bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbital hybridization of donor and acceptor to enhance the conductivity of mixed-stack complexes
Authors: Fujino Tomoko , Kameyama Ryohei , Onozuka Kota , Matsuo Kazuki , Dekura Shun , Miyamoto Tatsuya , Guo Zijing , Okamoto Hiroshi , Nakamura Toshikazu , Yoshimi Kazuyoshi , Kitou Shunsuke , Arima Taka-hisa , Sato Hiroyasu , Yamamoto Kaoru , Takahashi Akira , Sawa Hiroshi , Nakamura Yuiga , Mori Hatsumi
Published: April 2024

Mixed-stack complexes which comprise columns of alternating donors and acceptors are organic conductors with typically poor electrical conductivity because they are either in a neutral or highly ionic state. This indicates that conductive carriers are insufficient or are mainly localized. In this study, mixed-stack complexes that uniquely exist at the neutral–ionic boundary were synthesized by combining donors (bis(3,4-ethylenedichalcogenothiophene)) and acceptors (fluorinated tetracyanoquinodimethanes) with similar energy levels and orbital symmetry between the highest occupied molecular orbital of the donor and the lowest unoccupied molecular orbital of the acceptor. Surprisingly, the orbitals were highly hybridized in the single-crystal complexes, enhancing the room-temperature conductivity (10−4–0.1 S cm−1) of mixed-stack complexes. Specifically, the maximum conductivity was the highest reported for single-crystal mixed-stack complexes under ambient pressures. The unique electronic structures at the neutral–ionic boundary exhibited structural perturbations between their electron-itinerant and localized states, causing abrupt temperature-dependent changes in their electrical, optical, dielectric, and magnetic properties.
Using strain to uncover the interplay between two- and three-dimensional charge density waves in high-temperature superconducting YBa2Cu3Oy
Authors: Vinograd I. , Souliou S. M. , Haghighirad A.-A. , Lacmann T. , Caplan Y. , Frachet M. , Merz M. , Garbarino G. , Liu Y. , Nakata S. , Ishida K. , Noad H. M. L. , Minola M. , Keimer B. , Orgad D. , Hicks C. W. , Le Tacon M.
Published: April 2024

Uniaxial pressure provides an efficient approach to control charge density waves in YBa2Cu3Oy. It can enhance the correlation volume of ubiquitous short-range two-dimensional charge-density-wave correlations, and induces a long-range three-dimensional charge density wave, otherwise only accessible at large magnetic fields. Here, we use x-ray diffraction to study the strain dependence of these charge density waves and uncover direct evidence for a form of competition between them. We show that this interplay is qualitatively described by including strain effects in a nonlinear sigma model of competing superconducting and charge-density-wave orders. Our analysis suggests that strain stabilizes the 3D charge density wave in the regions between disorder-pinned domains of 2D charge density waves, and that the two orders compete at the boundaries of these domains. No signatures of discommensurations nor of pair density waves are observed. From a broader perspective, our results underscore the potential of strain tuning as a powerful tool for probing competing orders in quantum materials.
Distinct skyrmion phases at room temperature in two-dimensional ferromagnet Fe3GaTe2
Authors: Lv Xiaowei , Lv Hualiang , Huang Yalei , Zhang Ruixuan , Qin Guanhua , Dong Yihui , Liu Min , Pei Ke , Cao Guixin , Zhang Jincang , Lai Yuxiang , Che Renchao
Published: April 2024

Distinct skyrmion phases at room temperature hosted by one material offer additional degree of freedom for the design of topology-based compact and energetically-efficient spintronic devices. The field has been extended to low-dimensional magnets with the discovery of magnetism in two-dimensional van der Waals magnets. However, creating multiple skyrmion phases in 2D magnets, especially above room temperature, remains a major challenge. Here, we report the experimental observation of mixed-type skyrmions, exhibiting both Bloch and hybrid characteristics, in a room-temperature ferromagnet Fe3GaTe2. Analysis of the magnetic intensities under varied imaging conditions coupled with complementary simulations reveal that spontaneous Bloch skyrmions exist as the magnetic ground state with the coexistence of hybrid stripes domain, on account of the interplay between the dipolar interaction and the Dzyaloshinskii-Moriya interaction. Moreover, hybrid skyrmions are created and their coexisting phases with Bloch skyrmions exhibit considerably high thermostability, enduring up to 328 K. The findings open perspectives for 2D spintronic devices incorporating distinct skyrmion phases at room temperature.
Weakened western Indian Ocean dominance on Antarctic sea ice variability in a changing climate
Authors: Zhang Li , Ren Xuya , Cai Wenju , Li Xichen , Wu Lixin
Published: April 2024

Patterns of sea surface temperature (SST) anomalies of the Indian Ocean Dipole (IOD) exhibit strong diversity, ranging from being dominated by the western tropical Indian Ocean (WTIO) to the eastern tropical Indian Ocean (ETIO). Whether and how the different types of IOD variability patterns affect the variability of Antarctic sea ice is not known, nor is how the impact may change in a warming climate. Here, we find that the leading mode of austral spring Antarctic sea ice variability is dominated by WTIO SST variability rather than ETIO SST or El Niño–Southern Oscillation. WTIO warm SST anomalies excite a poleward-propagating Rossby wave, inducing a tri-polar anomaly pattern characterized by a decrease in sea ice near the Amundsen Sea but an increase in regions on both sides. Such impact has been weakening in the two decades post-2000, accompanied by weakened WTIO SST variability. Under greenhouse warming, climate models project a decrease in WTIO SST variability, suggesting that the reduced impact on Antarctic sea ice from the IOD will likely to continue, facilitating a fast decline of Antarctic sea ice.
Insights into the inhibition of protospacer integration via direct interaction between Cas2 and AcrVA5
Authors: Bi Mingfang , Su Wenjing , Li Jiafu , Mo Xiaobing
Published: April 2024

Spacer acquisition step in CRISPR-Cas system involves the recognition and subsequent integration of protospacer by the Cas1-Cas2 complex in CRISPR-Cas systems. Here we report an anti-CRISPR protein, AcrVA5, and reveal the mechanisms by which it strongly inhibits protospacer integration. Our biochemical data shows that the integration by Cas1-Cas2 was abrogated in the presence of AcrVA5. AcrVA5 exhibits low binding affinity towards Cas2 and acetylates Cas2 at Lys55 on the binding interface of the Cas2 and AcrVA5 N-terminal peptide complex to inhibit the Cas2-mediated endonuclease activity. Moreover, a detailed structural comparison between our crystal structure and homolog structure shows that binding of AcrVA5 to Cas2 causes steric hindrance to the neighboring protospacer resulting in the partial disassembly of the Cas1-Cas2 and protospacer complex, as demonstrated by electrophoretic mobility shift assay. Our study focuses on this mechanism of spacer acquisition inhibition and provides insights into the biology of CRISPR-Cas systems.
Stroke-volume-allocation model enabling wearable sensors for vascular age and cardiovascular disease assessment
Authors: Qiu Shirong , Yan Bryan P. Y. , Zhao Ni
Published: April 2024

Frequent and unobtrusive monitoring of cardiovascular conditions with consumer electronics is a widely pursued goal, since it provides the most economic and effective way of preventing and managing cardiovascular diseases (CVDs) ─ the leading causes of death worldwide. However, most current wearable and flexible devices can only support the measurement of one or two types of vital signs, such as heart rate and blood oxygen level, due to the lack of physiological models to link the measured signals to cardiovascular conditions. Here, we report a stroke-volume allocation (SVA) model to quantify the cushioning function of arteries and empower nearly all existing cardiac sensors with new functions, including arterial stiffness evaluation, dynamic blood pressure tracking and classification of CVD-related heart damage. Large-scale clinical data testing involving a hybrid dataset taken from 6 hospitals/research institutes (9 open databases and 4 self-built databases from 878 subjects in total) and diverse measurement approaches was carried out to validate the SVA model. The results show that the SVA-based parameters correlate well with the gold-standard measurements in arterial stiffness and blood pressure and outperform the commonly used vital sign (e.g., blood pressure) alone in detecting abnormalities in cardiovascular systems.
Single-mitosis dissection of acute and chronic DNA mutagenesis and repair
Authors: Ginno Paul Adrian , Borgers Helena , Ernst Christina , Schneider Anja , Behm Mikaela , Aitken Sarah J. , Taylor Martin S. , Odom Duncan T.
Published: April 2024

How chronic mutational processes and punctuated bursts of DNA damage drive evolution of the cancer genome is poorly understood. Here, we demonstrate a strategy to disentangle and quantify distinct mechanisms underlying genome evolution in single cells, during single mitoses and at single-strand resolution. To distinguish between chronic (reactive oxygen species (ROS)) and acute (ultraviolet light (UV)) mutagenesis, we microfluidically separate pairs of sister cells from the first mitosis following burst UV damage. Strikingly, UV mutations manifest as sister-specific events, revealing mirror-image mutation phasing genome-wide. In contrast, ROS mutagenesis in transcribed regions is reduced strand agnostically. Successive rounds of genome replication over persisting UV damage drives multiallelic variation at CC dinucleotides. Finally, we show that mutation phasing can be resolved to single strands across the entire genome of liver tumors from F1 mice. This strategy can be broadly used to distinguish the contributions of overlapping cancer relevant mutational processes.
TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma
Authors: Yi Heng , Yang Qijun , Repaci Charlie , Lee Cheolmin Matthew , Heo Gyujin , Timsina Jigyasha , Gorijala Priyanka , Yang Chengran , Budde John , Wang Lihua , Cruchaga Carlos , Sung Yun Ju
Published: April 2024

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.
A construction waste landfill dataset of two districts in Beijing, China from high resolution satellite images
Authors: Lin Shaofu , Huang Lei , Liu Xiliang , Chen Guihong , Fu Zhe
Published: April 2024

Construction waste is unavoidable in the process of urban development, causing serious environmental pollution. Accurate assessment of municipal construction waste generation requires building construction waste identification models using deep learning technology. However, this process requires high-quality public datasets for model training and validation. This study utilizes Google Earth and GF-2 images as the data source to construct a specific dataset of construction waste landfills in the Changping and Daxing districts of Beijing, China. This dataset contains 3,653 samples of the original image areas and provides mask-labeled images in the semantic segmentation domains. Each pixel within a construction waste landfill is classified into 4 categories of the image areas, including background area, vacant landfillable area, engineering facility area, and waste dumping area. The dataset contains 237,115,531 pixels of construction waste and 49,724,513 pixels of engineering facilities. The pixel-level semantic segmentation labels are provided to quantify the construction waste yield, which can serve as the basic data for construction waste extraction and yield estimation both for academic and industrial research.
Out-of-equilibrium charge redistribution in a copper-oxide based superconductor by time-resolved X-ray photoelectron spectroscopy
Authors: Puntel Denny , Kutnyakhov Dmytro , Wenthaus Lukas , Scholz Markus , Wind Nils O. , Heber Michael , Brenner Günter , Gu Genda , Cava Robert J. , Bronsch Wibke , Cilento Federico , Parmigiani Fulvio , Pressacco Federico
Published: April 2024

Charge-transfer excitations are of paramount importance for understanding the electronic structure of copper-oxide based high-temperature superconductors. In this study, we investigate the response of a Bi$$_2$$

2

Sr$$_2$$

2

CaCu$$_2$$

2

O$$_{\textrm{8}+ \delta }$$

8
+
δ

crystal to the charge redistribution induced by an infrared ultrashort pulse. Element-selective time-resolved core-level photoelectron spectroscopy with a high energy resolution allows disentangling the dynamics of oxygen ions with different coordination and bonds thanks to their different chemical shifts. Our experiment shows that the O 1s component arising from the Cu–O planes is significantly perturbed by the infrared light pulse. Conversely, the apical oxygen, also coordinated with Sr ions in the Sr-O planes, remains unaffected. This result highlights the peculiar behavior of the electronic structure of the Cu–O planes. It also unlocks the way to study the out-of-equilibrium electronic structure of copper-oxide-based high-temperature superconductors by identifying the O 1s core-level emission originating from the oxygen ions in the Cu–O planes. This ability could be critical to gain information about the strongly-correlated electron ultrafast dynamical mechanisms in the Cu–O plane in the normal and superconducting phases.
Helmet wearing detection algorithm based on improved YOLOv5
Authors: Liu Yiping , Jiang Benchi , He Huan , Chen Zhijun , Xu Zhenfa
Published: April 2024

In industrial production, workers need to wear safety helmets at all times. However, due to different lighting, viewing angles, and the tendency of people to block each other, the precision of target detection is not high enough. Aiming at this problem, a real-time detection of helmets was achieved by improving the YOLOv5 algorithm. This algorithm introduces the lightweight network structure FasterNet, which uses partial convolution as the main operator to reduce the amount of calculations and parameters of the network; the boundary regression loss function Wise-IoU loss function with a dynamic focusing mechanism replaces the original loss function in YOLOv5; finally, the CBAM attention mechanism is introduced to obtain global context information and improve the detection ability of small targets. The experimental results show that the parameters of the improved YOLOv5 model are reduced by 12.68%, the computational amount is reduced by 10.8%, the mAP is increased from 88.3 to 92.3%, and the inference time is reduced by 81.5%, which is better than the performance of the original model and can detect helmet wearing effectively and in real time.
TRIM33 loss in multiple myeloma is associated with genomic instability and sensitivity to PARP inhibitors
Authors: McAvera Roisin M. , Morgan Jonathan J. , Herrero Ana B. , Mills Ken I. , Crawford Lisa J.
Published: April 2024

Deletions of chromosome 1p (del(1p)) are a recurrent genomic aberration associated with poor outcome in Multiple myeloma (MM.) TRIM33, an E3 ligase and transcriptional co-repressor, is located within a commonly deleted region at 1p13.2. TRIM33 is reported to play a role in the regulation of mitosis and PARP-dependent DNA damage response (DDR), both of which are important for maintenance of genome stability. Here, we demonstrate that MM patients with loss of TRIM33 exhibit increased chromosomal instability and poor outcome. Through knockdown studies, we show that TRIM33 loss induces a DDR defect, leading to accumulation of DNA double strand breaks (DSBs) and slower DNA repair kinetics, along with reduced efficiency of non-homologous end joining (NHEJ). Furthermore, TRIM33 loss results in dysregulated ubiquitination of ALC1, an important regulator of response to PARP inhibition. We show that TRIM33 knockdown sensitizes MM cells to the PARP inhibitor Olaparib, and this is synergistic with the standard of care therapy bortezomib, even in co-culture with bone marrow stromal cells (BMSCs). These findings suggest that TRIM33 loss contributes to the pathogenesis of high-risk MM and that this may be therapeutically exploited through the use of PARP inhibitors.
Estimates of lithium mass yields from produced water sourced from the Devonian-aged Marcellus Shale
Authors: Mackey Justin , Bain Daniel J. , Lackey Greg , Gardiner James , Gulliver Djuna , Kutchko Barbara
Published: April 2024

Decarbonatization initiatives have rapidly increased the demand for lithium. This study uses public waste compliance reports and Monte Carlo approaches to estimate total lithium mass yields from produced water (PW) sourced from the Marcellus Shale in Pennsylvania (PA). Statewide, Marcellus Shale PW has substantial extractable lithium, however, concentrations, production volumes and extraction efficiencies vary between the northeast and southwest operating zones. Annual estimates suggest statewide lithium mass yields of approximately 1160 (95% CI 1140–1180) metric tons (mt) per year. Production decline curve analysis on PW volumes reveal cumulative volumetric disparities between the northeast (median = 2.89 X 107 L/10-year) and southwest (median = 5.56 × 107 L/10-year) regions of the state, influencing lithium yield estimates of individual wells in southwest [2.90 (95% CI 2.80–2.99) mt/10-year] and northeast [1.96 (CI 1.86–2.07) mt/10-year] PA. Moreover, Mg/Li mass ratios vary regionally, where NE PA are low Mg/Li fluids, having a median Mg/Li mass ratio of 5.39 (IQR, 2.66–7.26) and SW PA PW is higher with a median Mg/Li mass ratio of 17.8 (IQR, 14.3–20.7). These estimates indicate substantial lithium yields from Marcellus PW, though regional variability in chemistry and production may impact recovery efficiencies.
Analytic representative element rate decline models for naturally fractured reservoir depletion
Authors: Hazlett R. D. , Syrymov T. , Younis R.
Published: April 2024

Representative single anisotropic matrix block 2D Green’s function models for depletion through fully-penetrating, vertical fractures through different numbers of fracture faces are constructed that analytically capture both fracture and block depletion with fracture-matrix mass transfer. The 1D Green’s function for a fracture system is likewise solved in terms of the time evolution of average fracture pressure. While transient average pressure values are not inherently measurable, they are transformed into cumulative production or instantaneous flowrate values, thus producing new rate decline model functional forms. Primary variables in assembling the interacting systems model are the volume ratio, Vf /Vm, permeability ratio, kf /kx, and geometry, (a/b)(ky/kx), with the last term accounting for both block shape and permeability anisotropy. We construct interacting systems models in terms of various ratios of Vf /Vm, and kf /kx for three fracture architecture prototypes: representative matrix blocks depleted by 4, 2, or 1 contacting fractures. The single matrix block models can be migrated to ones for heterogeneous systems using superposition and matrix block distributions, as demonstrated with a binary distribution of block sizes with variable fractions. Analytic solutions for rate decline problems can be used to understand the production signatures of naturally fractured reservoirs and interpretation of fracture volume fraction, permeability ratio, average matrix block size, and measures of heterogeneity.
Motif-based community detection in heterogeneous multilayer networks
Authors: Liu Yafang , Li Aiwen , Zeng An , Zhou Jianlin , Fan Ying , Di Zengru
Published: April 2024

Multilayer networks composed of intralayer edges and interlayer edges are an important type of complex networks. Considering the heterogeneity of nodes and edges, it is necessary to design more reasonable and diverse community detection methods for multilayer networks. Existing research on community detection in multilayer networks mainly focuses on multiplexing networks (where the nodes are homogeneous and the edges are heterogeneous), but few studies have focused on heterogeneous multilayer networks where both nodes and edges represent different semantics. In this paper, we studied community detection on heterogeneous multilayer networks and proposed a motif-based detection algorithm. First, the communities and motifs of multilayer networks are defined, especially the interlayer motifs. Then, the modularity of multilayer networks based on these motifs is designed, and the community structure of the multilayer network is detected by maximizing the modularity of multilayer networks. Finally, we verify the effectiveness of the detection algorithm on synthetic networks. In the experiments on synthetic networks, comparing with the classical community detection algorithms (without considering interlayer heterogeneity), the motif-based modularity community detection algorithm can obtain better results under different evaluation indexes, and we found that there exists a certain relationship between motifs and communities. In addition, the proposed algorithm is applied in the empirical network, which shows its practicability in the real world. This study provides a solution for the investigation of heterogeneous information in multilayer networks.
Field evaluation of a simple and rapid diagnostic test, RLDT to detect Shigella and enterotoxigenic E. coli in Indian children
Authors: Chowdhury Goutam , Ghosh Debjani , Zhou Yiyi , Deb Alok K. , Mukhopadhyay Asish Kumar , Dutta Shanta , Chakraborty Subhra
Published: April 2024

The diagnostic assays currently used to detect Shigella spp. (Shigella) and enterotoxigenic Escherichia coli (ETEC) are complex or elaborate which make them difficult to apply in resource poor settings where these diseases are endemic. The simple and rapid nucleic acid amplification-based assay "Rapid LAMP-based Diagnostic Test (RLDT)" was evaluated to detect Shigella spp (Shigella) and enterotoxigenic Escherichia coli (ETEC) and determine the epidemiology of these pathogens in Kolkata, India. Stool samples (n = 405) from children under five years old with diarrhea seeking care at the hospitals were tested, and 85(21%) and 68(17%) by RLDT, 91(23%) and 58(14%) by quantitative PCR (qPCR) and 35(9%) and 15(4%) by culture, were positive for Shigella and ETEC, respectively. The RLDT showed almost perfect agreement with qPCR, Kappa 0.96 and 0.89; sensitivity 93% and 98%; specificity 100% and 97% for Shigella and ETEC, respectively. While RLDT detected additional 12% Shigella and 13% ETEC than culture, all culture positives for Shigella and ETEC except one each were also positive by the RLDT, sensitivity 97% and 93% respectively. RLDT is a simple, sensitive, and rapid assay that could be implemented with minimum training in the endemic regions to strengthen the disease surveillance system and rapid outbreak detection.
Understanding vegetation phenology responses to easily ignored climate factors in china's mid-high latitudes
Authors: Wang Qianfeng , Chen Huixia , Xu Feng , Bento Virgílio A. , Zhang Rongrong , Wu Xiaoping , Guo Pengcheng
Published: April 2024

Previous studies have primarily focused on the influence of temperature and precipitation on phenology. It is unclear if the easily ignored climate factors with drivers of vegetation growth can effect on vegetation phenology. In this research, we conducted an analysis of the start (SOS) and end (EOS) of the growing seasons in the northern region of China above 30°N from 1982 to 2014, focusing on two-season vegetation phenology. We examined the response of vegetation phenology of different vegetation types to preseason climatic factors, including relative humidity (RH), shortwave radiation (SR), maximum temperature (Tmax), and minimum temperature (Tmin). Our findings reveal that the optimal preseason influencing vegetation phenology length fell within the range of 0–60 days in most areas. Specifically, SOS exhibited a significant negative correlation with Tmax and Tmin in 44.15% and 42.25% of the areas, respectively, while EOS displayed a significant negative correlation with SR in 49.03% of the areas. Additionally, we identified that RH emerged as the dominant climatic factor influencing the phenology of savanna (SA), whereas temperature strongly controlled the SOS of deciduous needleleaf forest (DNF) and deciduous broadleaf forest (DBF). Meanwhile, the EOS of DNF was primarily influenced by Tmax. In conclusion, this study provides valuable insights into how various vegetation types adapt to climate change, offering a scientific basis for implementing effective vegetation adaptation measures.
Predictors of divorce and duration of marriage among first marriage women in Dejne administrative town
Authors: Shita Nigusie Gashaye , Zeleke Liknaw Bewket
Published: April 2024

Divorce is a common occurrence in the marital lives of spouses. Consequently, numerous divorced spouses and their children face various social, economic, physiological, and health problems after breaking their marriage. This study aimed to identify the predictors of divorce and the duration of marriage. We conducted a community-based cross-sectional study among 423 randomly selected residents of Dejen Township in April 2020, of which only 369 respondents met the study inclusion criteria. We used structured questionnaires to collect data. The predictors of divorce and duration of marriage were analyzed using binary logistic regression and the Gompertz regression model, respectively. A p value less than 0.05 was used to express statistical significance. The prevalence of divorce was 21.14% [95% CI (19.01–23.27%)]. Half of these women broke up their marriage after 11 years. A high age difference (7 or more years) between spouses, an early marriage, infertility among women, the presence of third parties, women without formal education, women in the workforce, sexually dissatisfied women, women who did not live together with their husbands at the same address, partner violence, marital control behaviour of husbands, drug-abused husbands, spouses without children, and women who knew multiple sexual partners were the significant predictors of divorce. Partner violence, sexually dissatisfied women, women who made their own marriage decisions, marital control behaviour of husbands, women who did not live together with their husbands at the same address, drug-abused husbands and spouses without children were significant predictors of shorter marriage durations. In this study, the prevalence of divorce was high. Therefore, a community-based, integrated strategy is needed to minimize the divorce rate.
The role of the correlated motion(s) of the chromophore in photoswitching of green and red forms of the photoconvertible fluorescent protein mSAASoti
Authors: Gavshina Alexandra V. , Solovyev Ilya D. , Khrenova Maria G. , Boyko Konstantin M. , Varfolomeeva Larisa A. , Minyaev Mikhail E. , Popov Vladimir O. , Savitsky Alexander P.
Published: April 2024

Wild-type SAASoti and its monomeric variant mSAASoti can undergo phototransformations, including reversible photoswitching of the green form to a nonfluorescent state and irreversible green-to-red photoconversion. In this study, we extend the photochemistry of mSAASoti variants to enable reversible photoswitching of the red form. This result is achieved by rational and site-saturated mutagenesis of the M163 and F177 residues. In the case of mSAASoti it is M163T substitution that leads to the fastest switching and the most photostable variant, and reversible photoswitching can be observed for both green and red forms when expressed in eukaryotic cells. We obtained a 13-fold increase in the switching efficiency with the maximum switching contrast of the green form and the appearance of comparable switching of the red form for the C21N/M163T mSAASoti variant. The crystal structure of the C21N mSAASoti in its green on-state was obtained for the first time at 3.0 Å resolution, and it is in good agreement with previously calculated 3D-model. Dynamic network analysis reveals that efficient photoswitching occurs if motions of the 66H residue and phenyl fragment of chromophore are correlated and these moieties belong to the same community.
Convenient and efficient N-methylation of secondary amines under solvent-free ball milling conditions
Authors: Walter Mikołaj , Ciupak Olga , Biernacki Karol , Rachoń Janusz , Witt Dariusz , Demkowicz Sebastian
Published: April 2024

In the present work, we report the development of a rapid, efficient, and solvent-free procedure for the N-methylation of secondary amines under mechanochemical conditions. After optimization of the milling parameters, a vibrational ball mill was used to synthesize 26 tertiary N-methylated amine derivatives in a short time of 20 min (30 Hz frequency) and high yields ranging from 78 to 95%. An exception was compounds having a hydroxyl group in their structure, for which a decrease in reaction efficiency was observed. During our research, we investigated alternate reaction selectivity occurring in compounds able to form ring closure products that are 3,4-dihydro-2H-1,3-benzoxazine derivatives instead of N-methylated products. The liquid-assisted grinding technique has been applied using formalin as a methylating agent and sodium triacetoxyborohydride as a reducing agent in a reductive amination reaction.
PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis
Authors: Alnuaimi Saif , Reljic Tea , Abdulla Fatima S. , Memon Hamda , Al-Ali Sarah , Smith Teagen , Serdarevic Fadila , Velija Asimi Zelija , Kumar Ambuj , Semiz Sabina
Published: April 2024

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = − 22.07 mg/dl (95% CI − 27.17, − 16.97), HbA1c [MD = − 0.53% (95% CI − 0.67, − 0.38)], HOMA-IR [MD = − 1.26 (95% CI − 2.16, − 0.37)], and fasting insulin [MD = − 19.83 pmol/L (95% CI − 29.54, − 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.

PROSPERO registration no. CRD42023412603.
SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids
Authors: Chau Chiu Wang , To Alex , Au-Yeung Rex K. H. , Tang Kaiming , Xiang Yang , Ruan Degong , Zhang Lanlan , Wong Hera , Zhang Shihui , Au Man Ting , Chung Seok , Song Euijeong , Choi Dong-Hee , Liu Pentao , Yuan Shuofeng , Wen Chunyi , Sugimura Ryohichi
Published: April 2024

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages’ role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.
In silico exploration of phenolics as modulators of penicillin binding protein (PBP) 2× of Streptococcus pneumoniae
Authors: Aribisala Jamiu Olaseni , S’thebe Nosipho Wendy , Sabiu Saheed
Published: April 2024

Infections caused by multidrug-resistant Streptococcus pneumoniae remain the leading cause of pneumonia-related deaths in children < 5 years globally, and mutations in penicillin-binding protein (PBP) 2 × have been identified as the major cause of resistance in the organism to beta-lactams. Thus, the development of new modulators with enhanced binding of PBP2x is highly encouraged. In this study, phenolics, due to their reported antibacterial activities, were screened against the active site of PBP2x using structure-based pharmacophore and molecular docking techniques, and the ability of the top-hit phenolics to inhibit the active and allosteric sites of PBP2x was refined through 120 ns molecular dynamic simulation. Except for gallocatechin gallate and lysidicichin, respectively, at the active and allosteric sites of PBP2x, the top-hit phenolics had higher negative binding free energy (ΔGbind) than amoxicillin [active site (− 19.23 kcal/mol), allosteric site (− 33.75 kcal/mol)]. Although silicristin had the best broad-spectrum effects at the active (− 38.41 kcal/mol) and allosteric (− 50.54 kcal/mol) sites of PBP2x, the high thermodynamic entropy (4.90 Å) of the resulting complex might suggest the need for its possible structural refinement for enhanced potency. Interestingly, silicristin had a predicted synthetic feasibility score of < 5 and quantum calculations using the DFT B3LYP/6-31G+ (dp) revealed that silicristin is less stable and more reactive than amoxicillin. These findings point to the possible benefits of the top-hit phenolics, and most especially silicristin, in the direct and synergistic treatment of infections caused by S. pneumoniae. Accordingly, silicristin is currently the subject of further confirmatory in vitro research.
BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape
Authors: Planchard David , Sanborn Rachel E. , Negrao Marcelo V. , Vaishnavi Aria , Smit Egbert F.
Published: April 2024

In this review, we cover the current understanding of BRAF mutations and associated clinical characteristics in patients with metastatic NSCLC, approved and emerging treatment options, BRAF sequencing approaches, and unmet needs. The BRAFV600E mutation confers constitutive activity of the MAPK pathway, leading to enhanced growth, proliferation, and survival of tumor cells. Testing for BRAF mutations enables patients to be treated with therapies that directly target BRAFV600E and the MAPK pathway, but BRAF testing lags behind other oncogene testing in metastatic NSCLC. Additional therapies targeting BRAFV600E mutations provide options for patients with metastatic NSCLC. Emerging therapies and combinations under investigation could potentially overcome issues of resistance and target non-V600E mutations. Therefore, because targeted therapies with enhanced efficacy are on the horizon, being able to identify BRAF mutations in metastatic NSCLC may become even more important.
The VP53 protein encoded by RNA2 of a fabavirus, broad bean wilt virus 2, is essential for viral systemic infection
Authors: Kim Myung-Hwi , Choi Boram , Jang Seok-Yeong , Choi Ji-Soo , Kim Sora , Lee Yubin , Park Suejin , Kwon Sun-Jung , Kang Jin-Ho , Seo Jang-Kyun
Published: April 2024

Plant viruses evolves diverse strategies to overcome the limitations of their genomic capacity and express multiple proteins, despite the constraints imposed by the host translation system. Broad bean wilt virus 2 (BBWV2) is a widespread viral pathogen, causing severe damage to economically important crops. It is hypothesized that BBWV2 RNA2 possesses two alternative in-frame translation initiation codons, resulting in the production of two largely overlapping proteins, VP53 and VP37. In this study, we aim to investigate the expression and function of VP53, an N-terminally 128-amino-acid-extended form of the viral movement protein VP37, during BBWV2 infection. By engineering various recombinant and mutant constructs of BBWV2 RNA2, here we demonstrate that VP53 is indeed expressed during BBWV2 infection. We also provide evidence of the translation of the two overlapping proteins through ribosomal leaky scanning. Furthermore, our study highlights the indispensability of VP53 for successful systemic infection of BBWV2, as its removal results in the loss of virus infectivity. These insights into the translation mechanism and functional role of VP53 during BBWV2 infection significantly contribute to our understanding of the infection mechanisms employed by fabaviruses.
The role of stacking fault tetrahedra on void swelling in irradiated copper
Authors: Yu Ziang , Lin Yan-Ru , Zachman Michael J. , Zinkle Steven J. , Xu Haixuan
Published: April 2024

A long-standing and critical issue in the field of irradiated structural materials is that void swelling is significantly higher in face-centered cubic-structured (fcc) materials (1% dpa−1) as compared to that of body-centered cubic-structured (bcc) materials (0.2% dpa−1). Despite extensive research in this area, the underlying mechanism of the difference in swelling resistance between these two types of materials is not yet fully understood. Here, by combining atomistic simulations and STEM imaging, we find stacking fault tetrahedra (SFTs) are the primary cause of the high swelling rate in pure fcc copper. We reveal that SFTs in fcc copper are not neutral sinks, different from the conventional knowledge. On the contrary, they are highly biased compared to other types of sinks because of the SFT-point defect interaction mechanism. SFTs show strong absorption of mobile self-interstitial atoms (SIAs) from the faces and vertices, and weak absorption of mobile vacancies from the edges. We compare the predicted swelling rates with experimental findings under varying conditions, demonstrating the distinct contributions of each type of sink. These findings will contribute to understanding the swelling of irradiated structural materials, which may facilitate the design of materials with high swelling resistance.
Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism
Authors: Chen Xiaorui , Luo Yang , Zhu Qing , Zhang Jingzi , Huang Huan , Kan Yansheng , Li Dian , Xu Ming , Liu Shuohan , Li Jianxiao , Pan Jinmeng , Zhang Li , Guo Yan , Wang Binghao , Qi Guantong , Zhou Zhen , Zhang Chen-Yu , Fang Lei , Wang Yanbo , Chen Xi
Published: April 2024

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.
Memory for rewards guides retrieval
Authors: Nagel Juliane , Morgan David Philip , Gürsoy Necati Çağatay , Sander Samuel , Kern Simon , Feld Gordon Benedikt
Published: April 2024

Rewards paid out for successful retrieval motivate the formation of long-term memory. However, it has been argued that the Motivated Learning Task does not measure reward effects on memory strength but decision-making during retrieval. We report three large-scale online experiments in healthy participants (N = 200, N = 205, N = 187) that inform this debate. In experiment 1, we found that explicit stimulus-reward associations formed during encoding influence response strategies at retrieval. In experiment 2, reward affected memory strength and decision-making strategies. In experiment 3, reward affected decision-making strategies only. These data support a theoretical framework that assumes that promised rewards not only increase memory strength, but additionally lead to the formation of stimulus-reward associations that influence decisions at retrieval.
Principles of organelle positioning in motile and non-motile cells
Authors: Kroll Janina , Renkawitz Jörg
Published: April 2024

Cells are equipped with asymmetrically localised and functionally specialised components, including cytoskeletal structures and organelles. Positioning these components to specific intracellular locations in an asymmetric manner is critical for their functionality and affects processes like immune responses, tissue maintenance, muscle functionality, and neurobiology. Here, we provide an overview of strategies to actively move, position, and anchor organelles to specific locations. By conceptualizing the cytoskeletal forces and the organelle-to-cytoskeleton connectivity, we present a framework of active positioning of both membrane-enclosed and membrane-less organelles. Using this framework, we discuss how different principles of force generation and organelle anchorage are utilised by different cells, such as mesenchymal and amoeboid cells, and how the microenvironment influences the plasticity of organelle positioning. Given that motile cells face the challenge of coordinating the positioning of their content with cellular motion, we particularly focus on principles of organelle positioning during migration. In this context, we discuss novel findings on organelle positioning by anchorage-independent mechanisms and their advantages and disadvantages in motile as well as stationary cells.
Efforts to promote osteogenesis–angiogenesis coupling for bone tissue engineering
Authors: Xu Zhiwei , Wang Bingbing , Huang Ruoyu , Guo Mengyao , Han Di , Yin Lan , Zhang Xiaoyun , Huang Yong , Li Xiaoming
Published: April 2024

The current efforts to ameliorate the coupling of osteogenesis and angiogenesis were summarized comprehensively and explored in depth from the optimization strategies of scaffolds to the employment tricks for bioactive substances and cells.
Anodic voltage performance of conducting polymer-functionalized boron nitride nanosheets: a DFT assessment
Authors: Nnadiekwe Chidera C. , Sajid Hasnain , Abdulazeez Ismail , Al-Saadi Abdulaziz A.
Published: April 2024

Manipulating electronic features of boron nitride nanosheets through non-covalent functionalization using conducting polymers shall boost the cell voltage output.
Milk-derived Lactobacillus with high production of short-chain fatty acids relieves antibiotic-induced diarrhea in mice
Authors: Xu Baofeng , Wang Zengbo , Wang Yuqi , Zhang Kangyong , Li Jian , Zhou Linyi , Li Bailiang
Published: April 2024

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, and this has warranted research into alternative protocols.
High-precision measurement of Ag isotopes for silicate rocks by MC-ICP-MS
Authors: Fang Yuan , Wen Qiu-Yu , Xiao Zi-Cong , Yu Hui-Min , Huang Fang
Published: April 2024

A new protocol for the high-precision measurement of Ag isotopes for samples with low Ag contents by MC-ICP-MS.
Unveiling sultam in drug discovery: spotlight on the underexplored scaffold
Authors: Chong Yie Kie , Ong Yee Swen , Yeong Keng Yoon
Published: April 2024

The sulfonamide scaffold is widely applied in drug discovery. In recent years, there has been growing investigation on cyclic sulfonamides (sultams) as they offer much potential in combating various diseases.
Effect of equilibration time on the structural gradient in the vertical direction for bicontinuous microemulsions in Winsor-III and -IV systems
Authors: Hayes Douglas G. , Barth Brian A. , Pingali Sai Venkatesh
Published: April 2024

Both equilibration time and the transfer of Winsor-III microemulsion systems from one container to another affect the structure of the bicontinuous phase in the vertical direction.
Aggregation of oligomeric Ir photosensitizers promotes efficient and long-lifetime photocatalytic hydrogen evolution
Authors: Huang Yifan , Liu Shihan , Wang Bo , Wang Ying , Zhang Yifan , Deng Pengyang
Published: April 2024

This work first reports the aggregation effect of Ir oligomeric photosensitizers, which provides extra intermolecular electron transfer path and leads to a high photocatalytic hydrogen evolution activity and a long lifetime of the photosensitizers.
A new versatile crystalline sponge for organic structural analysis without the need for activation
Authors: Liu Jin-Chang , Huang Wei-Ping , Tian Yu-Xin , Xu Wei , Ye Wen-Cai , Jiang Ren-Wang
Published: April 2024

A new carbazole metal organic framework (CMOF) was synthesized as a new versatile crystalline sponge for organic structural analysis without the need for activation.
Rapid in situ growth of high-entropy oxide nanoparticles with reversible spinel structures for efficient Li storage
Authors: Zhu Siyu , Nong Wei , Nicholas Lim Jun Ji , Cao Xun , Zhang Peilin , Lu Yu , Xiu Mingzhen , Huang Kang , Wu Gang , Yang Shuo-Wang , Wu Junsheng , Liu Zheng , Srinivasan Madhavi , Hippalgaonkar Kedar , Huang Yizhong
Published: April 2024

Using laser radiation, high-entropy nanoparticles were rapidly fabricated on conductive carbon. The high-entropy nanomaterials with reversible spinel structures exhibit better cycling and rate performances in LIBs.
Assessment of urine sample collection and processing variables for extracellular vesicle-based proteomics
Authors: Zhang Guiyuan , Ding Yajie , Zhang Hao , Wei Dong , Liu Yufeng , Sun Jie , Xie Zhuoying , Tao W. Andy , Zhu Yefei
Published: April 2024

Extracellular vesicles (EVs) in urine are a promising source for developing non-invasive biomarkers.