bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of nonlinearity on Anderson localization of surface gravity waves
Authors: Ricard Guillaume , Novkoski Filip , Falcon Eric
Published: July 2024

Anderson localization is a multiple-scattering phenomenon of linear waves propagating within a disordered medium. Discovered in the late 50s for electrons, it has since been observed experimentally with cold atoms and with classical waves (optics, microwaves, and acoustics), but whether wave localization is enhanced or weakened for nonlinear waves is a long-standing debate. Here, we show that the nonlinearity strengthens the localization of surface-gravity waves propagating in a canal with a random bottom. We also show experimentally how the localization length depends on the nonlinearity, which has never been reported previously with any type of wave. To do so, we use a full space-and-time-resolved wavefield measurement as well as numerical simulations. The effects of the disorder level and the system’s finite size on localization are also reported. We also highlight the first experimental evidence of the macroscopic analog of Bloch’s dispersion relation of linear hydrodynamic surface waves over periodic bathymetry.
Automated single-cell proteomics providing sufficient proteome depth to study complex biology beyond cell type classifications
Authors: Ctortecka Claudia , Clark Natalie M. , Boyle Brian W. , Seth Anjali , Mani D. R. , Udeshi Namrata D. , Carr Steven A.
Published: July 2024

The recent technological and computational advances in mass spectrometry-based single-cell proteomics have pushed the boundaries of sensitivity and throughput. However, reproducible quantification of thousands of proteins within a single cell remains challenging. To address some of those limitations, we present a dedicated sample preparation chip, the proteoCHIP EVO 96 that directly interfaces with the Evosep One. This, in combination with the Bruker timsTOF demonstrates double the identifications without manual sample handling and the newest generation timsTOF Ultra identifies up to 4000 with an average of 3500 protein groups per single HEK-293T without a carrier or match-between runs. Our workflow spans 4 orders of magnitude, identifies over 50 E3 ubiquitin-protein ligases, and profiles key regulatory proteins upon small molecule stimulation. This study demonstrates that the proteoCHIP EVO 96-based sample preparation with the timsTOF Ultra provides sufficient proteome depth to study complex biology beyond cell-type classifications.
Shadows of quantum machine learning
Authors: Jerbi Sofiene , Gyurik Casper , Marshall Simon C. , Molteni Riccardo , Dunjko Vedran
Published: July 2024

Quantum machine learning is often highlighted as one of the most promising practical applications for which quantum computers could provide a computational advantage. However, a major obstacle to the widespread use of quantum machine learning models in practice is that these models, even once trained, still require access to a quantum computer in order to be evaluated on new data. To solve this issue, we introduce a class of quantum models where quantum resources are only required during training, while the deployment of the trained model is classical. Specifically, the training phase of our models ends with the generation of a ‘shadow model’ from which the classical deployment becomes possible. We prove that: (i) this class of models is universal for classically-deployed quantum machine learning; (ii) it does have restricted learning capacities compared to ‘fully quantum’ models, but nonetheless (iii) it achieves a provable learning advantage over fully classical learners, contingent on widely believed assumptions in complexity theory. These results provide compelling evidence that quantum machine learning can confer learning advantages across a substantially broader range of scenarios, where quantum computers are exclusively employed during the training phase. By enabling classical deployment, our approach facilitates the implementation of quantum machine learning models in various practical contexts.
Concentric hollow multi-hexagonal platelets from a small molecule
Authors: Liao Chenglong , Gong Yanjun , Che Yanxue , Ji Hongwei , Liu Bing , Zang Ling , Che Yanke , Zhao Jincai
Published: July 2024

The creation of well-defined hollow two-dimensional structures from small organic molecules, particularly those with controlled widths and numbers of segments, remains a formidable challenge. Here we report the fabrication of the well-defined concentric hollow two-dimensional platelets with programmable widths and numbers of segments through constructing a concentric multiblock two-dimensional precursor followed by post-processing. The fabrication of concentric multi-hexagons two-dimensional platelets is realized by the alternative heteroepitaxial growth of two donor-acceptor molecules. Upon ultraviolet irradiation, one of the two donor-acceptor molecules can be selectively oxidized by singlet oxygen generated during the process, and the oxidized product becomes more soluble due to increased polarity. This allows for selective removal of the oxidized segments simply by solvent dissolution, yielding hollow multiblock two-dimensional structures. The hollow two-dimensional platelets can be utilized as templates to lithograph complex electrodes with precisely controlled gap sizes, thereby offering a platform for examining the optoelectronic performance of functional materials.
The loci of environmental adaptation in a model eukaryote
Authors: Chen Piaopiao , Zhang Jianzhi
Published: July 2024

While the underlying genetic changes have been uncovered in some cases of adaptive evolution, the lack of a systematic study prevents a general understanding of the genomic basis of adaptation. For example, it is unclear whether protein-coding or noncoding mutations are more important to adaptive evolution and whether adaptations to different environments are brought by genetic changes distributed in diverse genes and biological processes or concentrated in a core set. We here perform laboratory evolution of 3360 Saccharomyces cerevisiae populations in 252 environments of varying levels of stress. We find the yeast adaptations to be primarily fueled by large-effect coding mutations overrepresented in a relatively small gene set, despite prevalent antagonistic pleiotropy across environments. Populations generally adapt faster in more stressful environments, partly because of greater benefits of the same mutations in more stressful environments. These and other findings from this model eukaryote help unravel the genomic principles of environmental adaptation.
Ultrastable and efficient slight-interlayer-displacement 2D Dion-Jacobson perovskite solar cells
Authors: Zhang Weichuan , Liu Ziyuan , Zhang Lizhi , Wang Hui , Jiang Chuanxiu , Wu Xianxin , Li Chuanyun , Yue Shengli , Yang Rongsheng , Zhang Hong , Zhang Jianqi , Liu Xinfeng , Zhang Yuan , Zhou Huiqiong
Published: July 2024

Stability has been a long-standing concern for solution-processed perovskite photovoltaics and their practical applications. However, stable perovskite materials for photovoltaic remain insufficient to date. Here we demonstrate a series of ultrastable Dion−Jacobson (DJ) perovskites (1,4-cyclohexanedimethanammonium)(methylammonium)n−1PbnI3n+1 (n ≥ 1) for photovoltaic applications. The scalable technology by blade-coated solar cells for the designed DJ perovskites (nominal n = 5) achieves a maximum stabilized power conversion efficiency (PCE) of 19.11% under an environmental atmosphere. Un-encapsulated cells by blade-coated technology retain 92% of their initial efficiencies for over 4000 hours under ~90% relative humidity (RH) aging conditions. More importantly, these cells also exhibit remarkable thermal (85 °C) and operational stability, which shows negligible efficiency loss after exceeding 5000-hour heat treatment or after operation at maximum power point (MPP) exceeding 6000 hours at 45 °C under a 100 mW cm−2 continuous light illumination.
General negative pressure annealing approach for creating ultra-high-loading single atom catalyst libraries
Authors: Wang Yi , Li Chongao , Han Xiao , Bai Jintao , Wang Xuejing , Zheng Lirong , Hong Chunxia , Li Zhijun , Bai Jinbo , Leng Kunyue , Lin Yue , Qu Yunteng
Published: July 2024

Catalyst systems populated by high-density single atoms are crucial for improving catalytic activity and selectivity, which can potentially maximize the industrial prospects of heterogeneous single-atom catalysts (SACs). However, achieving high-loading SACs with metal contents above 10 wt% remains challenging. Here we describe a general negative pressure annealing strategy to fabricate ultrahigh-loading SACs with metal contents up to 27.3–44.8 wt% for 13 different metals on a typical carbon nitride matrix. Furthermore, our approach enables the synthesis of high-entropy single-atom catalysts (HESACs) that exhibit the coexistence of multiple metal single atoms with high metal contents. In-situ aberration-corrected HAADF-STEM (AC-STEM) combined with ex-situ X-ray absorption fine structure (XAFS) demonstrate that the negative pressure annealing treatment accelerates the removal of anionic ligand in metal precursors and boosts the bonding of metal species with N defective sites, enabling the formation of dense N-coordinated metal sites. Increasing metal loading on a platinum (Pt) SAC to 41.8 wt% significantly enhances the activity of propane oxidation towards liquid products, including acetone, methanol, and acetic acid et al. This work presents a straightforward and universal approach for achieving many low-cost and high-density SACs for efficient catalytic transformations.
SPRING licenses S1P-mediated cleavage of SREBP2 by displacing an inhibitory pro-domain
Authors: Hendrix Sebastian , Dartigue Vincent , Hall Hailee , Bawaria Shrankhla , Kingma Jenina , Bajaj Bilkish , Zelcer Noam , Kober Daniel L.
Published: July 2024

Site-one protease (S1P) conducts the first of two cleavage events in the Golgi to activate Sterol regulatory element binding proteins (SREBPs) and upregulate lipogenic transcription. S1P is also required for a wide array of additional signaling pathways. A zymogen serine protease, S1P matures through autoproteolysis of two pro-domains, with one cleavage event in the endoplasmic reticulum (ER) and the other in the Golgi. We recently identified the SREBP regulating gene, (SPRING), which enhances S1P maturation and is necessary for SREBP signaling. Here, we report the cryo-EM structures of S1P and S1P-SPRING at sub-2.5 Å resolution. SPRING activates S1P by dislodging its inhibitory pro-domain and stabilizing intra-domain contacts. Functionally, SPRING licenses S1P to cleave its cognate substrate, SREBP2. Our findings reveal an activation mechanism for S1P and provide insights into how spatial control of S1P activity underpins cholesterol homeostasis.
Flexible tungsten disulfide superstructure engineering for efficient alkaline hydrogen evolution in anion exchange membrane water electrolysers
Authors: Xie Lingbin , Wang Longlu , Liu Xia , Chen Jianmei , Wen Xixing , Zhao Weiwei , Liu Shujuan , Zhao Qiang
Published: July 2024

Anion exchange membrane (AEM) water electrolysis employing non-precious metal electrocatalysts is a promising strategy for achieving sustainable hydrogen production. However, it still suffers from many challenges, including sluggish alkaline hydrogen evolution reaction (HER) kinetics, insufficient activity and limited lifetime of non-precious metal electrocatalysts for ampere-level-current-density alkaline HER. Here, we report an efficient alkaline HER strategy at industrial-level current density wherein a flexible WS2 superstructure is designed to serve as the cathode catalyst for AEM water electrolysis. The superstructure features bond-free van der Waals interaction among the low Young’s modulus nanosheets to ensure excellent mechanical flexibility, as well as a stepped edge defect structure of nanosheets to realize high catalytic activity and a favorable reaction interface micro-environment. The unique flexible WS2 superstructure can effectively withstand the impact of high-density gas-liquid exchanges and facilitate mass transfer, endowing excellent long-term durability under industrial-scale current density. An AEM electrolyser containing this catalyst at the cathode exhibits a cell voltage of 1.70 V to deliver a constant catalytic current density of 1 A cm−2 over 1000 h with a negligible decay rate of 9.67 μV h−1.
Unveiling the quasiparticle behaviour in the pressure-induced high-Tc phase of an iron-chalcogenide superconductor
Authors: Zajicek Z. , Reiss P. , Graf D. , Prentice J. C. A. , Sadki Y. , Haghighirad A. A. , Coldea A. I.
Published: July 2024

Superconductivity of iron chalocogenides is strongly enhanced under applied pressure yet its underlying pairing mechanism remains elusive. Here, we present a quantum oscillations study up to 45 T in the high-Tc phase of tetragonal FeSe0.82S0.18 up to 22 kbar. Under applied pressure, the quasi-two-dimensional multi-band Fermi surface expands and the effective masses remain large, whereas the superconductivity displays a threefold enhancement. Comparing with chemical pressure tuning of FeSe1−xSx, the Fermi surface expands in a similar manner but the effective masses and Tc are suppressed. These differences may be attributed to the changes in the density of states influenced by the chalcogen height, which could promote stronger spin fluctuations pairing under pressure. Furthermore, our study also reveals unusual scattering and broadening of superconducting transitions in the high-pressure phase, indicating the presence of a complex pairing mechanism.
Floristic diversity and its relationships with human land use varied regionally during the Holocene
Authors: Gordon Jonathan D. , Fagan Brennen , Milner Nicky , Thomas Chris D.
Published: July 2024

Humans have caused growing levels of ecosystem and diversity changes at a global scale in recent centuries but longer-term diversity trends and how they are affected by human impacts are less well understood. Analysing data from 64,305 pollen samples from 1,763 pollen records revealed substantial community changes (turnover) and reductions in diversity (richness and evenness) in the first ~1,500 to ~4,000 years of the Holocene epoch (starting 11,700 years ago). Turnover and diversity generally increased thereafter, starting ~6,000 to ~1,000 years ago, although the timings, magnitudes and even directions of these changes varied among continents, biomes and sites. Here, modelling these diversity changes, we find that most metrics of biodiversity change are associated with human impacts (anthropogenic land-cover change estimates for the last 8,000 years), often positively but the magnitudes, timings and sometimes directions of associations differed among continents and biomes and sites also varied. Once-forested parts of the world tended to exhibit biodiversity increases while open areas tended to decline. These regionally specific relationships between humans and floristic diversity highlight that human–biodiversity relationships have generated positive diversity responses in some locations and negative responses in others, for over 8,000 years.
Unsupervised representation learning on high-dimensional clinical data improves genomic discovery and prediction
Authors: Yun Taedong , Cosentino Justin , Behsaz Babak , McCaw Zachary R. , Hill Davin , Luben Robert , Lai Dongbing , Bates John , Yang Howard , Schwantes-An Tae-Hwi , Zhou Yuchen , Khawaja Anthony P. , Carroll Andrew , Hobbs Brian D. , Cho Michael H. , McLean Cory Y. , Hormozdiari Farhad
Published: July 2024

Although high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS). REGLE can uncover features not captured by existing expert-defined features and enables the creation of accurate disease-specific polygenic risk scores (PRSs) in datasets with very few labeled data. We apply REGLE to perform GWAS on respiratory and circulatory HDCD—spirograms measuring lung function and photoplethysmograms measuring blood volume changes. REGLE replicates known loci while identifying others not previously detected. REGLE are predictive of overall survival, and PRSs constructed from REGLE loci improve disease prediction across multiple biobanks. Overall, REGLE contain clinically relevant information beyond that captured by existing expert-defined features, leading to improved genetic discovery and disease prediction.
Proteomics shows that brain metastases of lung adenocarcinoma overexpress ribosomal proteins in response to gamma knife radiosurgery
Authors: Tong Luqing , Ye Ke , Chen Qun , Wang Xiaoxi , Hu Chi , Xu Qingsheng , Zhou Lihui , Zhan Renya , Tong Ying
Published: July 2024

Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.
Genome wide identification of novel DNA methylation driven prognostic markers in colorectal cancer
Authors: Ma Yuhua , Li Yuanxin , Wen Zhahong , Lai Yining , Kamila Kulaixijiang , Gao Jing , Xu Wang-yang , Gong Chengxiang , Chen Feifan , Shi Liuqing , Zhang Yunzhi , Chen Hanzhang , Zhu Min
Published: July 2024

Colorectal cancer (CRC) stands as a major contributor to cancer-related fatalities within China. There is an urgent need to identify accurate biomarkers for recurrence predicting in CRC. Reduced representation bisulfite sequencing was used to perform a comparative analysis of methylation profiles in tissue samples from 30 recurrence to 30 non-recurrence patients with CRC. Least absolute shrinkage and selection operator method was performed to select the differential methylation regions (DMRs) and built a DNA methylation classifier for predicting recurrence. Based on the identified top DMRs, a methylation classifier was built and consisted of eight hypermethylated DMRs in CRC. The DNA methylation classifier showed high accuracy for predicting recurrence with an area under the receiver operator characteristic curve of 0.825 (95% CI 0.680–0.970). The Kaplan–Meier survival analysis demonstrated that CRC patients with high methylation risk score, evaluated by the DNA methylation classifier, had poorer survival than low risk score (Hazard Ratio 4.349; 95% CI 1.783–10.61, P = 0.002). And only CRC patients with low methylation risk score could acquire benefit from adjuvant therapy. The DNA methylation classifier has been proved as crucial biomarkers for predicting recurrence and exhibited promising prognostic value after curative surgery in patients with CRC.
Emotion regulation skills as a mediator of STEM teachers’ stress, well-being, and burnout
Authors: Farhi Moran , Rubinsten Orly
Published: July 2024

The teaching profession highly stressful, and teachers are often faced with challenging situations. This is particularly the case in STEM (science, technology, engineering, and math) education, which is a uniquely demanding and challenging field. This study examined the role of emotional regulation (ER) skills in STEM teachers’ stress, well-being, and burnout. The sample included 165 STEM teachers in middle and high schools who completed standard online questionnaires on ER, stress, well-being, and burnout. They were also asked to comment on three videos depicting authentic mathematical and pedagogical situations. The results indicated that contrary to popular belief, seniority was not linked with levels of stress, difficulties in ER, lower levels of well-being, or higher levels of burnout. A structural equation model and bootstrapping analysis showed teachers’ levels of stress predicted their well-being, and this link between stress and well-being was mediated by teachers’ level of difficulty in ER. The study highlights the importance of STEM teachers’ well-being and suggests the need to reduce stress and burnout by providing tools for teachers to regulate their emotions in the classroom.
Domestication and exposure to human social stimuli are not sufficient to trigger attachment to humans: a companion pig-dog comparative study
Authors: Gábor Anna , Pérez Fraga Paula , Gácsi Márta , Gerencsér Linda , Andics Attila
Published: July 2024

Dogs exhibit human-analogue attachment to their owners, with similar function and mechanisms to that of infant-mother bond, but its origin is unclear. Comparative studies on socialised wolves and dogs emphasise genetic influence in dogs' preparedness for attachment to humans. We aimed to reveal if this genetic effect stems from general domestication or artificial selection that increased dogs' dependence on humans. We assessed and compared behavioural patterns of young companion pigs and dogs using a Strange Situation Test. Dogs but not pigs exhibited distinct behaviours towards their owner and a stranger along attachment-specific variables, so only dogs’ relevant behaviours fulfilled attachment criteria. From the observed behaviours, three factors were formed: Attachment (to the owner), Anxiety (in a strange situation), and Acceptance (of a stranger). Results indicate (1) higher Attachment scores in dogs than pigs, (2) greater Acceptance scores in pigs, (3) positive correlation of Attachment and Anxiety in both, (4) similar time tendency of pigs' Attachment and Acceptance scores. These suggest that in pigs, domestication and early exposure to human social stimuli did not trigger attachment to humans. Thus, along with species predispositions, the unique dog-owner attachment can be facilitated by artificial selection that increased dogs' dependence on humans.
Urea production via photocatalytic coupling of mixed gases (CO2/NH3) using Mo(MnO4)5 supported on Ce-BTC as nano-composite catalyst
Authors: El-Shahat Mahmoud , Abdelhameed Reda M.
Published: July 2024

Urea used in fertilization and feed supplement, as well as a starting material for the manufacture of plastics and drugs. Urea is most commonly produced by reacting carbon dioxide with ammonia at high temperature. Photocatalysis has gained attention as a sustainable pathway for performing urea. This work focus on designing very active photocatalysts based on cerium organic framework (Ce-BTC) doped with metal oxide nanoparticles (molybdenum permanganate, Mo(MnO4)5) for production of urea from coupling of ammonia with carbon dioxide. The prepared materials were characterized using different spectral analysis and the morphology was analysed using microscopic data. The effect of catalyst loading on the production rate of urea was investigated and the obtained results showed speed rate of urea production with high production yield at low temperature. The recyclability tests confirmed the sustainability of the prepared photocatlysts (Mo(MnO4)5@Ce-BTC) which supported the beneficial of the photocatalysis process in urea production.
Human health risk assessment of heavy metals in vegetables of Bangladesh
Authors: Chowdhury Akibul Islam , Shill Lincon Chandra , Raihan M. Maruf , Rashid Rumana , Bhuiyan Md. Nizamul Hoque , Reza Sompa , Alam Mohammad Rahanur
Published: July 2024

This study aims to evaluate the heavy metal concentration in fifteen species of vegetables as well as associated health risk. Atomic absorption spectrometry is used to assess heavy metals. The mean concentrations of Pb, Cd, Cr, Ni and Fe in vegetables were 4.78, 0.713, 9.266, 0.083, 5.06 mg/kg/fw exceeding the reference value of FAO/WHO indicating unsafe to consumption. Based on principal component analysis, the Pb, Cr, Ni and Fe are from same sources. Health risk was estimated in terms of estimated daily intake (EDI), target hazard quotient, hazard index (HI) and cancer risk (CR). The EDI values of metals except Cr were found to be lower than maximum tolerable daily intake (MTDI). The total THQs of metals were > 1 indicating non-carcinogenic health risk. The individual HI values for vegetables except potato (0.831) and total HI values were found to be > 1 (94.747). The TCR of Pb, Cd and Cr were > 1.0E−04 which indicating carcinogenic risk. Fruit and pod vegetables contribute much in carcinogenic risk for Pb and Cr whereas fruit, root and stems vegetables for Cd. The study revealed potential human health risk associated with the consumption of different types of vegetables in Bangladeshi adult population that might assist the regulatory bodies to develop new strategies to minimize the risk to human.
Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis
Authors: Yasuda Takeshi , Takagi Tomohisa , Asaeda Kohei , Hashimoto Hikaru , Kajiwara Mariko , Azuma Yuka , Kitae Hiroaki , Hirai Yasuko , Mizushima Katsura , Doi Toshifumi , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Uchiyama Kazuhiko , Ishikawa Takeshi , Konishi Hideyuki , Ukawa Yuichi , Kohara Akiko , Kudoh Masatake , Inoue Ryo , Naito Yuji , Itoh Yoshito
Published: July 2024

Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.
Immunomodulatory of sesquiterpenoids and sesquiterpenoid dimers-based toll-like receptor 4 (TLR4) from Dysoxylum parasiticum stem bark
Authors: Naini Al Arofatus , Mayanti Tri , Hilmayanti Erina , Huang Xuhao , Kabayama Kazuya , Shimoyama Atsushi , Manabe Yoshiyuki , Fukase Koichi , Supratman Unang
Published: July 2024

In recent decades, the interest in natural products with immunomodulatory properties has increased due to their therapeutic potential. These products have a wider range of pharmacological activities and demonstrate lower toxicity levels when compared to their synthetic counterparts. Therefore, this study aimed to investigate the immunomodulatory effects of sesquiterpenoids (SQs) and sesquiterpenoid dimers (SQDs) isolated from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark on human and murine cells, particularly focusing on toll-like receptor 4 (TLR4). Utilizing the secreted alkaline phosphatase (SEAP) assay on engineered human and murine TLR4 of HEK-Blue cells, antagonist TLR4 compounds were identified, including SQs 6, 9, and 10, as well as SQDs 17 and 22. The results showed that 10-hydroxyl-15-oxo-α-cadinol (9) had a potent ability to reduce TLR4 activation induced by LPS stimulation, with minimal toxicity observed in both human and murine cells. The SEAP assay also revealed diverse immune regulatory effects for the same ligand. For instance, SQs 12, 14, and 16 transitioned from antagonism on human to murine TLR4. The SQs (4, 7, 11, and 15) and SQDs (18–20) offered partial antagonist effect exclusively on murine TLR4. Furthermore, these selected SQs and SQDs were assessed for their influence on the production of proinflammatory cytokines TNF-α, IL-1α, IL-1β, and IL-6 of the NF-κB signaling pathway in human and murine macrophage cell lines, showing a dose-dependent manner. Additionally, a brief discussion on the structure-activity relationship was presented.
Combination immunohistochemistry for CK5/6, p63, GATA6, and HNF4a predicts clinical outcome in treatment-naïve pancreatic ductal adenocarcinoma
Authors: Shibayama Takahiro , Hayashi Akimasa , Toki Masao , Kitahama Keiichiro , Ho Yu-Jui , Kato Kenichiro , Yamada Takahiro , Kawamoto Sho , Kambayashi Komei , Ochiai Kazushige , Gondo Koichi , Okano Naohiro , Melchor Jerry P. , Iacobuzio-Donahue Christine A. , Sakamoto Yoshihiro , Hisamatsu Tadakazu , Shibahara Junji
Published: July 2024

Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p < 0.001) and demonstrated the worst overall survival among our cohort (p = 0.004). IHC expression subtype (Transitional, Basal vs Classical) was an independent poor prognosticator in multivariate analysis [HR 1.58 (95% CI 1.01–2.38), p = 0.047]. Furthermore, CK5/6 expression was an independent poor prognostic factor in histological glandular type PDAC [HR 2.82 (95% CI 1.31–6.08), p = 0.008]. Our results suggest that IHC expression patterns successfully predict molecular features indicative of the Basal-like subgroup in advanced PDAC. These results provide the basis for appropriate stratification for therapeutic selection and prognostic estimation of advanced PDAC in a simplified manner.
The discovery of the church of Rungholt, a landmark for the drowned medieval landscapes of the Wadden Sea World Heritage
Authors: Wilken Dennis , Hadler Hanna , Majchczack Bente Sven , Blankenfeldt Ruth , Auge Oliver , Bäumler Sarah , Bienen-Scholt Dirk , Ickerodt Ulf , Klooß Stefanie , Reiß Antonia , Willershäuser Timo , Rabbel Wolfgang , Vött Andreas
Published: July 2024

The UNESCO World Heritage Wadden Sea holds remains of a medieval cultural landscape shaped by interactions between man and natural forces. From the Netherlands to Denmark, human efforts of cultivating low-lying areas created a unique coastal landscape. Since the Middle Ages, storm floods widely drowned embanked cultural land and especially affected North Frisia (Germany), where once fertile marshland was permanently turned into tidal flats. One key region, the Edomsharde, was widely destroyed in 1362 AD. Medieval settlement remains still occur in the tidal flats around the island Hallig Südfall and are commonly associated with Edomsharde’s trading centre Rungholt—ever since a symbol for the region’s drowned landscapes and focus of this study. We present a first-time comprehensive reconstruction of this medieval settlement by means of new geophysical, geoarchaeological and archaeological data. Our results reveal remains of up to 64 newly found and rectified dwelling mounds, abundant drainage ditches, a seadike, and especially the discovery of Edomshardes’s main church as important landmark in this former cultural landscape. These finds together with the documented imported goods confirm a thriving society, involved in transregional trade and thereby close a significant gap in medieval history not only for North Frisia, but the entire Wadden Sea region.
Functional data geometric morphometrics with machine learning for craniodental shape classification in shrews
Authors: Pillay Aneesha Balachandran , Pathmanathan Dharini , Dabo-Niang Sophie , Abu Arpah , Omar Hasmahzaiti
Published: July 2024

This work proposes a functional data analysis approach for morphometrics in classifying three shrew species (S. murinus, C. monticola, and C. malayana) from Peninsular Malaysia. Functional data geometric morphometrics (FDGM) for 2D landmark data is introduced and its performance is compared with classical geometric morphometrics (GM). The FDGM approach converts 2D landmark data into continuous curves, which are then represented as linear combinations of basis functions. The landmark data was obtained from 89 crania of shrew specimens based on three craniodental views (dorsal, jaw, and lateral). Principal component analysis and linear discriminant analysis were applied to both GM and FDGM methods to classify the three shrew species. This study also compared four machine learning approaches (naïve Bayes, support vector machine, random forest, and generalised linear model) using predicted PC scores obtained from both methods (a combination of all three craniodental views and individual views). The analyses favoured FDGM and the dorsal view was the best view for distinguishing the three species.
Climate change will lead to range shifts and genetic diversity losses of dung beetles in the Gobi Desert and Mongolian Steppe
Authors: Lim Changseob , Kang Ji Hyoun , Bayartogtokh Badamdorj , Bae Yeon Jae
Published: July 2024

Desertification is known to be a major threat to biodiversity, yet our understanding of the consequent decline in biodiversity remains insufficient. Here, we predicted climate change-induced range shifts and genetic diversity losses in three model dung beetles: Colobopterus erraticus, Cheironitis eumenes, and Gymnopleurus mopsus, distributed across the Gobi Desert and Mongolian Steppe, areas known for desertification. Phylogeographic analyses of mitochondrial COI sequences and species distribution modeling, based on extensive field investigations spanning 14 years, were performed. Species confined to a single biome were predicted to contract and shift their distribution in response to climate change, whereas widespread species was predicted to expand even if affected by range shifts. We indicated that all species are expected to experience significant haplotype losses, yet the presence of high singleton frequencies and low genetic divergence across geographic configurations and lineages mitigate loss of genetic diversity. Notably, Cheironitis eumenes, a desert species with low genetic diversity, appears to be the most vulnerable to climate change due to the extensive degradation in the Gobi Desert. This is the first study to predict the response of insects to desertification in the Gobi Desert. Our findings highlight that dung beetles in the Gobi Desert and Mongolian Steppe might experience high rates of occupancy turnover and genetic loss, which could reshuffle the species composition.
Examining the impact of differing caffeine dosages in conjunction with plyometric training on physiological adaptations in basketball players
Authors: Wu Siyuan , Jiang Han
Published: July 2024

The aim of the current study was to investigate the effects of ingesting different dosages of caffeine (CAF) prior to plyometric jump training (PJT) on sport-related performance and physiological parameters in male basketball players. Twenty-four young athletes were randomly divided into 3 groups and performed 6 weeks of PJT while consuming 3 mg·kg–1 of body mass caffeine (CAF3, n = 8), 6 mg·kg–1 body mass caffeine (CAF6, n = 8) or placebo (PL; n = 8) one hour prior to each training session. Before and after the 6-week PJT, the players were evaluated for field-based basketball-specific performance measures (vertical jump, 20-m sprint, Illinois change of direction speed [CODS], and maximal strength) and lab-based physiological (aerobic capacity and anaerobic power) parameters. CAF3, CAF6, and PL groups demonstrated significant improvements in vertical jump (ES = 1.07, 1.45, and 1.1, respectively), 20-m sprint (ES = – 0.50, – 0.61, and – 0.36), change of direction performance (ES = – 1.22, – 1.26, and – 1.09), maximal strength (ES = 1.68, 2.29, and 1.17), maximum oxygen uptake (V̇O2max) (ES = 1.09, 1.59, and 0.92), and peak (ES = 1.82, 1.85, and 0.82) and average power output (ES = 1.39, 1.32, and 1.07) after 6 weeks of training. Comparative analysis of individual adaptive responses to training indicated that the CAF6 led to insignificantly greater effects in vertical jump (ES = 1.45), maximal strength (ES = 2.29), and V̇O2max (ES = 1.59) with lower residuals in individual changes and lower coefficient of variations (CV) in mean group changes. Regarding sprint and CODS performance, both experimental groups indicated similar changes, residuals in individual changes, and CVs in mean group changes. Overall, consuming 6 mg·kg–1 body mass caffeine induces superior adaptations in aerobic fitness, anaerobic power, and sport-specific performance measures, with lower inter-individual variability in the adaptations and more homogenized changes over the training period.
Microseismic comprehensive evaluation method for coal burst: a case study in the Zhaolou Coal Mine
Authors: Zhang Heng , Liang Liang , Lin Na , Zhang Shuai , Cui Miao-miao , Yang Zhong-gang
Published: July 2024

To explore the multiparameter precursor characteristics of pre- and post-coal burst. Based on a coal burst of LW 1305 in the Zhaolou Coal Mine, an early warning method combining stress‒strain curve and microseismic multiparameter is proposed. The research results show that coal burst was induced by the intrinsic static high-stress concentration and the strong external impact loading generated by fracturing of the key stratum. The precursors mainly characterize the enhancement trend of the S value, the sudden and sharp increase in the A(t) value, the continuous and abnormal decrease in the b value, the increasing absolute value of Z sharply and larger than 2, the continuous and abnormal decrease in the Qt value, and the dominant frequency moving to the low-frequency band. Essentially, many micro-fissures inside the key stratum initiated, converged and connected to form macro-fractures, which was verified by the attenuation rate of the K value. Considering the time-varying effect of the overlying stratum movement, the curves of the six parameters agree well with those of stress vs. strain, which indicates that it is reasonable to take the observed zone as a whole system to investigate the variation in the multiple parameters and fracturing of the key stratum. The research results can be applied to the monitoring, early warning and control of coal burst so that effective safety measures can be taken in real time.
Evaluation of hydrogen production via steam reforming and partial oxidation of dimethyl ether using response surface methodology and artificial neural network
Authors: Mansouri Karim , Bahmanzadegan Fatemeh , Ghaemi Ahad
Published: July 2024

This study aims to develop two models for thermodynamic data on hydrogen generation from the combined processes of dimethyl ether steam reforming and partial oxidation, applying artificial neural networks (ANN) and response surface methodology (RSM). Three factors are recognized as important determinants for the hydrogen and carbon monoxide mole fractions. The RSM used the quadratic model to formulate two correlations for the outcomes. The ANN modeling used two algorithms, namely multilayer perceptron (MLP) and radial basis function (RBF). The optimum configuration for the MLP, employing the Levenberg–Marquardt (trainlm) algorithm, consisted of three hidden layers with 15, 10, and 5 neurons, respectively. The ideal RBF configuration contained a total of 80 neurons. The optimum configuration of ANN achieved the best mean squared error (MSE) performance of 3.95e−05 for the hydrogen mole fraction and 4.88e−05 for the carbon monoxide mole fraction after nine epochs. Each of the ANN and RSM models produced accurate predictions of the actual data. The prediction performance of the ANN model was 0.9994, which is higher than the RSM model's 0.9771. The optimal condition was obtained at O/C of 0.4, S/C of 2.5, and temperature of 250 °C to achieve the highest H2 production with the lowest CO emission.
A health economic pilot study comparing two diabetic retinopathy screening strategies
Authors: Sauesund Ellen Steffenssen , Hertzberg Silvia N. W. , Jørstad Øystein Kalsnes , Moe Morten Carstens , Erke Maja Gran , Fosmark Dag Sigurd , Petrovski Goran
Published: July 2024

To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.
LOV1 protein of Pseudomonas cichorii JBC1 modulates its virulence and lifestyles in response to blue light
Authors: Khanh Nguyen Van , Lee Yong Hoon
Published: July 2024

Bacteria perceive light signals via photoreceptors and modulate many physiological and genetic processes. The impacts played by light, oxygen, or voltage (LOV) and blue light (BL) photosensory proteins on the virulence-related traits of plant bacterial pathogens are diverse and complex. In this study, we identified LOV protein (Pc-LOV1) from Pseudomonas cichorii JBC1 (PcJBC1) and characterized its function using LOV1-deficient mutant (JBC1Δlov1). In the dark state, the recombinant Pc-LOV1 protein showed an absorption band in UV-A region with a double peak at 340 nm and 365 nm, and within the blue-region, it exhibited a main absorption at 448 nm along with two shoulder peaks at 425 nm and 475 nm, which is a typical feature of oxidized flavin within LOV domain. The adduct-state lifetime (τrec) of Pc-LOV1 was 67.03 ± 4.34 min at 25 °C. BL negatively influenced the virulence of PcJBC1 and the virulence of JBC1Δlov1 increased irrespective of BL, indicating that Pc-LOV1 negatively regulates PcJBC1 virulence. Pc-LOV1 and BL positively regulated traits relevant to colonization on plant surface, such as adhesion to the plant tissue and biofilm formation. In contrast, swarming motility, exopolysaccharide production, and siderophore synthesis were negatively controlled. Gene expression supported the modulation of bacterial features by Pc-LOV1. Overall, our results suggest that the LOV photosensory system plays crucial roles in the adaptive responses and virulence of the bacterial pathogen PcJBC1. The roles of other photoreceptors, sensing of other wavelengths, and signal networking require further investigation.
Synthesis, biological evaluation, molecular docking, and MD simulation of novel 2,4-disubstituted quinazoline derivatives as selective butyrylcholinesterase inhibitors and antioxidant agents
Authors: Sadeghian Sara , Razmi Raziyeh , Khabnadideh Soghra , Khoshneviszadeh Mehdi , Mardaneh Pegah , Talashan Arman , Pirouti Arman , Khebre Fatemeh , Zahmatkesh Zahra , Rezaei Zahra
Published: July 2024

Alzheimer’s disease is the most prevalent neurodegenerative disorder characterized by significant memory loss and cognitive impairments. Studies have shown that the expression level and activity of the butyrylcholinesterase enzyme increases significantly in the late stages of Alzheimer’s disease, so butyrylcholinesterase can be considered as a promising therapeutic target for potential Alzheimer’s treatments. In the present study, a novel series of 2,4-disubstituted quinazoline derivatives (6a–j) were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinestrase (BuChE) enzymes, as well as for their antioxidant activities. The biological evaluation revealed that compounds 6f, 6h, and 6j showed potent inhibitory activities against eqBuChE, with IC50 values of 0.52, 6.74, and 3.65 µM, respectively. These potent compounds showed high selectivity for eqBuChE over eelAChE. The kinetic study demonstrated a mixed-type inhibition pattern for both enzymes, which revealed that the potent compounds might be able to bind to both the catalytic active site and peripheral anionic site of eelAChE and eqBuChE. In addition, molecular docking studies and molecular dynamic simulations indicated that potent compounds have favorable interactions with the active sites of BuChE. The antioxidant screening showed that compounds 6b, 6c, and 6j displayed superior scavenging capabilities compared to the other compounds. The obtained results suggest that compounds 6f, 6h, and 6j are promising lead compounds for the further development of new potent and selective BuChE inhibitors.