bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface properties-dependent antifungal activity of silver nanoparticles
Authors: Matras Ewelina , Gorczyca Anna , Przemieniecki Sebastian Wojciech , Oćwieja Magdalena
Published: October 2022

Silver nanoparticles (AgNPs) exhibit unusual biocidal properties thanks to which they find a wide range of applications in diverse fields of science and industry. Numerous research studies have been devoted to the bactericidal properties of AgNPs while less attention has been focused on their fungicidal activity. Our studies were therefore oriented toward determining the impact of AgNPs characterized by different physicochemical properties on Fusarium avenaceum and Fusarium equiseti. The main hypothesis assumed that the fungicidal properties of AgNPs characterized by comparable morphology can be shaped by stabilizing agent molecules adsorbed on nanoparticle surfaces. Two types of AgNPs were prepared by the reduction of silver ions with sodium borohydride (SB) in the presence of trisodium citrate (TC) or cysteamine hydrochloride (CH). Both types of AgNPs exhibited a quasi-spherical shape. Citrate-stabilized AgNPs (TCSB-AgNPs) of an average size of 15 ± 4 nm were negatively charged. Smaller (12 ± 4 nm), cysteamine-capped AgNPs (CHSB-AgNPs) were characterized by a positive surface charge and higher silver ion release profile. The phytopathogens were exposed to the AgNPs in three doses equal to 2.5, 5 and 10 mg L−1 over 24 and 240 h. Additionally, the impact of silver ions delivered in the form of silver nitrate and the stabilizing agents of AgNPs on the fungi was also investigated. The response of phytopathogens to these treatments was evaluated by determining mycelial growth, sporulation and changes in the cell morphology. The results of our studies showed that CHSB-AgNPs, especially at a concentration of 10 mg L−1, strongly limited the vegetative mycelium growth of both species for short and long treatment times. The cell imaging revealed that CHSB-AgNPs damaged the conidia membranes and penetrated into the cells, while TCSB-AgNPs were deposited on their surface. The fungistatic (lethal) effect was demonstrated only for silver ions at the highest concentration for the F. equiseti species in the 240 h treatment. The number of spores of both Fusarium species was significantly reduced independently of the type of silver compounds used. Generally, it was found that the positively charged CHSB-AgNPs were more fungicidal than negatively charged TCSB-AgNPs. Thereby, it was established that the stabilizing agents of AgNPs and surface charge play a crucial role in the shaping of their fungicidal properties.
Actual conditions of person-to-object contact and a proposal for prevention measures during the COVID-19 pandemic
Authors: Hayashi Teruaki , Hase Daisuke , Suenaga Hikaru , Ohsawa Yukio
Published: October 2022

This study focused on human contact behavior with objects and discussed countermeasures during the COVID-19 pandemic across 15 location types. Reducing contact with objects and disinfecting items can be implemented at a relatively low cost. We created a protocol for organizing the objects, and 1260 subjects who went outside during a day between December 3–7, 2020 in Tokyo and Kanagawa, Japan were surveyed. The participants touched 7317 objects in total; the most common objects were doors, chairs, baskets, elevator equipment, and cash. One-way analysis of variance and Scheffé’s multiple comparison test showed that supermarkets had the lowest mean and median values despite having the highest number of users, contact objects, and object types. Conversely, the values for hotels were the highest, significantly higher than that for other places, excluding amusement parks, workplaces, and schools and universities. Furthermore, the long-tailed frequency distribution of the number of objects suggests that the objects touched by many individuals are limited; thus, it is important to determine the objects to be prioritized for disinfection at each location. The data and protocol could inform infection countermeasures that properly address the contact realities as they pertain to people’s behavior and objects.
A growth-based platform for detecting domain–peptide interactions in the cytoplasm of mammalian cells
Authors: Kimura Yosuke , Kashima Daiki , Kawahara Masahiro
Published: October 2022

Development of a method for detecting protein–protein interactions (PPIs) in living cells is important for therapeutic drug screening against various diseases including infectious diseases. We have recently developed a method named SOS localization-based interaction screening (SOLIS), in which we designed membrane-anchored and SOS-fused chimeric proteins, whose PPI-dependent association triggers membrane localization of the SOS-fused chimeric protein, activates the Ras/MAPK pathway, and induces cell growth. While SOLIS was able to detect relatively strong PPIs, further sensitivity was required for detecting intracellular endogenous PPIs typically having a micromolar order of dissociation constant (Kd). Here we develop high-sensitive SOLIS (H-SOLIS) that could universally detect PPIs with lower affinities. In order to improve the sensitivity, H-SOLIS introduces a heterodimeric helper interaction, in which addition of a small-molecule helper ligand could accommodate association of the two chimeric proteins and regulate the sensitivity. Four types of domain–peptide interactions having known Kd values are employed to examine the versatility and detection limit of H-SOLIS. Consequently, the heterodimer-inducible helper ligand dramatically enhances detection sensitivity, lowering the detection limit to a ten-micromolar order of Kd. Thus, H-SOLIS could be a platform to detect disease-related domain–peptide interactions for drug discovery screening.
Sensing nitriles with THz spectroscopy of urine vapours from cancers patients subject to chemotherapy
Authors: Vaks Vladimir , Anfertev Vladimir , Chernyaeva Maria , Domracheva Elena , Yablokov Anton , Maslennikova Anna , Zhelesnyak Alla , Baranov Alexei , Schevchenko Yuliia , Pereira Mauro Fernandes
Published: October 2022

A THz nonstationary high-resolution spectrometer based on semiconductor superlattice multipliers is applied to investigate the dynamics of urine composition for cancer patients treated with chemotherapy. The molecular urine composition of healthy volunteers and cancer patients was compared and contrasted. We have found a set of nitriles that either appeared after chemotherapy or increased in content, which are expected as a result of bio-chemical damage to the liver. While no damage can be detected at this stage by existing clinical methods, the identified nitriles are candidates for further large-scale systematic testing towards markers for nephrotoxicity of chemotherapy at an early stage of the treatment, when conventional diagnostics cannot identify substantial organ damage. Comparing the metabolite concentration dynamics with side effects during chemotherapy might then help individuate patients prone to severe complications and correct the treatment. Our devices are game-changers for THz spectroscopy of liquids: they allow spanning four different frequency ranges for a general evaluation of most substances found in the liquid and selecting a spectral interval that bypasses the strong absorption lines from substances such as water and ammonia, which may otherwise mask the detection of the target metabolites.
Pulse width and intensity effects of pulsed electric fields on cancerous and normal skin cells
Authors: Rao Xin , Chen Sophia , Alfadhl Yasir , Chen Xiaodong , Sun Lingling , Yu Liyang , Zhou Jun
Published: October 2022

Microsecond pulsed electric fields (PEF) have previously been used for various tumour therapies, such as gene therapy, electrochemotherapy and irreversible electroporation (IRE), due to its demonstrated ability. However, recently nanosecond pulsed electric fields (nsPEF) have also been used as a potential tumor therapy via inducing cell apoptosis or immunogenic cell death to prevent recurrence and metastasis by interacting with intracellular organelles. A large proportion of the existing in-vitro studies of nsPEF on cells also suggests cell necrosis and swelling/blebbing can be induced, but the replicability and potential for other effects on cells suggesting a complicated process which requires further investigation. Therefore, this study investigated the effects of pulse width and intensity of nsPEF on the murine melanoma cells (B16) and normal murine fibroblast cells (L929) through electromagnetic simulation and in-vitro experiments. Through examining the evolution patterns of potential difference and electric fields on the intracellular compartments, the simulation has shown a differential effect of nsPEF on normal and cancerous skin cells, which explains well the results observed in the reported experiments. In addition, the modelling has provided a clear evidence that a few hundreds of ns PEF may have caused a mixed mode of effects, i.e. a ‘cocktail effect’, including cell electroporation and IRE due to an over their threshold voltage induced on the plasma membrane, as well as cell apoptosis and other biological effects caused by its interaction with the intracellular compartments. The in-vitro experiments in the pulse range of the hundreds of nanoseconds showed a possible differential cytotoxicity threshold of electric field intensity between B16 cells and L929 cells.
Data augmentation with improved regularisation and sampling for imbalanced blood cell image classification
Authors: Rana Priyanka , Sowmya Arcot , Meijering Erik , Song Yang
Published: October 2022

Due to progression in cell-cycle or duration of storage, classification of morphological changes in human blood cells is important for correct and effective clinical decisions. Automated classification systems help avoid subjective outcomes and are more efficient. Deep learning and more specifically Convolutional Neural Networks have achieved state-of-the-art performance on various biomedical image classification problems. However, real-world data often suffers from the data imbalance problem, owing to which the trained classifier is biased towards the majority classes and does not perform well on the minority classes. This study presents an imbalanced blood cells classification method that utilises Wasserstein divergence GAN, mixup and novel nonlinear mixup for data augmentation to achieve oversampling of the minority classes. We also present a minority class focussed sampling strategy, which allows effective representation of minority class samples produced by all three data augmentation techniques and contributes to the classification performance. The method was evaluated on two publicly available datasets of immortalised human T-lymphocyte cells and Red Blood Cells. Classification performance evaluated using F1-score shows that our proposed approach outperforms existing methods on the same datasets.
Comparison of definitions of bronchopulmonary dysplasia to reflect the long-term outcomes of extremely preterm infants
Authors: Jeon Ga Won , Oh Minkyung , Lee Juyoung , Jun Yong Hoon , Chang Yun Sil
Published: October 2022

Survivors of neonatal bronchopulmonary dysplasia (BPD) have persistent respiratory, neurodevelopmental, and growth impairment over the first few years of life and later childhood, which represents an emerging burden for health systems. Therefore, there is an increasing need for a new definition and grading system of BPD that predicts long-term outcomes of high-risk infants who need timely and proper intervention to improve outcomes. We compared new definitions of BPD (National Institute of Child Health and Human Development [NICHD] 2018 and Neonatal Research Network [NRN] 2019) to the original NICHD 2001 definition at 3 years of age using a nationwide cohort of extreme preterm infants. New definitions and severity grading were clearly related to respiratory, neurodevelopmental, and growth impairments at 3 years of age and at 18–24 months corrected age (CA), whereas the original NICHD 2001 definition was not. Furthermore, the negative effect of BPD on growth was ameliorated at 3 years of age compared to 18–24 months CA. However, the negative effect of BPD in neonates on the respiratory system and neurodevelopment persisted at 3 years of age. These new definitions should be adopted to identify high-risk infants and improve long-term outcomes by exact diagnosis and BPD severity classification.
Comparison between low, moderate, and high intensity aerobic training with equalized loads on biomarkers and performance in rats
Authors: de Carvalho Carlos Dellavechia , Valentim Rafael Rossi , Navegantes Luiz Carlos Carvalho , Papoti Marcelo
Published: October 2022

This study investigated the physiological and molecular responses of Wistar Hannover rats, submitted to three 5-week chronic training models, with similar training loads. Twenty-four Wistar Hanover rats were randomly divided into four groups: control (n = 6), low-intensity training (Z1; n = 6), moderate-intensity training (Z2; n = 6) and high-intensity training (Z3; n = 6). The three exercise groups performed a 5-week running training three times a week, with the same prescribed workload but the intensity and the volume were different between groups. An increase in maximal speed was observed after four weeks of training for the three groups that trained, with no difference between groups. Higher rest glycogen was also observed in the soleus muscle after training for the exercise groups compared to the control group. We also found that the Z2 group had a higher protein content of total and phosphorylated GSK3-β compared to the control group after five weeks of training. In conclusion, the present study shows that five weeks of treadmill training based on intensity zones 1, 2, and 3 improved performance and increased resting glycogen in the soleus muscle, therefore intensity modulation does not change the training program adaptation since the different program loads are equalized.
Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
Authors: Peduzzi Giulia , Archibugi Livia , Katzke Verena , Gentiluomo Manuel , Capurso Gabriele , Milanetto Anna Caterina , Gazouli Maria , Goetz Mara , Brenner Hermann , Vermeulen Roel C. H. , Talar-Wojnarowska Renata , Vanella Giuseppe , Tavano Francesca , Lucchesi Maurizio , Mohelnikova-Duchonova Beatrice , Chen Xuechen , Kiudelis Vytautas , Hegyi Péter , Oliverius Martin , Stocker Hannah , Stornello Caterina , Vodickova Ludmila , Souček Pavel , Neoptolemos John P. , Testoni Sabrina Gloria Giulia , Morelli Luca , Lawlor Rita T. , Basso Daniela , Izbicki Jakob R. , Ermini Stefano , Kupcinskas Juozas , Pezzilli Raffaele , Boggi Ugo , van Laarhoven Hanneke W. M. , Szentesi Andrea , Erőss Bálint , Capretti Giovanni , Schöttker Ben , Skieceviciene Jurgita , Aoki Mateus Nóbrega , van Eijck Casper H. J. , Cavestro Giulia Martina , Canzian Federico , Campa Daniele
Published: October 2022

The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10−5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
Aetiologies and clinical presentation of central nervous system infections in Vietnamese patients: a prospective study
Authors: Gabor Julian Justin , Anh Chu Xuan , Sy Bui Tien , Hoan Phan Quoc , Quyen Dao Thanh , The Nguyen Trong , Kuk Salih , Kremsner Peter G. , Meyer Christian G. , Song Le Huu , Velavan Thirumalaisamy P.
Published: October 2022

Knowledge of the clinical presentation of central nervous system (CNS) infections and the causative pathogens is crucial for appropriate diagnosis and rapid initiation of appropriate treatment to prevent severe neurological sequelae. The aim of this study is to understand the aetiology of CNS infections based on the clinical presentation of Vietnamese patients. A prospective hospital-based cohort study was conducted between May 2014 and May 2017. We screened 137 patients with clinically suspected CNS infection for fungal, bacterial and viral pathogens using their cerebrospinal fluid (CSF) and blood cultures. In addition, DNA or RNA extracted from CSF samples were subjected to nucleic acid testing (NAT) with a selective panel of bacterial, viral and fungal pathogens. At least one pathogen could be detected in 41% (n = 56) of the patients. The main pathogens causing CNS infections were Streptococcus suis (n = 16; 12%) and Neisseria meningitidis (n = 9; 7%), followed by Herpes simplex virus 1/2 (n = 4; 3%) and Klebsiella pneumoniae (n = 4; 3%). Other pathogens were only identified in a few cases. Patients with bacterial CNS infections were significantly older, had a worse outcome, a lower Glasgow Coma Scale (GCS), a higher rate of speech impairment and neck stiffness than patients with viral or tuberculous CNS infections. In northern Vietnam, adults are mostly affected by bacterial CNS infections, which have a severe clinical course and worse outcomes compared to viral or tuberculous CNS infections. Clinicians should be aware of the regional occurrence of pathogens to initiate rapid and appropriate diagnosis and treatment.
Development of lipid nanoparticles and liposomes reference materials (II): cytotoxic profiles
Authors: Syama Krishnapriya , Jakubek Zygmunt J. , Chen Sam , Zaifman Josh , Tam Yuen Yi C. , Zou Shan
Published: October 2022

Lipid based nanocarriers are one of the most effective drug delivery systems that is evident from the recent COVID-19 mRNA vaccines. The main objective of this study was to evaluate toxicity of six lipid based formulations with three surface charges—anionic, neutral or cationic, to establish certified reference materials (CRMs) for liposomes and siRNA loaded lipid nanoparticles (LNP-siRNA). Cytotoxicity was assessed by a proliferation assay in adherent and non-adherent cell lines. High concentration of three LNP-siRNAs did not affect viability of suspension cells and LNP-siRNAs were non-toxic to adherent cells at conventionally used concentration. Systematic evaluation using multiple vials and repeated test runs of three liposomes and three LNP-siRNA formulations showed no toxicity in HL60 and A549 cells up to 128 and 16 µg/mL, respectively. Extended treatment and low concentration of LNPs did not affect the viability of suspension cells and adherent cells at 96 h. Interestingly, 80% of A549 and HL60 cells in 3D conditions were viable when treated with cationic LNP-siRNA for 48 h. Taken together, anionic, cationic and neutral lipid formulations were non-toxic to cells and may be explored further in order to develop them as drug carriers.
Positive-electrode properties and crystal structures of Mg-rich transition metal oxides for magnesium rechargeable batteries
Authors: Kitamura Naoto , Konishi Yoichiro , Ma Wenli , Ishida Naoya , Mandai Toshihiko , Ishibashi Chiaki , Idemoto Yasushi
Published: October 2022

In this work, we focus on Mg–Fe–O and Mg–Ni–O with Mg-rich compositions as positive-electrode materials for magnesium rechargeable batteries, and prepare them by a thermal decomposition of precipitates obtained by a solution method. It is indicated from X-ray diffraction patterns that the Mg–Fe–O and Mg–Ni–O samples have the spinel and rocksalt structures, respectively. X-ray absorption near edge structures indicate that Fe and Ni are trivalent and divalent, respectively, in the Mg-rich oxides. From charge/discharge cycle test, it is demonstrated that the Mg–Fe–O shows higher discharge capacity than the other and then has good cycle performance while keeping a discharge capacity over 100 mA h g–1. To gain deeper understanding on a relationship between the electrode properties and the crystal structure of the Mg–Fe–O, the crystal structure is investigated by a Rietveld refinement using a synchrotron X-ray diffraction profile and an analysis on total correlation functions. It is indicated from these studies that a vacant octahedral site in the spinel structure is partially occupied by the excess Mg in the synthesized sample. This structural feature might result in a stable charge/discharge cycle performance of the Mg-rich Mg–Fe–O.
Subclinical diagnosis of cisplatin-induced ototoxicity with biomarkers
Authors: Generotti Charles , Cox Brandon C. , Singh Jarnail , Hamilton Deborah , McKenzie Erica , O’Malley Bert W. , Li Daqing
Published: October 2022

A mouse model with cisplatin-induced ototoxicity was used in addition to human samples from the ITMAT Biobank at the University of Pennsylvania. Mouse auditory brainstem responses (ABR), inner ear histology, perilymph cisplatin sampling, and measurement of serum prestin via ELISA were performed. Human serum prestin level was measured via ELISA in patients with otological issues after cisplatin treatment and compared to matched controls. Serum prestin was significantly elevated before ABR threshold shifts in mice exposed to cisplatin compared to control mice. Prestin concentration also correlated with the severity of hearing threshold shifts in mice. After an extended rest post-cisplatin treatment, prestin returned to baseline levels in mice and humans. Prestin was significantly elevated in the serum before the onset of objective hearing loss and correlated with the severity of hearing damage indicating that prestin may function as an effective biomarker of cisplatin-induced ototoxicity. Human serum prestin levels responded similarly to mice > 3 weeks from ototoxic exposure with decreased levels of prestin in the serum.
A new approach for incorporating sea-level rise in hybrid 2D/one-line shoreline models
Authors: Seenath Avidesh
Published: October 2022

Hybrid 2D/one-line shoreline models, which typically apply a finite volume approach to simulate sediment transport and the one-line theory to update the shoreline morphology, are being increasingly applied over meso timescales (101 to 102 years) to inform coastal management. The one-line theory assumption of a constant closure depth prevents these models from considering the effects of sea-level rise in the shoreline morphology update. Sea-level rise, an endogenous driving factor of meso timescale coastal behaviour, influences the closure depth through its effects on the wave climate. This paper presents a new hybrid 2D/one-line approach that enables a time-varying closure depth in response to annual variations in wave climate as a solution for mirroring the effects of sea-level rise on the coastal profile and associated shoreline evolution. This new hybrid approach is applied to hindcast meso timescale shoreline evolution in a sandy coastal system and compared against the traditional hybrid 2D/one-line approach. Results show that the traditional hybrid approach gives the most accurate predictions whereas the new hybrid approach overpredicts shoreline erosion. However, this overprediction is attributed to net closure depth overestimation. This attribution gives confidence that the shoreline response to the time-varying closure depth specified is within expectations since closure depth overestimation increases offshore sediment transport in shoreline models. Therefore, it is likely that enabling a time-varying closure depth in hybrid 2D/one-line models may improve meso timescale shoreline predictions under sea-level rise if closure depths can be accurately prescribed over time.
Effects of mesenchymal stem cells in renovascular disease of preclinical and clinical studies: a systematic review and meta-analysis
Authors: Wang Hong-Shen , Yi Ming-Yu , Wu Xi , Liu Qian , Deng Ying-Hao , Wu Ting , Wang Lin , Kang Yi-Xin , Luo Xiao-Qin , Yan Ping , Wang Mei , Duan Shao-Bin
Published: October 2022

Renal artery stenosis (RAS) causes severe renovascular hypertension, worsening kidney function, and increased cardiovascular morbidity. According to recent studies, mesenchymal stem cells (MSCs) administration is a promising therapy for the improvement of RAS outcomes. The meta-analysis aims to evaluate the therapeutic effects of MSC therapy on RAS. We performed a search in MEDLINE, Web of Science, Embase, and Cochrane Library from inception to 5, October 2022. We included 16 preclinical and 3 clinical studies in this meta-analysis. In preclinical studies, the pooled results indicated that animals treated with MSCs had lower levels of systolic blood pressure (SBP) (SMD = − 1.019, 95% CI − 1.434 to − 0.604, I2 = 37.2%, P = 0.000), serum creatinine (Scr) (SMD = − 1.112, 95% CI − 1.932 to − 0.293, I2 = 72.0%, P = 0.008), and plasma renin activity (PRA) (SMD = − 0.477, 95% CI − 0.913 to 0.042, I2 = 43.4%, P = 0.032). The studies also revealed increased levels of renal blood flow (RBF) in stenotic kidney (STK) (SMD = 0.774, 95% CI − 0.351 to 1.197, I2 = 0%, P = 0.000) and the glomerular filtration rate (GFR) of STK (SMD = 1.825, 95% CI 0.963 to 2.688, I2 = 72.6%, P = 0.000). In clinical studies, the cortical perfusion and fractional hypoxia of the contralateral kidney (CLK) were alleviated by MSC therapy. Taken together, this meta-analysis revealed that MSCs therapy might be a promising treatment for RAS. However, due to the discrepancy between preclinical studies and early clinical trials outcomes, MSC therapy couldn’t be recommended in clinical care for the moment, more high-quality randomized controlled clinical trials are needed to validate our conclusions and standardize MSCs protocols.
Relating individual cell division events to single-cell ERK and Akt activity time courses
Authors: Stern Alan D. , Smith Gregory R. , Santos Luis C. , Sarmah Deepraj , Zhang Xiang , Lu Xiaoming , Iuricich Federico , Pandey Gaurav , Iyengar Ravi , Birtwistle Marc R.
Published: October 2022

Biochemical correlates of stochastic single-cell fates have been elusive, even for the well-studied mammalian cell cycle. We monitored single-cell dynamics of the ERK and Akt pathways, critical cell cycle progression hubs and anti-cancer drug targets, and paired them to division events in the same single cells using the non-transformed MCF10A epithelial line. Following growth factor treatment, in cells that divide both ERK and Akt activities are significantly higher within the S-G2 time window (~ 8.5–40 h). Such differences were much smaller in the pre-S-phase, restriction point window which is traditionally associated with ERK and Akt activity dependence, suggesting unappreciated roles for ERK and Akt in S through G2. Simple metrics of central tendency in this time window are associated with subsequent cell division fates. ERK activity was more strongly associated with division fates than Akt activity, suggesting Akt activity dynamics may contribute less to the decision driving cell division in this context. We also find that ERK and Akt activities are less correlated with each other in cells that divide. Network reconstruction experiments demonstrated that this correlation behavior was likely not due to crosstalk, as ERK and Akt do not interact in this context, in contrast to other transformed cell types. Overall, our findings support roles for ERK and Akt activity throughout the cell cycle as opposed to just before the restriction point, and suggest ERK activity dynamics may be more important than Akt activity dynamics for driving cell division in this non-transformed context.
Exceptional preservation of internal organs in a new fossil species of freshwater shrimp (Caridea: Palaemonoidea) from the Eocene of Messel (Germany)
Authors: de Mazancourt Valentin , Wappler Torsten , Wedmann Sonja
Published: October 2022

A new species of extinct freshwater shrimp was discovered in the Eocene deposit of the Messel Pit Konservat-Lagerstätte. This rare find is represented by only a few specimens, one of which showing exceptionally preserved soft tissues and other internal parts like the stomach with possibly gastric ossicles in place, branchiae, the ovary, and the left mandible, never described in a fossil shrimp. The new species Bechleja brevirostris n. sp. is characterized by a short rostrum bearing 6–8 dorsal spines and one ventral tooth, and long second pereiopods with strong chelae. One additional specimen shows a slightly different morphology and might belong to a different species. The systematic position of the species among the superfamily Palaemonoidea is discussed, as well as implications for the knowledge of the paleoenvironment of Lake Messel and the paleobiogeography of the Eocene.
Evolution of naturally arising SARS-CoV-2 defective interfering particles
Authors: Girgis Samer , Xu Zaikun , Oikonomopoulos Spyros , Fedorova Alla D. , Tchesnokov Egor P. , Gordon Calvin J. , Schmeing T. Martin , Götte Matthias , Sonenberg Nahum , Baranov Pavel V. , Ragoussis Jiannis , Hobman Tom C. , Pelletier Jerry
Published: October 2022

Defective interfering (DI) particles arise during virus propagation, are conditional on parental virus for replication and packaging, and interfere with viral expansion. There is much interest in developing DIs as anti-viral agents. Here we characterize DI particles that arose following serial passaging of SARS-CoV-2 at high multiplicity of infection. The prominent DIs identified have lost ~84% of the SARS-CoV-2 genome and are capable of attenuating parental viral titers. Synthetic variants of the DI genomes also interfere with infection and can be used as conditional, gene delivery vehicles. In addition, the DI genomes encode an Nsp1-10 fusion protein capable of attenuating viral replication. These results identify naturally selected defective viral genomes that emerged and stably propagated in the presence of parental virus.
Fate mapping reveals mixed embryonic origin and unique developmental codes of mouse forebrain septal neurons
Authors: Magno Lorenza , Asgarian Zeinab , Apanaviciute Migle , Milner Yasmin , Bengoa-Vergniory Nora , Rubin Anna Noren , Kessaris Nicoletta
Published: October 2022

The septum is a key structure at the core of the forebrain that integrates inputs and relays information to other brain areas to support cognition and behaviours such as feeding and locomotion. Underlying these functions is a rich diversity of neuronal types and an intricate complexity of wiring across and within the septal region. We currently have very little understanding of how septal neuronal diversity emerges during development. Using transgenic mice expressing Cre in different subsets of telencephalic precursors we explored the origins of the three main neuronal types of the septal complex: GABAergic, cholinergic and glutamatergic neurons. We find that septal neurons originate from distinct neuroepithelial domains of the developing septum and are born at different embryonic time points. An exception to this is the GABAergic medial septal Parvalbumin-expressing population which is generated outside the septum from surrounding germinal zones. We identify the transcription factor BSX as being expressed in the developing glutamatergic neuron population. Embryonic elimination of BSX in the septum results in a reduction of septal glutamatergic cell numbers and a consequent deficit in locomotion. Further refinement of septal neuron diversity is needed to understand the multiple roles of septal neurons and their contribution to distinct behaviours.
Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis
Authors: Kaiser Marco S. , Milan Giulia , Ham Daniel J. , Lin Shuo , Oliveri Filippo , Chojnowska Kathrin , Tintignac Lionel A. , Mittal Nitish , Zimmerli Christian E. , Glass David J. , Zavolan Mihaela , Rüegg Markus A.
Published: October 2022

Muscle size is controlled by the PI3K-PKB/Akt-mTORC1-FoxO pathway, which integrates signals from growth factors, energy and amino acids to activate protein synthesis and inhibit protein breakdown. While mTORC1 activity is necessary for PKB/Akt-induced muscle hypertrophy, its constant activation alone induces muscle atrophy. Here we show that this paradox is based on mTORC1 activity promoting protein breakdown through the ubiquitin-proteasome system (UPS) by simultaneously inducing ubiquitin E3 ligase expression via feedback inhibition of PKB/Akt and proteasome biogenesis via Nuclear Factor Erythroid 2-Like 1 (Nrf1). Muscle growth was restored by reactivation of PKB/Akt, but not by Nrf1 knockdown, implicating ubiquitination as the limiting step. However, both PKB/Akt activation and proteasome depletion by Nrf1 knockdown led to an immediate disruption of proteome integrity with rapid accumulation of damaged material. These data highlight the physiological importance of mTORC1-mediated PKB/Akt inhibition and point to juxtaposed roles of the UPS in atrophy and proteome integrity.
Three-dimensional characterization of developing and adult ocular vasculature in mice using in toto clearing
Authors: Darche Marie , Verschueren Anna , Belle Morgane , Boucherit Leyna , Fouquet Stéphane , Sahel José Alain , Chédotal Alain , Cascone Ilaria , Paques Michel
Published: October 2022

The ocular vasculature is critically involved in many blinding diseases and is also a popular research model for the exploration of developmental and pathological angiogenesis. The development of ocular vessels is a complex, finely orchestrated sequence of events, involving spatial and temporal coordination of hyaloid, choroidal and retinal networks. Comprehensive studies of the tridimensional dynamics of microvascular remodeling are limited by the fact that preserving the spatial disposition of ocular vascular networks is cumbersome using classical histological procedures. Here, we demonstrate that light-sheet fluorescence microscopy (LFSM) of cleared mouse eyes followed by extensive virtual dissection offers a solution to this problem. To the best of our knowledge, this is the first 3D quantification of the evolution of the hyaloid vasculature and of post-occlusive venous remodeling together with the characterization of spatial distribution of various cell populations in ocular compartments, including the vitreous. These techniques will prove interesting to obtain other insights in scientific questions addressing organ-wide cell interactions.
An open-source molecular builder and free energy preparation workflow
Authors: Bieniek Mateusz K. , Cree Ben , Pirie Rachael , Horton Joshua T. , Tatum Natalie J. , Cole Daniel J.
Published: October 2022

Automated free energy calculations for the prediction of binding free energies of congeneric series of ligands to a protein target are growing in popularity, but building reliable initial binding poses for the ligands is challenging. Here, we introduce the open-source FEgrow workflow for building user-defined congeneric series of ligands in protein binding pockets for input to free energy calculations. For a given ligand core and receptor structure, FEgrow enumerates and optimises the bioactive conformations of the grown functional group(s), making use of hybrid machine learning/molecular mechanics potential energy functions where possible. Low energy structures are optionally scored using the gnina convolutional neural network scoring function, and output for more rigorous protein–ligand binding free energy predictions. We illustrate use of the workflow by building and scoring binding poses for ten congeneric series of ligands bound to targets from a standard, high quality dataset of protein–ligand complexes. Furthermore, we build a set of 13 inhibitors of the SARS-CoV-2 main protease from the literature, and use free energy calculations to retrospectively compute their relative binding free energies. FEgrow is freely available athttps://github.com/cole-group/FEgrow, along with a tutorial.
Artificial intelligence and machine learning in cancer imaging
Authors: Koh Dow-Mu , Papanikolaou Nickolas , Bick Ulrich , Illing Rowland , Kahn Charles E. , Kalpathi-Cramer Jayshree , Matos Celso , Martí-Bonmatí Luis , Miles Anne , Mun Seong Ki , Napel Sandy , Rockall Andrea , Sala Evis , Strickland Nicola , Prior Fred
Published: October 2022

An increasing array of tools is being developed using artificial intelligence (AI) and machine learning (ML) for cancer imaging. The development of an optimal tool requires multidisciplinary engagement to ensure that the appropriate use case is met, as well as to undertake robust development and testing prior to its adoption into healthcare systems. This multidisciplinary review highlights key developments in the field. We discuss the challenges and opportunities of AI and ML in cancer imaging; considerations for the development of algorithms into tools that can be widely used and disseminated; and the development of the ecosystem needed to promote growth of AI and ML in cancer imaging.
AC3-symmetric triple oxa[6]helicene with circularly polarized luminescence featuring parallel transition dipole moments
Authors: Liu Jun , Jiang Lihui , Chang Hao , Liu Haoliang , Cao Xiao-Yu , Zou Yingping , Hu Yunbin
Published: October 2022

The effect of molecular symmetry on CPL properties was first demonstrated in triple heterohelicenes by the newly synthesized triple oxa[6]helicene.
Sulfur-rich polymer nanoparticles prepared by miniemulsion polymerization
Authors: Uebel Fabian , Wei Wei , Remmers Moritz , Thérien-Aubin Héloïse
Published: October 2022

Sulfur was converted into sulfur-rich polymer nanoparticles using miniemulsion polymerization, resulting in improved conversion and processability compared to bulk polymerization.
Sensitive and multicolor detection of nitrite based on iodide-mediated etching of gold nanostars
Authors: Hong Chengyi , Li Dandan , Cao Siying , Huang Xin , Yang Hongfen , Yang Dan , Huang Zhiyong , Cai Ren , Tan Weihong
Published: October 2022

A colorimetric method was reported for the determination of nitrite with high selectivity and sensitivity based on iodide-mediated etching of gold nanostars.
ESIPT geometrical isomers with distinct mechanofluorochromism and intra/intermolecular H-bonding controlled tunable fluorescence
Authors: Gayathri Parthasarathy , Ravi Sasikala , Akshaya K. , Karthikeyan Subramanian , Pannipara Mehboobali , Al-Sehemi Abdullah G. , Moon Dohyun , Anthony Savarimuthu Philip
Published: October 2022

Geometrical isomerism and substituent variation in ESIPT fluorophores facilitated tunable fluorescence and contrasting stimuli-induced self-reversible fluorescence switching.
Two- and three-body fragmentation of multiply charged tribromomethane by ultrafast laser pulses
Authors: Bhattacharyya Surjendu , Borne Kurtis , Ziaee Farzaneh , Pathak Shashank , Wang Enliang , Venkatachalam Anbu Selvam , Marshall Nathan , Carnes Kevin D. , Fehrenbach Charles W. , Severt Travis , Ben-Itzhak Itzik , Rudenko Artem , Rolles Daniel
Published: October 2022

This article provides mechanistic insight into the two- and three-body fragmentation dynamics of CHBr3 after strong-field ionization and discusses the possible isomerization of CHBr3 to BrCHBr–Br (iso-CHBr3) prior to the fragmentation.
Understanding the influence of Bi/Sb substitution on carrier concentration in Mg3Sb2-based materials: decreasing bandgap enhances the degree of impurity ionization
Authors: Li Juan , Jia Fei , Han Kai , Sun Bing , Cao Lianzhen , Li Yingde , Zhang Shuai
Published: October 2022

The increased carrier concentration by Bi doping originates from the enhanced degree of donor impurity ionization in n-type Mg3Sb2-based materials.
Modulating the structure of iron-doped titanium nitride deposited on a nitrogen-doped carbon catalyst for the oxygen reduction reaction in Zn–air batteries
Authors: Zheng Pengfei , Hu Siqi , Han Lina , Fu Yidan , Zeng Xiaoyuan , Li Mian , Feng Jing , Sui Yudong , Dong Peng , Zhang Yingjie
Published: October 2022

The DFT calculations demonstrate that iron doping boosts the charge transfer rate of Ti0.95Fe0.05N/NC/C, reduces the thermodynamic energy barrier of OOH* formation, and thus enhances ORR catalytic activity.
Triggering favorable energy landscape: a general approach towards highly efficient and photostable organic solar cells
Authors: Zhang Kangning , Du Xiaoyan , Qiao Jiawei , Hu Haixia , Zhang Wenqing , Wang Linghua , Gao Mingsheng , Yin Hang , Qin Wei , Hao Xiaotao
Published: October 2022

A synergistic approach of interface modification and morphology control was utilized to trigger favorable energy landscape in the device level, which yields simultaneously improved efficiency and photostability in BTP-based organic solar cells.
Revealing superoxide-induced degradation in lead-free tin perovskite solar cells
Authors: Zhang Zhihao , Tian Xuesong , Wang Can , Jin Jialun , Jiang Yiting , Zhou Qin , Zhu Jingwei , Xu Jianbin , He Rui , Huang Yuanfang , Ren Shengqiang , Chen Cong , Gao Peng , Long Run , Zhao Dewei
Published: October 2022

Sn-based perovskite FASnI3 suffers more severe degradation under light/O2 than only O2 exposure, which is caused by the large amount of superoxide formation at numerous iodine vacancies through the reaction between O2 and photoexcited electrons.
Self-assembled glycyrrhetinic acid derivatives for functional applications: a review
Authors: Zou Linjun , Li Qinglong , Hou Yong , Chen Meiying , Xu Xudong , Wu Haifeng , Sun Zhaocui , Ma Guoxu
Published: October 2022

Glycyrrhetinic acid (GA), a famous natural product, has attracted much more attention because of its remarkable biological activity, natural sweetness, and good biocompatibility.
Sema4D–plexin-B1 signaling in recruiting dental stem cells for vascular stabilization on a microfluidic platform
Authors: Zhang Lili , Han Yuanyuan , Chen Qixin , Dissanayaka Waruna Lakmal
Published: October 2022

Sema4D promotes vascular stabilization by recruiting SHED through endothelial derived PDGF-BB.
Discovery of N-sulfonylated aminosalicylic acids as dual MCL-1/BCL-xL inhibitors
Authors: Chen Lijia , Chauhan Jay , Yap Jeremy L. , Goodis Christopher C. , Wilder Paul T. , Fletcher Steven
Published: October 2022

Deconstruction of a bicyclic tetrahydroquinoline-6-carboxylic acid scaffold into aminosalicylic acids yielded dual MCL-1/BCL-xL inhibitors from an MCL-1 selective lead.
Leaky membrane fusion: an ambivalent effect induced by antimicrobial polycations
Authors: Shi Shuai , Fan Helen , Hoernke Maria
Published: October 2022

With our strategy to identify easily overlooked leaky fusion induced by membrane-active antimicrobials, misinterpretation of membrane permeabilization is prevented.
Construction of high-performance triboelectric nanogenerators based on the microstructures of conical nanoneedles
Authors: Wang Lixia , Sun Xiang , Wang Dongfang , Wang Chen , Bi Zhaojie , Zhou Baokai , Zheng Lun , Niu Hongbin , Cui Pengyuan , Wang Jian , Li Qian
Published: October 2022

A triboelectric nanogenerator (TENG) based on a hot-embossed PHB membrane and ePTFE membrane displays excellent output performance.
A Brønsted acid-catalyzed thioacid addition toin situ-generated aldimine for the synthesis of isoindolinones with theN,S-acetal framework
Authors: Sadhu Milon M. , Khajuria Chhavi , Singh Vinod K.
Published: October 2022

A Brønsted acid catalyzed three-component reaction has been developed for the synthesis of isoindolinones containing N,S-acetal framework.
Scalable and sustainable production of Ti3C2Tz MXene and fluorine recovery from wastewater through cryolite precipitation
Authors: Carey Michael S. , Barsoum Michel W.
Published: October 2022

Treatment of HF or HCl/LiF etched Ti3C2Tz with 0.05 M NaHCO3 before water washing reduces the wastewater generated by 75%. Cryolite is precipated from the spent etching media.
Sustainable xanthophylls-containing poly(ε-caprolactone)s: synthesis, characterization, and use in green lubricants
Authors: Rodríguez-deLeón Eloy , Bah Moustapha , Báez José E. , Hernández-Sierra María T. , Moreno Karla J. , Nuñez-Vilchis Alejandro , Bonilla-Cruz José , Shea Kenneth J.
Published: October 2022

Sustainable polyesters initiators from renewable resources and additives in green lubricants.
Copper(ii) curcumin complexes for endoplasmic reticulum targeted photocytotoxicity
Authors: Banaspati Atrayee , Ramu Vanitha , Raza Md Kausar , Goswami Tridib K.
Published: October 2022

Cu(ii) curcumin complexes show significant photo-enhanced cytotoxicity in HeLa and A549 cancer cells in visible light via an apoptosis mechanism through generation of ROS with low dark toxicity.
Enhanced electrocaloric effect, energy storage density and pyroelectric response from a domain-engineered lead-free BaTi0.91Sn0.08Zr0.01O3 ferroelectric ceramic
Authors: Kacem Hend , Dhahri Ah. , Aouaini F. , Sassi Z. , Seveyrat L. , Lebrun L. , Dhahri J.
Published: October 2022

The temperature-dependent of (a) P–E hysteresis loops and (b) ΔT at different applied electric fields. (c) The pyroelectric energy harvesting density per cycle. (d) The relevant energy storage parameters of BTSZ ceramic as a function of temperature.
DFT investigation of the electronic and optical properties of hexagonal MX2/ZrXO (M = W, Mo and X = S, Se) van der Waals heterostructures for photovoltaic solar cell application
Authors: Sibhatu Aman kassaye , Teshome Tamiru , Akin-Ojo Omololu , Yimam Abubeker , Asres Georgies Alene
Published: October 2022

Using solar light we can directly generate renewable energies by using novel two-dimensional semiconductor materials. The green represents renewable energy, the grid part is a solar panel, and the two structures are semiconductor materials.
A crystal defect led zero thermal quenching β-NaYF4 : Eu3+,Dy3+ red emitting phosphor
Authors: Ling Shaokun , Chen Chang , Meng Kai , Yan Yifeng , Ming Junyun , Liao Sen , Huang Yingheng
Published: October 2022

VY vacancies make a predominant contribution to the zero thermal quenching property of β-NaYF4 : 0.065Eu3+,0.003Dy3+.
Influence of reactive oxygen species concentration and ambient temperature on the evolution of chemical bonds during plasma cleaning: a molecular dynamics simulation
Authors: Li Yuhai , Jiang Yilan , Liu Xujie , Bai Qingshun , Liu Hao , Wang Jingxuan , Zhang Peng , Lu Lihua , Yuan Xiaodong
Published: October 2022

The increased reaction species concentration and ambient temperature improved plasma cleaning ability
Evaluation of cytotoxic properties of two fluorescent fac-Re(CO)3 complexes bearing an N,N-bidentate benzimidazole coligand
Authors: Mansour Ahmed M. , Ibrahim Nourhan M. , Farag Ahmad M. , Abo-Elfadl Mahmoud T.
Published: October 2022

Tricarbonyl Re(i) complexes are piled in the intercellular junction and diffused inside the cells. This led to DNA fragmentations and both apoptotic and necrotic cell death.
Direct Michael addition/decarboxylation reaction catalyzed by a composite of copper ferrite nanoparticles immobilized on microcrystalline cellulose: an eco-friendly approach for constructing 3,4-dihydrocoumarin frameworks
Authors: Kumar Bhupender , Borah Biplob , Babu J. Nagendra , Chowhan L. Raju
Published: October 2022

Composites of copper ferrite oxide nanoparticles immobilized on microcrystalline cellulose were synthesized and studied for their catalytic activity toward the preparation of novel 3,4-dihydrocoumarin derivatives.
Facile synthesis of isoquinolines and isoquinolineN-oxidesviaa copper-catalyzed intramolecular cyclization in water
Authors: Zhang Lujun , Xiong Wenfang , Yao Biao , Liu Haitao , Li Meng , Qin Yu , Yu Yujian , Li Xu , Chen Meng , Wu Wanqing , Li Jianxiao , Wang Jinliang , Jiang Huanfeng
Published: October 2022

A facile copper-catalyzed intramolecular cyclization for the selective synthesis of isoquinolines and isoquinolineN-oxides in water is described.