. , Marsh Eric D. , Lin Tim , Stankovic Serge , Bishop Kathie M. , Youakim James M.
Published: June 2023

Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine–proline–glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study (https://clinicaltrials.govidentifierNCT04181723), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks. For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was −4.9 versus −1.7 (P = 0.0175; Cohen’sdeffect size, 0.37), and LSM Clinical Global Impression–Improvement at week 12 was 3.5 versus 3.8 (P = 0.0030; effect size, 0.47). For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant–Toddler Checklist Social Composite score was −0.1 versus −1.1 (P = 0.0064; effect size, 0.43). Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity. Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.
Microcalcification crystallography as a potential marker of DCIS recurrence
Authors: Gosling Sarah B. , Arnold Emily L. , Davies Samantha K. , Cross Hannah , Bouybayoune Ihssane , Calabrese Doriana , Nallala Jayakrupakar , Pinder Sarah E. , Fu Liping , Lips Esther H. , King Lorraine , Marks Jeffrey , Hall Allison , Grimm Lars J. , Lynch Thomas , Pinto Donna , Stobart Hilary , Hwang E. Shelley , Wesseling Jelle , Geraki Kalotina , Stone Nicholas , Lyburn Iain D. , Greenwood Charlene , Rogers Keith D. ,   Grand Challenge PRECISION Consortium, Thompson Alastair , Nik-Zainal Serena , Sawyer Elinor J. , Davies Helen , Futreal Andrew , Navin Nicholas , Jonkers Jos , van Rheenen Jacco , Behbod Fariba , Schmidt Marjanka , Wessels Lodewyk F. A. , Rea Daniel , Bhattacharjee Proteeti , Collyar Deborah , Verschuur Ellen , van Oirsouw Marja
Published: June 2023

Ductal carcinoma in-situ (DCIS) accounts for 20–25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.
4-Methylumbelliferone enhances the effects of chemotherapy on both temozolomide-sensitive and resistant glioblastoma cells
Authors: Pibuel Matías A. , Poodts Daniela , Sias Sofía A. , Byrne Agustín , Hajos Silvia E. , Franco Paula G. , Lompardía Silvina L.
Published: June 2023

Glioblastoma (GBM) is the most frequent malignant primary tumor of the CNS in adults, with a median survival of 14.6 months after diagnosis. The effectiveness of GBM therapies remains poor, highlighting the need for new therapeutic alternatives. In this work, we evaluated the effect of 4-methylumbelliferone (4MU), a coumarin derivative without adverse effects reported, in combination with temozolomide (TMZ) or vincristine (VCR) on U251, LN229, U251-TMZ resistant (U251-R) and LN229-TMZ resistant (LN229-R) human GBM cells. We determined cell proliferation by BrdU incorporation, migration through wound healing assay, metabolic and MMP activity by XTT and zymography assays, respectively, and cell death by PI staining and flow cytometry. 4MU sensitizes GBM cell lines to the effect of TMZ and VCR and inhibits metabolic activity and cell proliferation on U251-R cells. Interestingly, the lowest doses of TMZ enhance U251-R and LN229-R cell proliferation, while 4MU reverts this and even sensitizes both cell lines to TMZ and VCR effects. We showed a marked antitumor effect of 4MU on GBM cells alone and in combination with chemotherapy and proved, for the first time, the effect of 4MU on TMZ-resistant models, demonstrating that 4MU would be a potential therapeutic alternative for improving GBM therapy even on TMZ-refractory patients.
Broad anti-pathogen potential of DEAD box RNA helicase eIF4A-targeting rocaglates
Authors: Obermann Wiebke , Azri Mohammad Farhan Darin , Konopka Leonie , Schmidt Nina , Magari Francesca , Sherman Julian , Silva Liliana M. R. , Hermosilla Carlos , Ludewig Andreas H. , Houhou Hicham , Haeberlein Simone , Luo Mona Yiting , Häcker Irina , Schetelig Marc F. , Grevelding Christoph G. , Schroeder Frank C. , Lau Gilbert Sei Kung , Taubert Anja , Rodriguez Ana , Heine Andreas , Yeo Tiong Chia , Grünweller Arnold , Taroncher-Oldenburg Gaspar
Published: June 2023

Inhibition of eukaryotic initiation factor 4A has been proposed as a strategy to fight pathogens. Rocaglates exhibit the highest specificities among eIF4A inhibitors, but their anti-pathogenic potential has not been comprehensively assessed across eukaryotes. In silico analysis of the substitution patterns of six eIF4A1 aa residues critical to rocaglate binding, uncovered 35 variants. Molecular docking of eIF4A:RNA:rocaglate complexes, and in vitro thermal shift assays with select recombinantly expressed eIF4A variants, revealed that sensitivity correlated with low inferred binding energies and high melting temperature shifts. In vitro testing with silvestrol validated predicted resistance in Caenorhabditiselegans and Leishmaniaamazonensis and predicted sensitivity in Aedes sp., Schistosomamansoni, Trypanosomabrucei, Plasmodiumfalciparum, and Toxoplasmagondii. Our analysis further revealed the possibility of targeting important insect, plant, animal, and human pathogens with rocaglates. Finally, our findings might help design novel synthetic rocaglate derivatives or alternative eIF4A inhibitors to fight pathogens.
Climate analogs can catalyze cross-regional dialogs for US specialty crop adaptation
Authors: Chaudhary Siddharth , Rajagopalan Kirti , Kruger Chad E. , Brady Michael P. , Fraisse Clyde W. , Gustafson David I , Hall Sonia A. , Hoogenboom Gerrit , Melnick Rachel L. , Reyes Julian , Stöckle Claudio O. , Sulser Timothy B.
Published: June 2023

Communication theory suggests that interactive dialog rather than information transmission is necessary for climate change action, especially for complex systems like agriculture. Climate analogs—locations whose current climate is similar to a target location’s future climate—have garnered recent interest as transmitting more relatable information; however, they have unexplored potential in facilitating meaningful dialogs, and whether the way the analogs are developed could make a difference. We developed climate context-specific analogs based on agriculturally-relevant climate metrics for US specialty crop production, and explored their potential for facilitating dialogs on climate adaptation options. Over 80% of US specialty crop counties had acceptable US analogs for the mid-twenty-first century, especially in the West and Northeast which had greater similarities in the crops produced across target-analog pairs. Western counties generally had analogs to the south, and those in other regions had them to the west. A pilot dialog of target-analog pairs showed promise in eliciting actionable adaptation insights, indicating potential value in incorporating analog-driven dialogs more broadly in climate change communication.
Explaining population booms and busts in Mid-Holocene Europe
Authors: Kondor Dániel , Bennett James S. , Gronenborn Detlef , Antunes Nicolas , Hoyer Daniel , Turchin Peter
Published: June 2023

Archaeological evidence suggests that the population dynamics of Mid-Holocene (Late Mesolithic to Initial Bronze Age, ca. 7000–3000 BCE) Europe are characterized by recurrent booms and busts of regional settlement and occupation density. These boom-bust patterns are documented in the temporal distribution of 14C dates and in archaeological settlement data from regional studies. We test two competing hypotheses attempting to explain these dynamics: climate forcing and social dynamics leading to inter-group conflict. Using the framework of spatially-explicit agent-based models, we translated these hypotheses into a suite of explicit computational models, derived quantitative predictions for population fluctuations, and compared these predictions to data. We demonstrate that climate variation during the European Mid-Holocene is unable to explain the quantitative features (average periodicities and amplitudes) of observed boom-bust dynamics. In contrast, scenarios with social dynamics encompassing density-dependent conflict produce population patterns with time scales and amplitudes similar to those observed in the data. These results suggest that social processes, including violent conflict, played a crucial role in the shaping of population dynamics of European Mid-Holocene societies.
Acute effects of transcranial direct current stimulation (tDCS) on peak torque and 5000 m running performance: a randomized controlled trial
Authors: dos Santos Leila Fernanda , dos Santos Silva Devisson , de Jesus Alves Micael Deivison , Moura Pereira Erika Vitoria , do Nascimento Hortência Reis , de Sousa Fernandes Matheus Santos , de Freitas Zanona Aristela , Knechtle Beat , Weiss Katja , Aidar Felipe J. , de Souza Raphael Fabricio
Published: June 2023

The benefits of transcranial direct current stimulation (tDCS) on brain function, cognitive response, and motor ability are well described in scientific literature. Nevertheless, the effects of tDCS on athletes’ performance remain unclear. To compare the acute effects of tDCS on the running performance of 5000 m (m) runners. Eighteen athletes were randomized into Anodal (n = 9) groups that received tDCS for 20 min and 2 mA, and Sham (n = 9), in the motor cortex region (M1). Running time in 5000 m, speed, perceived exertion (RPE), internal load and peak torque (Pt) were evaluated. The Shapiro–Wilk test followed by a paired Student’s t-test was used to compare Pt and total time to complete the run between the groups. The running time and speed of the Anodal group (p = 0.02; 95% CI 0.11–2.32; d = 1.24) was lower than the Sham group (p = 0.02, 95% CI 0.05–2.20; d = 1.15). However, no difference was found in Pt (p = 0.70; 95% CI − 0.75 to 1.11; d = 0.18), RPE (p = 0.23; 95% CI − 1.55 to 0.39; d = 0.60) and internal charge (p = 0.73; 95% CI − 0.77 to 1.09; d = 0.17). Our data indicate that tDCS can acutely optimize the time and speed of 5000 m runners. However, no alterations were found for Pt and RPE.
Early-life adversities and later-life reproductive patterns in women with fully traced reproductive history
Authors: Klimek Magdalena , Entringer Sonja , Matras Agnieszka , Blukacz Mateusz , Nenko Ilona , Galbarczyk Andrzej , Jasienska Grazyna
Published: June 2023

One of the most crucial determinants of early-life development is the experience of childhood adversities. However, limited evidence is available for how these experiences shape later-life reproductive outcomes in women. Here we test the association between early-life adversities and reproductive parameters in women. Post-reproductive women (N = 105; mean age = 59.7; SD = 10.09) were recruited at the Mogielica Human Ecology Study Site in Poland within a traditional population with a low prevalence of birth control usage and fully traced reproductive histories. Reproductive parameters, as well as exposure to early-life abuse and neglect, were assessed using questionnaires. Childhood adversity was associated negatively with age at menarche (p = 0.009). Analyses on specific subtypes revealed that compared to women who did not experience any kind of early-life adversities in childhood, those who were exposed to emotional (p = 0.007) and physical (p = 0.023) neglect had an earlier age at menarche, those who experienced emotional abuse reported an earlier age at first birth (p = 0.035), and those who were exposed to physical abuse gave birth to fewer number of sons (p = 0.010). Our results suggest that women exposed to childhood adversities experience earlier physiological reproductive readiness and timing of the first birth, but their overall biological condition might be impaired as they bear fewer sons.
The feasibility of enhanced pore space utilization in CO2 storage reservoirs using an artificially emplaced Si-gel flow barrier
Authors: Cossins Teya , Mishra Achyut , Haese Ralf R.
Published: June 2023

Carbon capture and storage is a key technology to abate CO2 emissions. One of the challenges towards ensuring the efficiency and the security of CO2 storage in reservoirs, such as open saline aquifers, is the low pore space utilization. This study investigates the feasibility of using an artificial Si-gel barrier to enhance pore space utilisation in such reservoirs under variable geological conditions. Conceptually, enhanced CO2 capillary trapping is achieved by emplacing a disk-shaped, low-permeability barrier above the CO2 injection point forcing the injected CO2 to migrate laterally underneath the barrier before transitioning to buoyancy-controlled migration. Multiphase fluid flow simulations were conducted to test the feasibility of this concept. Sensitivity analysis revealed that the barrier exhibits a strong control on CO2 plume geometry. Specifically, the relative impact of the barrier diameter on increasing the CO2 plume width, reducing the plume height and enhancing trapping varied between 67 and 86%. Capillary trapping was enhanced by 40–60% with a 20 m increase in barrier diameter in low permeability reservoirs. Additionally, the results indicate that the barrier can enhance the security of trapping CO2 in high permeability reservoirs. Results were tested for the South-West Hub reservoir, a case study area in Western Australia.
Assessment of goal-directed behavior and prospective memory in adult ADHD with an online 3D videogame simulating everyday tasks
Authors: Jylkkä Jussi , Ritakallio Liisa , Merzon Liya , Kangas Suvi , Kliegel Matthias , Zuber Sascha , Hering Alexandra , Laine Matti , Salmi Juha
Published: June 2023

The diagnosis of ADHD is based on real-life attentional-executive deficits, but they are harder to detect in adults than in children and objective quantitative measures reflecting these everyday problems are lacking. We developed an online version of EPELI 3D videogame for naturalistic and scalable assessment of goal-directed action and prospective memory in adult ADHD. In EPELI, participants perform instructed everyday chores in a virtual apartment from memory. Our pre-registered hypothesis predicted weaker EPELI performances in adult ADHD compared to controls. The sample comprised 112 adults with ADHD and 255 neurotypical controls comparable in age (mean 31, SD = 8 years), gender distribution (71% females) and educational level. Using web-browser, the participants performed EPELI and other cognitive tasks, including Conner’s Continuous Performance Test (CPT). They also filled out questionnaires probing everyday executive performance and kept a 5-day diary of everyday prospective memory errors. Self-reported strategy use in the EPELI game was also examined. The ADHD participants’ self-ratings indicated clearly more everyday executive problems than in the controls. Differences in the EPELI game were mostly seen in the ADHD participants’ higher rates of task-irrelevant actions. Gender differences and a group × gender interaction was found in the number of correctly performed tasks, indicating poorer performance particularly in ADHD males. Discriminant validity of EPELI was similar to CPT. Strategy use strongly predicted EPELI performance in both groups. The results demonstrate the feasibility of EPELI for online assessment and highlight the role of impulsivity as a distinctive everyday life problem in adult ADHD.
Spatial–temporal variation of extreme precipitation in the Yellow–Huai–Hai–Yangtze Basin of China
Authors: Wang Lichuan , Wang Jianhua , He Fan , Wang Qingming , Zhao Yong , Lu Peiyi , Huang Ya , Cui Hao , Deng Haodong , Jia Xinran
Published: June 2023

Climate warming leads to frequent extreme precipitation events, which is a prominent manifestation of the variation of the global water cycle. In this study, data from 1842 meteorological stations in the Huang–Huai–Hai–Yangtze River Basin and 7 climate models of CMIP6 were used to obtain the historical and future precipitation data using the Anusplin interpolation, BMA method, and a non-stationary deviation correction technique. The temporal and spatial variations of extreme precipitation in the four basins were analysed from 1960 to 2100. The correlation between extreme precipitation indices and their relationship with geographical factors was also analysed. The result of the study indicates that: (1) in the historical period, CDD and R99pTOT showed an upward trend, with growth rates of 14.14% and 4.78%, respectively. PRCPTOT showed a downward trend, with a decreasing rate of 9.72%. Other indices showed minimal change. (2) Based on SSP1-2.6, the intensity, frequency, and duration of extreme precipitation changed by approximately 5% at SSP3-7.0 and 10% at SSP5-8.5. The sensitivity to climate change was found to be highest in spring and autumn. The drought risk decreased, while the flood risk increased in spring. The drought risk increased in autumn and winter, and the flood risk increased in the alpine climate area of the plateau in summer. (3) Extreme precipitation index is significantly correlated with PRCPTOT in the future period. Different atmospheric circulation factors significantly affected different extreme precipitation indices of FMB. (4) CDD, CWD, R95pD, R99pD, and PRCPTOT are affected by latitude. On the other hand, RX1day and RX5day are affected by longitude. The extreme precipitation index is significantly correlated with geographical factors, and areas above 3000 m above sea level are more sensitive to climate change.
Buckling critical pressures in collapsible tubes relevant for biomedical flows
Authors: Laudato Marco , Mosca Roberto , Mihaescu Mihai
Published: June 2023

The behaviour of collapsed or stenotic vessels in the human body can be studied by means of simplified geometries like a collapsible tube. The objective of this work is to determine the value of the buckling critical pressure of a collapsible tube by employing Landau’s theory of phase transition. The methodology is based on the implementation of an experimentally validated 3D numerical model of a collapsible tube. The buckling critical pressure is estimated for different values of geometric parameters of the system by treating the relation between the intramural pressure and the area of the central cross-section as the order parameter function of the system. The results show the dependence of the buckling critical pressures on the geometric parameters of a collapsible tube. General non-dimensional equations for the buckling critical pressures are derived. The advantage of this method is that it does not require any geometric assumption, but it is solely based on the observation that the buckling of a collapsible tube can be treated as a second-order phase transition. The investigated geometric and elastic parameters are sensible for biomedical application, with particular interest to the study of the bronchial tree under pathophysiological conditions like asthma.
SelSA-1, a novel HDAC inhibitor demonstrates enhanced chemotherapeutic potential by redox modulation
Authors: Garg Ayushi , Desai Dhimant , Bhalla Aman , Thakur Shalu , Rastogi Pulkit , Kaushal Naveen
Published: June 2023

Colorectal cancer (CRC) is a multistep disorder resulting from genetic and epigenetic genome changes. It is the third most common malignancy in developed nations accounting for roughly 600,000 deaths annually. Persistent gut inflammation, as observed in inflammatory bowel disease (IBD), is a key risk factor for CRC development. From an epigenetic viewpoint, the pharmacological inhibition of HDACs using HDAC inhibitors such as SAHA has emerged as a suitable anticancer strategy in the recent past. However, the clinical success of these strategies is limited and has risk factors associated with their uses. Thus, considering the critical involvement of epigenetic regulation of key molecular mechanisms in carcinogenesis as well as HDAC inhibitory and anti-tumorigenic properties of Selenium (Se), we aimed to explore the potentially safer and enhanced chemotherapeutic potential of a Se derivative of SAHA namely SelSA-1, in an experimental model of colitis-associated experimental cancer (CAC) model and mechanism involved therein. The in vitro study indicated improved efficiency, specificity, and better safety margin in terms of lower IC50 value of SelSA-1 than SAHA in both NIH3T3 (9.44 and 10.87 µM) and HCT 115 (5.70 and 7.49 µM) cell lines as well on primary colonocytes (5.61 and 6.30 µM) respectively. In an in vivo experimental model, SelSA-1 efficiently demonstrated amelioration of the multiple plaque lesions (MPLs), tumor burden/incidence, and modulation of various histological and morphological parameters. Further, redox-mediated alterations in apoptotic mediators suggested induction of cancer cell apoptosis by SelSA-1. These findings indicate the enhanced chemotherapeutic and pro-resolution effects of SelSA-1 in part mediated through redox modulation of multiple epigenetic and apoptotic pathways.
A single-cell RNA-seq analysis unravels the heterogeneity of primary cultured human corneal endothelial cells
Authors: Català Pere , Groen Nathalie , LaPointe Vanessa L. S. , Dickman Mor M.
Published: June 2023

The cornea is a transparent and avascular tissue located in front of the eye. Its inner surface is lined by a monolayer of corneal endothelial cells (CECs), which maintain the cornea transparency. CECs remain arrested in a non-proliferative state and damage to these cells can compromise their function leading to corneal opacity. The primary culture of donor-derived CECs is a promising cell therapy. It confers the potential to treat multiple patients from a single donor, alleviating the global donor shortage. Nevertheless, this approach has limitations preventing its adoption, particularly culture protocols allow limited expansion of CECs and there is a lack of clear parameters to identify therapy-grade CECs. To address this limitation, a better understanding of the molecular changes arising from the primary culture of CECs is required. Using single-cell RNA sequencing on primary cultured CECs, we identify their variable transcriptomic fingerprint at the single cell level, provide a pseudo-temporal reconstruction of the changes arising from primary culture, and suggest markers to assess the quality of primary CEC cultures. This research depicts a deep transcriptomic understanding of the cellular heterogeneity arising from the primary expansion of CECs and sets the basis for further improvement of culture protocols and therapies.
Green preparation of graphene oxide nanosheets as adsorbent
Authors: Cao Kesheng , Tian Zhengshan , Zhang Xunyou , Wang Yabo , Zhu Qiuxiang
Published: June 2023

As a basic building block of graphene-based materials, graphene oxide (GO) plays an important role in scientific research and industrial applications. At present, numerous methods have been employed to synthesize GO, there are still some issues that need to be solved, thus it is of importance to develop a green, safe and low-cost GO preparation method. Herein, a green, safe and fast method was designed to prepare GO, namely, graphite powder was firstly oxidized in a dilute sulfuric acid solution (H2SO4, 6 mol/L) with hydrogen peroxide (H2O2, 30 wt%) as oxidant, and then exfoliated to GO by ultrasonic treatment in water. In this process, H2O2 was the only oxidant, and no other oxidants were used, thus the explosive nature of GO preparation reaction in the conventional methods could be completely eliminated. This method has other advantages such as green, fast, low-cost and no Mn-based residues. The experimental results confirm that obtained GO with oxygen-containing groups has better adsorption property compared to the graphite powder. As adsorbent, GO can remove methylene blue (50 mg/L) and Cd2+ (56.2 mg/L) from water with removal capacity of 23.8 mg/g and 24.7 mg/g, respectively. It provides a green, fast and low-cost method to prepare GO for some applications such as adsorbent.
acCRISPR: an activity-correction method for improving the accuracy of CRISPR screens
Authors: Ramesh Adithya , Trivedi Varun , Lee Sangcheon , Tafrishi Aida , Schwartz Cory , Mohseni Amirsadra , Li Mengwan , Lonardi Stefano , Wheeldon Ian
Published: June 2023

High throughput CRISPR screens are revolutionizing the way scientists unravel the genetic underpinnings of engineered and evolved phenotypes. One of the critical challenges in accurately assessing screening outcomes is accounting for the variability in sgRNA cutting efficiency. Poorly active guides targeting genes essential to screening conditions obscure the growth defects that are expected from disrupting them. Here, we develop acCRISPR, an end-to-end pipeline that identifies essential genes in pooled CRISPR screens using sgRNA read counts obtained from next-generation sequencing. acCRISPR uses experimentally determined cutting efficiencies for each guide in the library to provide an activity correction to the screening outcomes via calculation of an optimization metric, thus determining the fitness effect of disrupted genes. CRISPR-Cas9 and -Cas12a screens were carried out in the non-conventional oleaginous yeast Yarrowia lipolytica and acCRISPR was used to determine a high-confidence set of essential genes for growth under glucose, a common carbon source used for the industrial production of oleochemicals. acCRISPR was also used in screens quantifying relative cellular fitness under high salt conditions to identify genes that were related to salt tolerance. Collectively, this work presents an experimental-computational framework for CRISPR-based functional genomics studies that may be expanded to other non-conventional organisms of interest.
Crowded environments tune the fold-switching in metamorphic proteins
Authors: Zhang Ning , Guan Wenyan , Cui Shouqi , Ai Nana
Published: June 2023

Metamorphic proteins such as circadian clock protein KaiB and human chemokine XCL1 play vital roles in regulating biological processes, including gene expression, circadian clock and innate immune responses, and perform distinct functions in living cell by switching different structures in response to cellular environment stimuli. However, it is unclear how complex and crowded intracellular environments affect conformational rearrangement of metamorphic proteins. Here, the kinetics and thermodynamics of two well-characterized metamorphic proteins, circadian clock protein KaiB and human chemokine XCL1, were quantified in physiologically relevant environments by using NMR spectroscopy, indicating that crowded agents shift equilibrium towards the inactive form (ground-state KaiB and Ltn10-like state XCL1) without disturbing the corresponding structures, and crowded agents have predominantly impact on the exchange rate of XCL1 that switches folds on timescales of seconds, but have slightly impact on the exchange rate of KaiB that switches folds on timescales of hours. Our data shed light on how metamorphic proteins can respond immediately to the changed crowded intracellular conditions that induced by environmental cues and then execute different functions in living cell, and it also enhances our understanding of how environments enrich the sequence-structure-function paradigm.
Epidemic modelling of monitoring public behavior using surveys during pandemic-induced lockdowns
Authors: Koher Andreas , Jørgensen Frederik , Petersen Michael Bang , Lehmann Sune
Published: June 2023

Background

Implementing a lockdown for disease mitigation is a balancing act: Non-pharmaceutical interventions can reduce disease transmission significantly, but interventions also have considerable societal costs. Therefore, decision-makers need near real-time information to calibrate the level of restrictions.

Methods

We fielded daily surveys in Denmark during the second wave of the COVID-19 pandemic to monitor public response to the announced lockdown. A key question asked respondents to state their number of close contacts within the past 24 hours. Here, we establish a link between survey data, mobility data, and hospitalizations via epidemic modelling of a short time-interval around Denmark’s December 2020 lockdown. Using Bayesian analysis, we then evaluate the usefulness of survey responses as a tool to monitor the effects of lockdown and then compare the predictive performance to that of mobility data.

Results

We find that, unlike mobility, self-reported contacts decreased significantly in all regions before the nation-wide implementation of non-pharmaceutical interventions and improved predicting future hospitalizations compared to mobility data. A detailed analysis of contact types indicates that contact with friends and strangers outperforms contact with colleagues and family members (outside the household) on the same prediction task.

Conclusions

Representative surveys thus qualify as a reliable, non-privacy invasive monitoring tool to track the implementation of non-pharmaceutical interventions and study potential transmission paths.
Predicting microplastic masses in river networks with high spatial resolution at country level
Authors: Mennekes David , Nowack Bernd
Published: June 2023

Microplastics are a ubiquitous contaminant of natural waters, and a lot of field monitoring is currently performed. However, what is missing so far is a general understanding how emissions of microplastics are linked to environmental exposure, especially on larger geographic scales such as countries. Here we coupled a high-resolution microplastic release model with a fate model in rivers and lakes and parameterized it for Switzerland on a country scale to predict masses of microplastics in each river section for seven different polymers. The results show that catchment characteristics, for example, distribution of releases within the catchment, location and size of lakes or river connections, are as important as polymer properties such as density. There is no simple linear function of microplastic retention within a catchment in dependency of river length to the outlet. Instead, we found that different catchments cover a wide range of retained fractions for microplastics. Consequently, we argue that the availability and use of spatially distributed release data and performing modelling on high spatial resolution is of importance when estimating concentrations of microplastics in large areas such as countries.
1D aligned, n–p and n–n type ZnO heterojunction nanofibers for NO2 sensors: exploration of conduction mechanism using in situ impedance spectroscopy
Authors: Vishnuraj Ramakrishnan , Aleem Mahaboobbatcha , Nair Keerthi G , Pullithadathil Biji
Published: June 2023

1D aligned n–p type ZnO/Bi2O3 and n–n type ZnO/In2O3 heterojunction nanofibers have been developed via coaxial electrospinning approach and its complex sensing mechanisms have been deduced using in situ AC impedance spectroscopic studies.
Designing a nanothermometer using gel-to-liquid phase transition property of hybrid niosome
Authors: Lazarus Ronak , Kothari Rupal , Kaja Sravani , Venuganti Venkata Vamsi Krishna , Nag Amit
Published: June 2023

The gel-to-liquid reversible phase transition of a hybrid niosome is effectively utilized to design a nanothermometer for intracellular temperature sensing, by utilizing the fluorescence signal of a polarity-sensitive probe Coumarin 153.
Asymmetric [3+2]-cyclization of α-imino amide surrogates to construct 3,4-diaminopyrrolidine-2,5-diones
Authors: Ruan Peiran , Zhang Cefei , Wu Jin , Xiao Fengnan , Zhang Yongyan , Tan Qingfa , Su Zhishan , Feng Xiaoming , Liu Xiaohua
Published: June 2023

Using novel α-imino amide surrogates and chiral guanidine, diaminopyrrolidines derivatives could be obtained with good results and versatile application value. The role of guanidine was demonstrated by DFT calculations.
Not always an innocent bystander: the impact of stabilised phosphopantetheine moieties when studying nonribosomal peptide biosynthesis
Authors: Ho Y. T. Candace , Kaczmarski Joe A. , Tailhades Julien , Izoré Thierry , Steer David L. , Schittenhelm Ralf B. , Tosin Manuela , Jackson Colin J. , Cryle Max J.
Published: June 2023

Chemical stabilisation of carrier protein bound substrates in non-ribosomal peptide synthesis can result in a loss in activity of neighbouring catalytic domains.
Expedient (3+3)-annulation of in situ generated azaoxyallyl cations with diaziridines
Authors: Karjee Pallab , Mandal Santu , Debnath Bijoy , Namdev Nirali , Punniyamurthy Tharmalingam
Published: June 2023

A base-mediated (3+3)-annulation of diaziridines with in situ generated azaoxyallyl cations is described to produce 1,2,4-triazines under mild reaction conditions.
Correction: Molecular adduct of amantadine ferulate presents a pathway for slowing in vitro/vivo releases and raising synergistic antiviral effects via dual optimization salification strategy
Authors: Niu Yuan-Yuan , Wang Ling-Yang , Yu Yue-Ming , Li Yan-Tuan , Wu Zhi-Yong , Yan Cui-Wei
Published: June 2023

Correction for ‘Molecular adduct of amantadine ferulate presents a pathway for slowing in vitro/vivo releases and raising synergistic antiviral effects via dual optimization salification strategy’ by Yuan-Yuan Niu et al., CrystEngComm, 2021, 23, 4389–4401, https://doi.org/10.1039/D1CE00382H.
Degenerate and non-degenerate two-photon absorption of coumarin dyes
Authors: Elayan Ismael A. , Brown Alex
Published: June 2023

Two-photon absorption (2PA) spectroscopy is a robust bioimaging tool that depends on the determined cross-sections (σ2PA).
Structural and vibrational properties of wurtzite ZnO with oxygen-deficient defects: ab initio and potential-based calculations
Authors: Kislov Alexey N. , Zatsepin Anatoly F.
Published: June 2023

The structural and vibrational properties of the ZnO wurtzite phase with oxygen vacancies in different charged states are studied using first-principles and potential-based methods.
Transition from semiconductor to conductor of a Mg2N electride induced by strain
Authors: Wang Gui , Zhong Yongle , Xu Yiguo , Qian Zhengfang , Jiang Jingwen , Ma Zhuang
Published: June 2023

Mg2N electride has zero-dimension (0D) interstitial localized electrons and band structure with semiconductor properties, which transforms into metal when 2% stretch stress is applied to c-axis.
A combined inelastic neutron scattering and simulation study of the 3He@C60 endofullerene
Authors: Aouane Mohamed , Armstrong Jeff , Walkey Mark , Hoffman Gabriela , Bacanu George R. , Whitby Richard J. , Levitt Malcolm H. , Rols Stéphane
Published: June 2023

Uniting inelastic neutron scattering and numerical simulations to fully understand the dynamics of 3He atoms confined within C60 cages.
Conversion of carbon dioxide into solid carbon materials – a mini review
Authors: Cheng Xinlei , Wu Minxian , Li Jun , Wang Wenchang , Mitsuzaki Naotoshi , Chen Zhidong
Published: June 2023

Carbon dioxide reduction to carbon materials: a sustainable approach for mitigating emissions and producing valuable materials.
Interfacial electric field of BiVO4/WO3 photoanode-induced S-scheme charge transfer for enhanced photoelectrochemical performance
Authors: Zuo Jian , Guo Huili , Chen Shu , Pei Yong , Liu Canjun
Published: June 2023

A BiVO4/WO3 heterojunction photoanode with an internal electric field can induce a step-scheme charge transfer mechanism, which promotes the separation of photogenerated charge and reduces the applied bias voltage.
Development and pilot scale implementation of safe aerobic Cu/TEMPO oxidation in a batch reactor
Authors: Lemaitre Sylvain , Romain Anne-Lise , Bariere François , Craquelin Anthony , Copin Chloé , Jean Alexandre
Published: June 2023

A second generation process for the oxidation of benzylic alcohol 2, involved in the manufacture of Servier clinical candidateS44819, is described. This protocol was safely implemented at a kilogram scale and displays better sustainability compared to the original method.
Integrated electrosynthesis and biosynthesis for the production of adipic acid from lignin-derived phenols
Authors: Morejón Micjel Chávez , Franz Alexander , Karande Rohan , Harnisch Falk
Published: June 2023

We show that adipic acid (AA), a major building block for polyamides like Nylon-6,6, can be synthesized from lignin-derived feedstock by combining electrochemical hydrogenation with biotransformation.
Synthesis and application of polypyrrole nanofibers: a review
Authors: Liu Yang , Wu Feng
Published: June 2023

Polypyrrole nanofibers are generally synthesized by electrospinning, interfacial polymerization, and template methods, and show advanced functions and a broad range of applications in biomedical engineering, energy storage, and organic electronics.
Fully-unfused electron acceptors based on a steric boron dipyrromethene (BODIPY) core for organic solar cells
Authors: Xu Yuanyuan , Gao Xuyu , Song Xiaochen , You Duoquan , Wang Jingsheng , Wang Jian , Wu Yijing , Tao Xianwang , Ye Jian , Tao Youtian
Published: June 2023

Multi-functional steric BODIPY core was employed to improve light harvesting and modify intermolecular stacking for fully-unfused electron acceptors.
Cu9S5 and Cu9S5@UiO-66-NH2 composites exhibit excellent Fenton-like photocatalytic activities for the degradation of organic contaminants
Authors: Cheng Yong , Deng Lin , Wang Dan , Ji Changchun , Zhou Ying-Hua
Published: June 2023

Cu9S5 and Cu9S5@UiO-66-NH2 composites exhibited excellent Fenton-like photocatalytic activities for the degradation of organic contaminants.
Distinct fluorescence state, mechanofluorochromism of terpyridine conjugated fluorophores and the reusable sensing of nitroaromatics in aqueous medium
Authors: Sivadas Deepanjaly K. , Gayathri Parthasarathy , Ravi Sasikala , Karthikeyan Subramanian , Pannipara Mehboobali , Al-Sehemi Abdullah G. , Moon Dohyun , Anthony Savarimuthu Philip , Madhu Vedichi
Published: June 2023

Terpyridine derivatives showed charge transfer, locally excited and excimeric emission depending on the aromatic substituents, distinct mechanofluorochromism and reusable picric acid sensing.
Two-dimensional ReSe2 nanosheets as a high-performance photocatalyst
Authors: Pandey Anamika , Verma Ranjana , Srivastava Anchal
Published: June 2023

Two-dimensional rhenium diselenide transition metal dichalcogenide nanosheets are synthesized via a simple, environmentally benign hydrothermal approach, and act as a catalyst to degrade the pollutant rhodamine B under visible-light illumination.
Dual-functional organic surfactant for the effective stabilization of nano aluminium
Authors: Srinivas Billakanti , Prachuritha Bantumelli , Rao Vepa Kameswara , Muralidharan Krishnamurthi
Published: June 2023

An innovative approach that uses the dual functional capping agent 1-aminohexanol to stabilize aluminium nanoparticles (Nano-Al) produced via the colloidal synthesis process is reported.
Recyclable non-metal surface-enhanced Raman scattering substrate based on graphene oxide/ZIF-67 nanocomposites
Authors: Wang Shuang , Zhang Xiaoya , Xiang Qun , Zhou Sijie , Zheng Jun , Yan Ruiwen , Gao Guiqi
Published: June 2023

A highly SERS-active substrate of GO/ZIF-67 nanocomposites has been developed; owing to the exceptional thermal properties of GO, the GO/ZIF-67 nanocomposite can be reused several times.
Design and synthesis of self-assembled nonlinear optical multichromophore dendrimers with different acceptors
Authors: Li Zhibei , Luo Tongyu , Feng Shuhui , Ye Qi , Zheng Ziyun , Liang Huiyuan , Liu Jianhua , Liu Fenggang
Published: June 2023

Self-assembled three-arm multichromophore dendrimers H4 and H5 based on the same aniline donor and phenyl-trifluoromethyl-tricyanofuran (CF3-TCF) or perfluorophenyl-tricyanofuran (5F-TCF) acceptor with isophorone-derived bridges were developed.
Recent advances and perspectives of emerging two-dimensional transition metal carbide/nitride-based materials for organic pollutant photocatalysis
Authors: Jiang Zheng , Zhang Xinyue , Guo Sisheng , Zheng Yuqi , Wang Jian , Wen Tao , Wang Xiangke
Published: June 2023

This review outlines the fabrication strategies, morphological structures, electronic properties and applications of MXene based materials for photocatalysis in the treatment of recalcitrant organic pollutants (dyes, phenols, antibiotics and pharmaceuticals).
Electrochemical degradation of acrylic acid using Ti/Ta2O5–IrO2 electrode
Authors: Liu Jinrui , Meng Xiangxin , Zhai Luwei , Gao Guangfei , Jiang Wenqiang , Zhang Xuan
Published: June 2023

Acrylic acid was electrochemical degraded using Ti/Ta2O5–IrO2 electrode, which was characterized by SEM, XRD, CV, etc. The optimal degradation conditions were obtained by RSM. The degradation mechanism was investigated.
Designed synthesis of prussian blue@Cu-doped zinc phosphate nanocomposites for chemo/chemodynamic/photothermal combined cancer therapy
Authors: Hu Xiaoxue , Song Xiaoning , Yuan Yuan , Yao Xintao , Chen Xiangjun , Li Gang , Li Shengnan
Published: June 2023

PB@Cu2+/ZnP NPs with drug-loading property, photothermal effect, Fenton-like catalytic performance and high biosafety have been fabricated for synergistic chemo/chemodynamic/photothermal therapy.
Therapy and diagnosis of Alzheimer's disease: from discrete metal complexes to metal–organic frameworks
Authors: García-García Amalia , Rojas Sara , Rodríguez-Diéguez Antonio
Published: June 2023

Critical analysis of discrete metal compounds and metal–organic frameworks (MOFs) as a platform for the treatment and/or diagnosis of Alzheimer's disease.