bluuebunny/crossref_metadata_2025 huggingface dataset:
Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression
Authors: Lee Yeajina , Chowdhury Tamrin , Kim Sojin , Yu Hyeon Jong , Kim Kyung-Min , Kang Ho , Kim Min-Sung , Kim Jin Wook , Kim Yong-Hwy , Ji So Young , Hwang Kihwan , Han Jung Ho , Hwang Jinha , Yoo Seong-Keun , Lee Kyu Sang , Choe Gheeyoung , Won Jae-Kyung , Park Sung-Hye , Lee Yong Kyu , Shin Joo Heon , Park Chul-Kee , Kim Chae-Yong , Kim Jong-Il
Published: April 2024

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.
Very long wave infrared quantum dot photodetector up to 18 μm
Authors: Xue Xiaomeng , Hao Qun , Chen Menglu
Published: April 2024

Colloidal quantum dots (CQDs) are of interest for optoelectronic devices because of the possibility of high-throughput solution processing and the wide energy gap tunability from ultraviolet to infrared wavelengths. People may question about the upper limit on the CQD wavelength region. To date, although the CQD absorption already reaches terahertz, the practical photodetection wavelength is limited within mid-wave infrared. To figure out challenges on CQD photoresponse in longer wavelength, would reveal the ultimate property on these nanomaterials. What’s more, it motivates interest in bottom-up infrared photodetection with less than 10% cost compared with epitaxial growth semiconductor bulk. In this work, developing a re-growth method and ionic doping modification, we demonstrate photodetection up to 18 μm wavelength on HgTe CQD. At liquid nitrogen temperature, the responsivity reaches 0.3 A/W and 0.13 A/W, with specific detectivity 6.6 × 108 Jones and 2.3 × 109 Jones for 18 μm and 10 μm CQD photoconductors, respectively. This work is a step toward answering the general question on the CQD photodetection wavelength limitation.
Endothelial DR6 in blood-brain barrier malfunction in Alzheimer’s disease
Authors: Huang Xiaomin , Qi Junhua , Su Yixun , Zhou Ying , Wang Qi , Huang Taida , Xue Dongdong , Zeng Yunxin , Verkhratsky Alexei , Zhou Benjie , Chen Hui , Yi Chenju
Published: April 2024

The impairment of the blood-brain barrier (BBB) has been increasingly recognised as a critical element in the early pathogenesis of Alzheimer’s disease (AD), prompting a focus on brain endothelial cells (BECs), which serve as the primary constituents of the BBB. Death receptor 6 (DR6) is highly expressed in brain vasculature and acts downstream of the Wnt/β-catenin pathway to promote BBB formation during development. Here, we found that brain endothelial DR6 levels were significantly reduced in a murine model of AD (APPswe/PS1dE9 mice) at the onset of amyloid-β (Aβ) accumulation. Toxic Aβ25-35 oligomer treatment recapitulated the reduced DR6 in cultured BECs. We further showed that suppressing DR6 resulted in BBB malfunction in the presence of Aβ25-35 oligomers. In contrast, overexpressing DR6 increased the level of BBB functional proteins through the activation of the Wnt/β-catenin and JNK pathways. More importantly, DR6 overexpression in BECs was sufficient to rescue BBB dysfunction in vitro. In conclusion, our findings provide new insight into the role of endothelial DR6 in AD pathogenesis, highlighting its potential as a therapeutic target to tackle BBB dysfunction in early-stage AD progression.
Growth of millimeter-sized 2D metal iodide crystals induced by ion-specific preference at water-air interfaces
Authors: Zhong Jingxian , Zhou Dawei , Bai Qi , Liu Chao , Fan Xinlian , Zhang Hehe , Li Congzhou , Jiang Ran , Zhao Peiyi , Yuan Jiaxiao , Li Xiaojiao , Zhan Guixiang , Yang Hongyu , Liu Jing , Song Xuefen , Zhang Junran , Huang Xiao , Zhu Chao , Zhu Chongqin , Wang Lin
Published: April 2024

Conventional liquid-phase methods lack precise control in synthesizing and processing materials with macroscopic sizes and atomic thicknesses. Water interfaces are ubiquitous and unique in catalyzing many chemical reactions. However, investigations on two-dimensional (2D) materials related to water interfaces remain limited. Here we report the growth of millimeter-sized 2D PbI2 single crystals at the water-air interface. The growth mechanism is based on an inherent ion-specific preference, i.e. iodine and lead ions tend to remain at the water-air interface and in bulk water, respectively. The spontaneous accumulation and in-plane arrangement within the 2D crystal of iodide ions at the water-air interface leads to the unique crystallization of PbI2 as well as other metal iodides. In particular, PbI2 crystals can be customized to specific thicknesses and further transformed into millimeter-sized mono- to few-layer perovskites. Additionally, we have developed water-based techniques, including water-soaking, spin-coating, water-etching, and water-flow-assisted transfer to recycle, thin, pattern, and position PbI2, and subsequently, perovskites. Our water-interface mediated synthesis and processing methods represents a significant advancement in achieving simple, cost-effective, and energy-efficient production of functional materials and their integrated devices.
A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules
Authors: Reed Kevin B. , Brooks Sierra M. , Wells Jordan , Blake Kristin J. , Zhao Minye , Placido Kira , d’Oelsnitz Simon , Trivedi Adit , Gadhiyar Shruti , Alper Hal S.
Published: April 2024

Halogen-containing molecules are ubiquitous in modern society and present unique chemical possibilities. As a whole, de novo fermentation and synthetic pathway construction for these molecules remain relatively underexplored and could unlock molecules with exciting new applications in industries ranging from textiles to agrochemicals to pharmaceuticals. Here, we report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in Escherichia coli from glucose. First, we engineer E. coli to produce between 300 and 700 mg/L of six different halogenated tryptophan precursors. Second, we harness the native promiscuity of multiple downstream enzymes to access unexplored regions of metabolism. Finally, through modular co-culture fermentations, we demonstrate a plug-and-play bioproduction platform, culminating in the generation of 26 distinct halogenated molecules produced de novo including precursors to prodrugs 4-chloro- and 4-bromo-kynurenine and new-to-nature halogenated beta carbolines.
Unveiling unique microbial nitrogen cycling and nitrification driver in coastal Antarctica
Authors: Han Ping , Tang Xiufeng , Koch Hanna , Dong Xiyang , Hou Lijun , Wang Danhe , Zhao Qian , Li Zhe , Liu Min , Lücker Sebastian , Shi Guitao
Published: April 2024

Largely removed from anthropogenic delivery of nitrogen (N), Antarctica has notably low levels of nitrogen. Though our understanding of biological sources of ammonia have been elucidated, the microbial drivers of nitrate (NO3−) cycling in coastal Antarctica remains poorly understood. Here, we explore microbial N cycling in coastal Antarctica, unraveling the biological origin of NO3− via oxygen isotopes in soil and lake sediment, and through the reconstruction of 1968 metagenome-assembled genomes from 29 microbial phyla. Our analysis reveals the metabolic potential for microbial N2 fixation, nitrification, and denitrification, but not for anaerobic ammonium oxidation, signifying a unique microbial N-cycling dynamic. We identify the predominance of complete ammonia oxidizing (comammox) Nitrospira, capable of performing the entire nitrification process. Their adaptive strategies to the Antarctic environment likely include synthesis of trehalose for cold stress, high substrate affinity for resource utilization, and alternate metabolic pathways for nutrient-scarce conditions. We confirm the significant role of comammox Nitrospira in the autotrophic, nitrification process via 13C-DNA-based stable isotope probing. This research highlights the crucial contribution of nitrification to the N budget in coastal Antarctica, identifying comammox Nitrospira clade B as a nitrification driver.
Diverse and abundant phages exploit conjugative plasmids
Authors: Quinones-Olvera Natalia , Owen Siân V. , McCully Lucy M. , Marin Maximillian G. , Rand Eleanor A. , Fan Alice C. , Martins Dosumu Oluremi J. , Paul Kay , Sanchez Castaño Cleotilde E. , Petherbridge Rachel , Paull Jillian S. , Baym Michael
Published: April 2024

Phages exert profound evolutionary pressure on bacteria by interacting with receptors on the cell surface to initiate infection. While the majority of phages use chromosomally encoded cell surface structures as receptors, plasmid-dependent phages exploit plasmid-encoded conjugation proteins, making their host range dependent on horizontal transfer of the plasmid. Despite their unique biology and biotechnological significance, only a small number of plasmid-dependent phages have been characterized. Here we systematically search for new plasmid-dependent phages targeting IncP and IncF plasmids using a targeted discovery platform, and find that they are common and abundant in wastewater, and largely unexplored in terms of their genetic diversity. Plasmid-dependent phages are enriched in non-canonical types of phages, and all but one of the 65 phages we isolated were non-tailed, and members of the lipid-containing tectiviruses, ssDNA filamentous phages or ssRNA phages. We show that plasmid-dependent tectiviruses exhibit profound differences in their host range which is associated with variation in the phage holin protein. Despite their relatively high abundance in wastewater, plasmid-dependent tectiviruses are missed by metaviromic analyses, underscoring the continued importance of culture-based phage discovery. Finally, we identify a tailed phage dependent on the IncF plasmid, and find related structural genes in phages that use the orthogonal type 4 pilus as a receptor, highlighting the evolutionarily promiscuous use of these distinct contractile structures by multiple groups of phages. Taken together, these results indicate plasmid-dependent phages play an under-appreciated evolutionary role in constraining horizontal gene transfer via conjugative plasmids.
Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells
Authors: Barnkob Mike B. , Michaels Yale S. , André Violaine , Macklin Philip S. , Gileadi Uzi , Valvo Salvatore , Rei Margarida , Kulicke Corinna , Chen Ji-Li , Jain Vitul , Woodcock Victoria K. , Colin-York Huw , Hadjinicolaou Andreas V. , Kong Youxin , Mayya Viveka , Mazet Julie M. , Mead Gracie-Jennah , Bull Joshua A. , Rijal Pramila , Pugh Christopher W. , Townsend Alain R. , Gérard Audrey , Olsen Lars R. , Fritzsche Marco , Fulga Tudor A. , Dustin Michael L. , Jones E. Yvonne , Cerundolo Vincenzo
Published: April 2024

Semaphorin-3A (SEMA3A) functions as a chemorepulsive signal during development and can affect T cells by altering their filamentous actin (F-actin) cytoskeleton. The exact extent of these effects on tumour-specific T cells are not completely understood. Here we demonstrate that Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 are upregulated on stimulated CD8+ T cells, allowing tumour-derived SEMA3A to inhibit T cell migration and assembly of the immunological synapse. Deletion of NRP1 in both CD4+ and CD8+ T cells enhance CD8+ T-cell infiltration into tumours and restricted tumour growth in animal models. Conversely, over-expression of SEMA3A inhibit CD8+ T-cell infiltration. We further show that SEMA3A affects CD8+ T cell F-actin, leading to inhibition of immune synapse formation and motility. Examining a clear cell renal cell carcinoma patient cohort, we find that SEMA3A expression is associated with reduced survival, and that T-cells appear trapped in SEMA3A rich regions. Our study establishes SEMA3A as an inhibitor of effector CD8+ T cell tumour infiltration, suggesting that blocking NRP1 could improve T cell function in tumours.
Bright, efficient, and stable pure-green hyperfluorescent organic light-emitting diodes by judicious molecular design
Authors: Lee Yi-Ting , Chan Chin-Yiu , Matsuno Nanami , Uemura Shigetada , Oda Susumu , Kondo Masakazu , Weerasinghe Rangani Wathsala , Hu Yanmei , Lestanto Gerardus N. Iswara , Tsuchiya Youichi , Li Yufang , Hatakeyama Takuji , Adachi Chihaya
Published: April 2024

To fulfill ultra-high-definition display, efficient and bright green organic light-emitting diodes with Commission Internationale de l’Éclairage y-coordinate ≥ 0.7 are required. Although there are some preceding reports of highly efficient devices based on pure-green multi-resonance emitters, the efficiency rolloff and device stabilities for those pure-green devices are still unsatisfactory. Herein, we report the rational design of two pure-green multi-resonance emitters for achieving highly stable and efficient pure-green devices with CIEx,ys that are close to the NTSC and BT. 2020 standards. In this study, our thermally activated delayed fluorescence OLEDs based on two pure-green multi-resonance emitters result in CIEy up to 0.74. In hyperfluorescent device architecture, the CIExs further meet the x-coordinate requirements, i.e., NTSC (0.21) and BT. 2020 (0.17), while keeping their CIEys ~ 0.7. Most importantly, hyperfluorescent devices display the high maximum external quantum efficiencies of over 25% and maximum luminance of over 105 cd m−2 with suppressed rolloffs (external quantum efficiency of ~20% at 104 cd m−2) and long device stabilities with LT95s of ~ 600 h.
Stimulus encoding by specific inactivation of cortical neurons
Authors: Pérez-Ortega Jesús , Akrouh Alejandro , Yuste Rafael
Published: April 2024

Neuronal ensembles are groups of neurons with correlated activity associated with sensory, motor, and behavioral functions. To explore how ensembles encode information, we investigated responses of visual cortical neurons in awake mice using volumetric two-photon calcium imaging during visual stimulation. We identified neuronal ensembles employing an unsupervised model-free algorithm and, besides neurons activated by the visual stimulus (termed “onsemble”), we also find neurons that are specifically inactivated (termed “offsemble”). Offsemble neurons showed faster calcium decay during stimuli, suggesting selective inhibition. In response to visual stimuli, each ensemble (onsemble+offsemble) exhibited small trial-to-trial variability, high orientation selectivity, and superior predictive accuracy for visual stimulus orientation, surpassing the sum of individual neuron activity. Thus, the combined selective activation and inactivation of cortical neurons enhances visual encoding as an emergent and distributed neural code.
Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control
Authors: Bange Manuel , Gonzalez-Escamilla Gabriel , Herz Damian M. , Tinkhauser Gerd , Glaser Martin , Ciolac Dumitru , Pogosyan Alek , Kreis Svenja L. , Luhmann Heiko J. , Tan Huiling , Groppa Sergiu
Published: April 2024

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson’s disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson’s disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson’s disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.
Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial
Authors: Yarchoan Mark , Gane Edward J. , Marron Thomas U. , Perales-Linares Renzo , Yan Jian , Cooch Neil , Shu Daniel H. , Fertig Elana J. , Kagohara Luciane T. , Bartha Gabor , Northcott Josette , Lyle John , Rochestie Sarah , Peters Joann , Connor Jason T. , Jaffee Elizabeth M. , Csiki Ildiko , Weiner David B. , Perales-Puchalt Alfredo , Sardesai Niranjan Y.
Published: April 2024

Programmed cell death protein 1 (PD-1) inhibitors have modest efficacy as a monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 inhibitors through the induction of tumor-specific immunity. We present results from a single-arm, open-label, phase 1/2 study of a DNA plasmid PTCV (GNOS-PV02) encoding up to 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab in patients with advanced HCC previously treated with a multityrosine kinase inhibitor. Safety and immunogenicity were assessed as primary endpoints, and treatment efficacy and feasibility were evaluated as secondary endpoints. The most common treatment-related adverse events were injection-site reactions, observed in 15 of 36 (41.6%) patients. No dose-limiting toxicities or treatment-related grade ≥3 events were observed. The objective response rate (modified intention-to-treat) per Response Evaluation Criteria in Solid Tumors 1.1 was 30.6% (11 of 36 patients), with 8.3% (3 of 36) of patients achieving a complete response. Clinical responses were associated with the number of neoantigens encoded in the vaccine. Neoantigen-specific T cell responses were confirmed in 19 of 22 (86.4%) evaluable patients by enzyme-linked immunosorbent spot assays. Multiparametric cellular profiling revealed active, proliferative and cytolytic vaccine-specific CD4+ and CD8+ effector T cells. T cell receptor β-chain (TCRβ) bulk sequencing results demonstrated vaccination-enriched T cell clone expansion and tumor infiltration. Single-cell analysis revealed posttreatment T cell clonal expansion of cytotoxic T cell phenotypes. TCR complementarity-determining region cloning of expanded T cell clones in the tumors following vaccination confirmed reactivity against vaccine-encoded neoantigens. Our results support the PTCV’s mechanism of action based on the induction of antitumor T cells and show that a PTCV plus pembrolizumab has clinical activity in advanced HCC. ClinicalTrials.gov identifier: NCT04251117.
Possible involvement of zinc transporter ZIP13 in myogenic differentiation
Authors: Shoji Masaki , Ohashi Takuto , Nagase Saki , Yuri Haato , Ichihashi Kenta , Takagishi Teruhisa , Nagata Yuji , Nomura Yuki , Fukunaka Ayako , Kenjou Sae , Miyake Hatsuna , Hara Takafumi , Yoshigai Emi , Fujitani Yoshio , Sakurai Hidetoshi , dos Santos Heloísa G. , Fukada Toshiyuki , Kuzuhara Takashi
Published: April 2024

Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13G64D) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.
Isolation and propagation of an Egyptian Theileria annulata infected cell line and evaluation of its use as a vaccine to protect cattle against field challenge
Authors: AL-Hosary Amira , Radwan Ahmed M. , Ahmed Laila S. , Abdelghaffar Sary Kh. , Fischer Susanne , Nijhof Ard M. , Clausen Peter-Henning , Ahmed Jabbar S.
Published: April 2024

Tropical theileriosis is an important protozoan tick-borne disease in cattle. Vaccination using attenuated schizont-infected cell lines is one of the methods used for controlling the disease. This study describes the production of attenuated schizont-infected cell lines from Egypt and an evaluation of its use as a vaccine to protect calves against clinical disease upon field challenge. Two groups of exotic and crossbred male calves were divided into vaccinated and control groups. The vaccinated groups were inoculated with 4 ml (1 × 106 cells/ml) of the attenuated cell line. Three weeks after vaccination, calves of both groups were transported to the New Valley Governorate (Egyptian oasis) where they were kept under field conditions and exposed to the natural Theileria annulata challenge. All animals in the control group showed severe clinical signs and died despite treatment with buparvaquone, which was administered after two days of persistent fever due to a severe drop in packed cell volume (PCV). Animals in the vaccinated group became seropositive without developing severe clinical signs other than transient fever. Post-mortem examinations revealed enlarged and fragile lymph nodes, spleen, and liver with necrosis and hemorrhages. These findings indicate that the Egyptian attenuated cell line was successful in protecting both exotic and crossbred animals against tropical theileriosis under field conditions.
Porous sulfur polymers for effective aqueous-phase organic contaminant removal
Authors: Diniz Vinicius , Bear Joseph C. , Rath Susanne , Crick Colin R.
Published: April 2024

Sulfur polymers produced through 'inverse vulcanization' exhibit various attributes, such as photocatalytic activity and a high capacity to adsorb heavy metals. Nevertheless, there is a lack of research investigating the use of sulfur polymers as materials for the removal of organic contaminants. In this work, porous sulfur polymers (PSPs) were synthesized from elemental sulfur and 1,3-diisopropenylbenzene, with porosity introduced via salt templating. The result is a material that can strongly adsorb and chemically neutralize a model organic contaminant (caffeine). PSPs show adsorption up to 5 times higher than a leading adsorption material (activated carbon). Furthermore, either the adsorption or degradation processes can govern the removal efficiency depending on the synthesis parameters of PSPs. This is the first-ever report demonstrating sulfur polymers as effective materials for removing emerging contaminants from water. The versatile synthesis of sulfur polymers offers variation, which means that there is much more to explore in this exciting research area.
Quantum biochemical analysis of the TtgR regulator and effectors
Authors: de Carvalho Matias E. G. , Bezerra K. S. , Costa A. H. Lima , Clemente Junior W. S. , Oliveira J. I. N. , Ribeiro Junior L. A. , Galvão D. S. , Fulco U. L.
Published: April 2024

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.
A comprehensive investigation of Bi2O3 on the physical, structural, optical, and electrical properties of K2O.ZnO.V2O5.B2O3 glasses
Authors: Ibrahim S. , Ali A. A. , Fathi Ahlam M.
Published: April 2024

The multi-component glass system has a composition of 10K2O–10ZnO–55 B2O3–(25–x)V2O5–xBi2O3 (x = 4, 5, 7.5, 9, 10 mol%) are synthesized by the melt-quenching method. Using X-ray diffraction examination, the amorphous phase in the material was confirmed. The physical characteristics of the produced compositions are examined using density (D) and molar volume (Vm). Calculations of physical properties showed that adding Bi2O3 from 4 to 10 mol% increased the glass density from 2.7878 to 3.3617 g cm−3 and decreased the molar volume from 40.4196 to 38.5895 cm3/mol. Studies of glass samples using the FTIR show bands of absorption for oxides in different structural groups. Octahedral [$${{\text{BiO}}}_{6}$$

BiO
6

], [$${{\text{BO}}}_{4}$$

BO
4

], and tetrahedral [$${{\text{BO}}}_{3}$$

BO
3

] structural units are observed in the present glass matrices. The cutoff wavelength ($${\lambda }_{C}$$

λ
C

), and optical band gap energy were determined using UV absorption spectra. The increase in non-bridging oxygens can be linked to the decrease in optical band gap energy ($${E}_{opt}$$

E

opt

) (direct and indirect) and the increase in cutoff wavelength with an increase in Bi2O3 content. This is attributed to the existence of bismuth ions and the creation of non-bridging oxygens. Besides that, the values of optical parameters, viz., optical electronegativity, refractive index, and molar refractivity, are calculated. The metallization criterion values are less than 1 and the glass samples exhibit an increased tendency towards metallization. Both the conductivity and the dielectric constant increase with the rise in Bi2O3 content, however, the dielectric loss and the impedance reduce. The behavior and values of conductivity for the studied glasses reveal the semiconducting properties of all glass samples. These results suggest that the produced glass samples may be employed as amorphous semiconductors in electronics and memory switching devices.
Continuous mowing differentially affects floral defenses in the noxious and invasive weed Solanum elaeagnifolium in its native range
Authors: Vasquez Alejandro , Alaniz Alexa , Dearth Robert , Kariyat Rupesh
Published: April 2024

In weeds, disturbance has been found to affect life history traits and mediate trophic interactions. In urban landscapes, mowing is an important disturbance, and we previously showed that continuous mowing leads to enhanced fitness and defense traits in Solanum elaeagnifolium, Silverleaf Nightshade (SLN). However, most studies have been focused on foliar defenses, ignoring floral defenses. In this study we examined whether continuous mowing affected floral defenses in SLN using mowed and unmowed populations in South Texas, their native range. We found flowers of mowed SLN plants larger but lighter than unmowed plants. Additionally, flowers on plants that were mowed frequently were both heavier and larger. Mowed plants had higher spine density and consequently unmowed flowers had higher herbivore damage. Additionally, early instar Manduca sexta fed on mowed flower-based artificial diets showed no difference in mass than the control and unmowed; however, later instars caterpillars on unmowed diets gained significantly more mass than the mowed treatment and control. Mowed plants had higher spine density which may shed light on why unmowed flowers experienced higher herbivore damage. We found caterpillars fed on high mowing frequency diets were heavier than those on low mowing frequency diets. Collectively, we show that mowing compromises floral traits and enhances plant defenses against herbivores and should be accounted for in management.
GIS-based intelligent planning approach of child-friendly pedestrian pathway to promote a child-friendly city
Authors: Fang Kailun , Azizan Suzana Ariff , Huang Huiming
Published: April 2024

Pedestrian safety, particularly for children, relies on well-designed pathways. Child-friendly pathways play a crucial role in safeguarding young pedestrians. Shared spaces accommodating both vehicles and walkers can bring benefits to pedestrians. However, active children playing near these pathways are prone to accidents. This research aims to develop an efficient method for planning child-friendly pedestrian pathways, taking into account community development and the specific needs of children. A mixed-methods approach was employed, utilizing the Datang community in Guangzhou, China, as a case study. This approach combined drawing techniques with GIS data analysis. Drawing methods were utilized to identify points of interest for children aged 2–6. The qualitative and quantitative fuzzy analytic hierarchy process assessed factors influencing pathway planning, assigning appropriate weights. The weighted superposition analysis method constructed a comprehensive cost grid, considering various community elements. To streamline the planning process, a GIS tool was developed based on the identified factors, resulting in a practical, child-friendly pedestrian pathway network. Results indicate that this method efficiently creates child-friendly pathways, ensuring optimal connectivity within the planned road network.
A study on expression recognition based on improved mobilenetV2 network
Authors: Zhu Qiming , Zhuang Hongwei , Zhao Mi , Xu Shuangchao , Meng Rui
Published: April 2024

This paper proposes an improved strategy for the MobileNetV2 neural network(I-MobileNetV2) in response to problems such as large parameter quantities in existing deep convolutional neural networks and the shortcomings of the lightweight neural network MobileNetV2 such as easy loss of feature information, poor real-time performance, and low accuracy rate in facial emotion recognition tasks. The network inherits the characteristics of MobilenetV2 depthwise separated convolution, signifying a reduction in computational load while maintaining a lightweight profile. It utilizes a reverse fusion mechanism to retain negative features, which makes the information less likely to be lost. The SELU activation function is used to replace the RELU6 activation function to avoid gradient vanishing. Meanwhile, to improve the feature recognition capability, the channel attention mechanism (Squeeze-and-Excitation Networks (SE-Net)) is integrated into the MobilenetV2 network. Experiments conducted on the facial expression datasets FER2013 and CK + showed that the proposed network model achieved facial expression recognition accuracies of 68.62% and 95.96%, improving upon the MobileNetV2 model by 0.72% and 6.14% respectively, and the parameter count decreased by 83.8%. These results empirically verify the effectiveness of the improvements made to the network model.
Visualisation of gene expression within the context of tissues using an X-ray computed tomography-based multimodal approach
Authors: Kairišs Kristaps , Sokolova Natalia , Zilova Lucie , Schlagheck Christina , Reinhardt Robert , Baumbach Tilo , Faragó Tomáš , van de Kamp Thomas , Wittbrodt Joachim , Weinhardt Venera
Published: April 2024

The development of an organism is orchestrated by the spatial and temporal expression of genes. Accurate visualisation of gene expression patterns in the context of the surrounding tissues offers a glimpse into the mechanisms that drive morphogenesis. We developed correlative light-sheet fluorescence microscopy and X-ray computed tomography approach to map gene expression patterns to the whole organism`s 3D anatomy. We show that this multimodal approach is applicable to gene expression visualized by protein-specific antibodies and fluorescence RNA in situ hybridisation offering a detailed understanding of individual phenotypic variations in model organisms. Furthermore, the approach offers a unique possibility to identify tissues together with their 3D cellular and molecular composition in anatomically less-defined in vitro models, such as organoids. We anticipate that the visual and quantitative insights into the 3D distribution of gene expression within tissue architecture, by multimodal approach developed here, will be equally valuable for reference atlases of model organisms development, as well as for comprehensive screens, and morphogenesis studies of in vitro models.
Adenosine triphosphate induces amorphous aggregation of amyloid β by increasing Aβ dynamics
Authors: Kuramochi Masahiro , Nakamura Momoka , Takahashi Hiroto , Komoriya Tomoe , Takita Teisuke , Pham Ngan Thi Kim , Yasukawa Kiyoshi , Yoshimune Kazuaki
Published: April 2024

Amyloid β (Aβ) aggregates into two distinct fibril and amorphous forms in the brains of patients with Alzheimer’s disease. Adenosine triphosphate (ATP) is a biological hydrotrope that causes Aβ to form amorphous aggregates and inhibit fibril formation at physiological concentrations. Based on diffracted X-ray blinking (DXB) analysis, the dynamics of Aβ significantly increased immediately after ATP was added compared to those in the absence and presence of ADP and AMP, and the effect diminished after 30 min as the aggregates formed. In the presence of ATP, the β-sheet content of Aβ gradually increased from the beginning, and in the absence of ATP, the content increased rapidly after 180 min incubation, as revealed by a time-dependent thioflavin T fluorescence assay. Images of an atomic force microscope revealed that ATP induces the formation of amorphous aggregates with an average diameter of less than 100 nm, preventing fibrillar formation during 4 days of incubation at 37 °C. ATP may induce amorphous aggregation by increasing the dynamics of Aβ, and as a result, the other aggregation pathway is omitted. Our results also suggest that DXB analysis is a useful method to evaluate the inhibitory effect of fibrillar formation.
Systematic analyses of the factors influencing sperm quality in patients with SARS-CoV-2 infection
Authors: Zhang Guohui , Zhi Weiwei , Ye Fei , Xiong Dongsheng , Zhang Yanan , Liu Fulin , Zhao Yuhong , Du Xinrong , Wu Yang , Hou Mingxia , Liu Jiu , Wei Jiajing , Silang Yangzhong , Xu Wenming , Zeng Jiuzhi , Chen Shiqi , Liu Weixin
Published: April 2024

To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.
CD74 as a prognostic and M1 macrophage infiltration marker in a comprehensive pan-cancer analysis
Authors: Li Ruo Qi , Yan Lei , Zhang Ling , Zhao Yanli , Lian Jing
Published: April 2024

CD74 is a type-II transmembrane glycoprotein that has been linked to tumorigenesis. However, this association was based only on phenotypic studies, and, to date, no in-depth mechanistic studies have been conducted. In this study, combined with a multi-omics study, CD74 levels were significantly upregulated in most cancers relative to normal tissues and were found to be predictive of prognosis. Elevated CD74 expression was associated with reduced levels of mismatch-repair genes and homologous repair gene signatures in over 10 tumor types. Multiple fluorescence staining and bulk, spatial, single-cell transcriptional analyses indicated its potential as a marker for M1 macrophage infiltration in pan-cancer. In addition, CD74 expression was higher in BRCA patients responsive to conventional chemotherapy and was able to predict the prognosis of these patients. Potential CD74-activating drugs (HNHA and BRD-K55186349) were identified through molecular docking to CD74. The findings indicate activation of CD74 may have potential in tumor immunotherapy.
Characteristics and optical properties of atmospheric aerosols based on long-term AERONET investigations in an urban environment of Pakistan
Authors: Zeb Bahadar , Alam Khan , Khan Rehana , Ditta Allah , Iqbal Rashid , Elsadek Mohamed Farouk , Raza Ahsan , Elshikh Mohamed Soliman
Published: April 2024

Radiative balance, local climate, and human health are all significantly influenced by aerosol. Recent severe air pollution over Lahore, a city in Pakistan calls for more thorough research to determine the negative impacts brought on by too many aerosols. To study regional aerosol characteristics and their differences from various aspects, in-depth and long-term (2007–2020) investigations of the columnar aerosol properties over the urban environment of Lahore were carried out by using AERONET data. The Aerosol Optical Depth (AOD400) and Angstrom Exponent (AE400–870) vary from low values of 0.10 to a maximum value of 4.51 and from 0.03 to 1.81, respectively. The huge differences in the amount of AOD440 as well as AE440–870 show the large fluctuation of aerosol classes because of various sources of their emission. During the autumn and winter seasons, the decreasing trend of the optical parameters of aerosols like Single Scattering Albedo (SSA) and Asymmetry Parameter (ASY) with increasing wavelength from 675 to 1020 nm indicates the dominance of light-absorbing aerosols (biomass burning (BB) and industrial/urban (UI). Due to the long-distance dust movement during spring, summer, and autumn, coarse mode particles predominated in Lahore during the study period. Dust type (DD) aerosols are found to be the dominant one during spring (46.92%), summer (54.31%), and autumn (57.46%) while urban industry (BB/UI) was dominant during the winter season (53.21%). During each season, the clean continental (CC) aerosols are found to be in negligible amounts, indicating terrible air quality in Lahore City. The present research work fills up the study gap in the optical properties of aerosols in Lahore and will help us understand more fully how local aerosol fluctuation affects regional climate change over the urban environment of Lahore.
Development of a high throughput system to screen compounds that revert the activated hepatic stellate cells to a quiescent-like state
Authors: Nakano Yasuhiro , Saijou Eiko , Itoh Tohru , Tanaka Minoru , Miyajima Atsushi , Kido Taketomo
Published: April 2024

Chronic liver injury induces fibrosis that often proceeds to cirrhosis and hepatocellular carcinoma, indicating that prevention and/or resolution of fibrosis is a promising therapeutic target. Hepatic stellate cells (HSCs) are the major driver of fibrosis by expressing extracellular matrices (ECM). HSCs, in the normal liver, are quiescent and activated by liver injury to become myofibroblasts that proliferate and produce ECM. It has been shown that activated HSCs (aHSCs) become a "quiescent-like" state by removal of liver insults. Therefore, deactivation agents can be a therapeutic drug for advanced liver fibrosis. Using aHSCs prepared from human induced pluripotent stem cells, we found that aHSCs were reverted to a quiescent-like state by a combination of chemical compounds that either inhibit or activate a signaling pathway, Lanifibranor, SB431542, Dorsomorphin, retinoic acid, palmitic acid and Y27632, in vitro. Based on these results, we established a high throughput system to screen agents that induce deactivation and demonstrate that a single chemical compound can induce deactivation.
Protein restriction during pregnancy alters Cdkn1c silencing, dopamine circuitry and offspring behaviour without changing expression of key neuronal marker genes
Authors: Prodani Chiara , Irvine Elaine E. , Sardini Alessandro , Gleneadie Hannah J. , Dimond Andrew , Van de Pette Mathew , John Rosalind , Kokkinou Michelle , Howes Oliver , Withers Dominic J. , Ungless Mark A. , Merkenschlager Matthias , Fisher Amanda G.
Published: April 2024

We tracked the consequences of in utero protein restriction in mice throughout their development and life course using a luciferase-based allelic reporter of imprinted Cdkn1c. Exposure to gestational low-protein diet (LPD) results in the inappropriate expression of paternally inherited Cdkn1c in the brains of embryonic and juvenile mice. These animals were characterised by a developmental delay in motor skills, and by behavioural alterations indicative of reduced anxiety. Exposure to LPD in utero resulted in significantly more tyrosine hydroxylase positive (dopaminergic) neurons in the midbrain of adult offspring as compared to age-matched, control-diet equivalents. Positron emission tomography (PET) imaging revealed an increase in striatal dopamine synthesis capacity in LPD-exposed offspring, where elevated levels of dopamine correlated with an enhanced sensitivity to cocaine. These data highlight a profound sensitivity of the developing epigenome to gestational protein restriction. Our data also suggest that loss of Cdkn1c imprinting and p57KIP2 upregulation alters the cellular composition of the developing midbrain, compromises dopamine circuitry, and thereby provokes behavioural abnormalities in early postnatal life. Molecular analyses showed that despite this phenotype, exposure to LPD solely during pregnancy did not significantly change the expression of key neuronal- or dopamine-associated marker genes in adult offspring.
Long-term outcome of adjuvant radiotherapy upon postoperative relapse of centrally located hepatocellular carcinoma: a real-world study
Authors: Tao Changcheng , Hu Nan , Liu Yue , Wang Hongwei , Wang Zhihao , Zhang Kai , Wang Liming , Chen Bo , Wu Fan , Rong Weiqi , Wu Jianxiong
Published: April 2024

Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.