bluuebunny/crossref_metadata_2025 huggingface dataset:
Superwavelength self-healing of spoof surface sonic Airy-Talbot waves
Authors: Li Hao-xiang , Liu Jing-jing , Chen Zhao-xian , Wu Kai , Liang Bin , Yang Jing , Cheng Jian-chun , Christensen Johan
Published: November 2023

Self-imaging phenomena for nonperiodic waves along a parabolic trajectory encompass both the Talbot effect and the accelerating Airy beams. Beyond the ability to guide waves along a bent trajectory, the self-imaging component offers invaluable advantages to lensless imaging comprising periodic repetition of planar field distributions. In order to circumvent thermoviscous and diffraction effects, we structure subwavelength resonators in an acoustically impenetrable surface supporting spoof surface acoustic waves (SSAWs) to provide highly confined Airy-Talbot effect, extending Talbot distances along the propagation path and compressing subwavelength lobes in the perpendicular direction. From a linear array of loudspeakers, we judiciously control the amplitude and phase of the SSAWs above the structured surface and quantitatively evaluate the self-healing performance of the Airy-Talbot effect by demonstrating how the distinctive scattering patterns remain largely unaffected against superwavelength obstacles. Furthermore, we introduce a new mechanism utilizing subwavelength Airy beam as a coding/decoding degree of freedom for acoustic communication with high information density comprising robust transport of encoded signals.
Diversification of flowering plants in space and time
Authors: Dimitrov Dimitar , Xu Xiaoting , Su Xiangyan , Shrestha Nawal , Liu Yunpeng , Kennedy Jonathan D. , Lyu Lisha , Nogués-Bravo David , Rosindell James , Yang Yong , Fjeldså Jon , Liu Jianquan , Schmid Bernhard , Fang Jingyun , Rahbek Carsten , Wang Zhiheng
Published: November 2023

The rapid diversification and high species richness of flowering plants is regarded as ‘Darwin’s second abominable mystery’. Today the global spatiotemporal pattern of plant diversification remains elusive. Using a newly generated genus-level phylogeny and global distribution data for 14,244 flowering plant genera, we describe the diversification dynamics of angiosperms through space and time. Our analyses show that diversification rates increased throughout the early Cretaceous and then slightly decreased or remained mostly stable until the end of the Cretaceous–Paleogene mass extinction event 66 million years ago. After that, diversification rates increased again towards the present. Younger genera with high diversification rates dominate temperate and dryland regions, whereas old genera with low diversification dominate the tropics. This leads to a negative correlation between spatial patterns of diversification and genus diversity. Our findings suggest that global changes since the Cenozoic shaped the patterns of flowering plant diversity and support an emerging consensus that diversification rates are higher outside the tropics.
Four-dimensional hydrogel dressing adaptable to the urethral microenvironment for scarless urethral reconstruction
Authors: Hua Yujie , Wang Kai , Huo Yingying , Zhuang Yaping , Wang Yuhui , Fang Wenzhuo , Sun Yuyan , Zhou Guangdong , Fu Qiang , Cui Wenguo , Zhang Kaile
Published: November 2023

The harsh urethral microenvironment (UME) after trauma severely hinders the current hydrogel-based urethral repair. In fact, four-dimensional (4D) consideration to mimic time-dependent physiological processes is essential for scarless urethral reconstruction, which requires balancing extracellular matrix (ECM) deposition and remodeling at different healing stages. In this study, we develop a UME-adaptable 4D hydrogel dressing to sequentially provide an early-vascularized microenvironment and later-antifibrogenic microenvironment for scarless urethral reconstruction. With the combination of dynamic boronic ester crosslinking and covalent photopolymerization, the resultant gelatin methacryloyl phenylboronic acid/cis-diol-crosslinked (GMPD) hydrogels exhibit mussel-mimetic viscoelasticity, satisfactory adhesion, and acid-reinforced stability, which can adapt to harsh UME. In addition, a temporally on-demand regulatory (TOR) technical platform is introduced into GMPD hydrogels to create a time-dependent 4D microenvironment. As a result, physiological urethral recovery is successfully mimicked by means of an early-vascularized microenvironment to promote wound healing by activating the vascular endothelial growth factor (VEGF) signaling pathway, as well as a later-antifibrogenic microenvironment to prevent hypertrophic scar formation by timing transforming growth factor-β (TGFβ) signaling pathway inhibition. Both in vitro molecular mechanisms of the physiological healing process and in vivo scarless urethral reconstruction in a rabbit model are effectively verified, providing a promising alternative for urethral injury treatment.
Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus
Authors: Whitehead Jack D. , Decool Hortense , Leyrat Cédric , Carrique Loic , Fix Jenna , Eléouët Jean-François , Galloux Marie , Renner Max
Published: November 2023

Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within nucleoproteins (N). An essential interaction between N and a C-terminal region of P tethers the L/P polymerase to the template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how the polymerase component P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to activity assays and imaging of inclusion bodies in cells. We report a 2.9 Å resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template.
Taxonomic and environmental distribution of bacterial amino acid auxotrophies
Authors: Ramoneda Josep , Jensen Thomas B. N. , Price Morgan N. , Casamayor Emilio O. , Fierer Noah
Published: November 2023

Many microorganisms are auxotrophic—unable to synthesize the compounds they require for growth. With this work, we quantify the prevalence of amino acid auxotrophies across a broad diversity of bacteria and habitats. We predicted the amino acid biosynthetic capabilities of 26,277 unique bacterial genomes spanning 12 phyla using a metabolic pathway model validated with empirical data. Amino acid auxotrophy is widespread across bacterial phyla, but we conservatively estimate that the majority of taxa (78.4%) are able to synthesize all amino acids. Our estimates indicate that amino acid auxotrophies are more prevalent among obligate intracellular parasites and in free-living taxa with genomic attributes characteristic of ‘streamlined’ life history strategies. We predicted the amino acid biosynthetic capabilities of bacterial communities found in 12 unique habitats to investigate environmental associations with auxotrophy, using data compiled from 3813 samples spanning major aquatic, terrestrial, and engineered environments. Auxotrophic taxa were more abundant in host-associated environments (including the human oral cavity and gut) and in fermented food products, with auxotrophic taxa being relatively rare in soil and aquatic systems. Overall, this work contributes to a more complete understanding of amino acid auxotrophy across the bacterial tree of life and the ecological contexts in which auxotrophy can be a successful strategy.
Design principles for sodium superionic conductors
Authors: Wang Shuo , Fu Jiamin , Liu Yunsheng , Saravanan Ramanuja Srinivasan , Luo Jing , Deng Sixu , Sham Tsun-Kong , Sun Xueliang , Mo Yifei
Published: November 2023

Motivated by the high-performance solid-state lithium batteries enabled by lithium superionic conductors, sodium superionic conductor materials have great potential to empower sodium batteries with high energy, low cost, and sustainability. A critical challenge lies in designing and discovering sodium superionic conductors with high ionic conductivities to enable the development of solid-state sodium batteries. Here, by studying the structures and diffusion mechanisms of Li-ion versus Na-ion conducting solids, we reveal the structural feature of face-sharing high-coordination sites for fast sodium-ion conductors. By applying this feature as a design principle, we discover a number of Na-ion conductors in oxides, sulfides, and halides. Notably, we discover a chloride-based family of Na-ion conductors NaxMyCl6 (M = La–Sm) with UCl3-type structure and experimentally validate with the highest reported ionic conductivity. Our findings not only pave the way for the future development of sodium-ion conductors for sodium batteries, but also consolidate design principles of fast ion-conducting materials for a variety of energy applications.
Risk to rely on soil carbon sequestration to offset global ruminant emissions
Authors: Wang Yue , de Boer Imke J. M. , Persson U. Martin , Ripoll-Bosch Raimon , Cederberg Christel , Gerber Pierre J. , Smith Pete , van Middelaar Corina E.
Published: November 2023

Carbon sequestration in grasslands has been proposed as an important means to offset greenhouse gas emissions from ruminant systems. To understand the potential and limitations of this strategy, we need to acknowledge that soil carbon sequestration is a time-limited benefit, and there are intrinsic differences between short- and long-lived greenhouse gases. Here, our analysis shows that one tonne of carbon sequestrated can offset radiative forcing of a continuous emission of 0.99 kg methane or 0.1 kg nitrous oxide per year over 100 years. About 135 gigatonnes of carbon is required to offset the continuous methane and nitrous oxide emissions from ruminant sector worldwide, nearly twice the current global carbon stock in managed grasslands. For various regions, grassland carbon stocks would need to increase by approximately 25% − 2,000%, indicating that solely relying on carbon sequestration in grasslands to offset warming effect of emissions from current ruminant systems is not feasible.
Mid-old cells are a potential target for anti-aging interventions in the elderly
Authors: Kim Young Hwa , Lee Young-Kyoung , Park Soon Sang , Park So Hyun , Eom So Yeong , Lee Young-Sam , Lee Wonhee John , Jang Juhee , Seo Daeha , Kang Hee Young , Kim Jin Cheol , Lim Su Bin , Yoon Gyesoon , Kim Hong Seok , Kim Jang-Hee , Park Tae Jun
Published: November 2023

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.
Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
Authors: Liau Wei-Siang , Zhao Qiongyi , Bademosi Adekunle , Gormal Rachel S. , Gong Hao , Marshall Paul R. , Periyakaruppiah Ambika , Madugalle Sachithrani U. , Zajaczkowski Esmi L. , Leighton Laura J. , Ren Haobin , Musgrove Mason , Davies Joshua , Rauch Simone , He Chuan , Dickinson Bryan C. , Li Xiang , Wei Wei , Meunier Frédéric A. , Fernández-Moya Sandra M. , Kiebler Michael A. , Srinivasan Balakumar , Banerjee Sourav , Clark Michael , Spitale Robert C. , Bredy Timothy W.
Published: November 2023

Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules that are involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are localized to the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated. Using lncRNA capture-seq, we identified a specific set of lncRNAs that accumulate in the synaptic compartment within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Among these was a splice variant related to the stress-associated lncRNA, Gas5. RNA immunoprecipitation followed by mass spectrometry and single-molecule imaging revealed that this Gas5 isoform, in association with the RNA binding proteins G3BP2 and CAPRIN1, regulates the activity-dependent trafficking and clustering of RNA granules. In addition, we found that cell-type-specific, activity-dependent, and synapse-specific knockdown of the Gas5 variant led to impaired fear extinction memory. These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and RNA condensates in the synaptic compartment.
Orthosteric and allosteric modulation of human HCAR2 signaling complex
Authors: Mao Chunyou , Gao Mengru , Zang Shao-Kun , Zhu Yanqing , Shen Dan-Dan , Chen Li-Nan , Yang Liu , Wang Zhiwei , Zhang Huibing , Wang Wei-Wei , Shen Qingya , Lu Yanhui , Ma Xin , Zhang Yan
Published: November 2023

Hydroxycarboxylic acids are crucial metabolic intermediates involved in various physiological and pathological processes, some of which are recognized by specific hydroxycarboxylic acid receptors (HCARs). HCAR2 is one such receptor, activated by endogenous β-hydroxybutyrate (3-HB) and butyrate, and is the target for Niacin. Interest in HCAR2 has been driven by its potential as a therapeutic target in cardiovascular and neuroinflammatory diseases. However, the limited understanding of how ligands bind to this receptor has hindered the development of alternative drugs able to avoid the common flushing side-effects associated with Niacin therapy. Here, we present three high-resolution structures of HCAR2-Gi1 complexes bound to four different ligands, one potent synthetic agonist (MK-6892) bound alone, and the two structures bound to the allosteric agonist compound 9n in conjunction with either the endogenous ligand 3-HB or niacin. These structures coupled with our functional and computational analyses further our understanding of ligand recognition, allosteric modulation, and activation of HCAR2 and pave the way for the development of high-efficiency drugs with reduced side-effects.
HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes
Authors: Li Wenwei , Qin Zhuan , Nand Elizabeth , Grunst Michael W. , Grover Jonathan R. , Bess Julian W. , Lifson Jeffrey D. , Zwick Michael B. , Tagare Hemant D. , Uchil Pradeep D. , Mothes Walther
Published: November 2023

Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD41–4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes5–13. Here we used cryo-electron tomography to monitor Env–CD4 interactions at the membrane–membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env–CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env–CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design.
Venom-gland transcriptomics and venom proteomics of the Tibellus oblongus spider
Authors: Korolkova Yuliya , Mikov Alexander , Lobas Anna , Solovyeva Elizaveta , Surin Alexey , Andreev Yaroslav , Gorshkov Mikhail , Kozlov Sergey
Published: November 2023

The Tibellus oblongus spider is an active hunter that does not spin webs and remains highly underinvestigated in terms of the venom composition. Here, we describe venom glands transcriptome and venom proteome analysis for unveiling the polypeptide composition of Tibellus oblongus spider venom. The resulting EST database includes 1733 records, including 1263 nucleotide sequences with ORFs, of these 942 have been identified as toxin-coding. The database of peptide sequences was built based on of the transcriptomics results. It contains 217 new toxins, 212 of them were detected in the T. oblongus venom by the proteomics.
Investigation of erosion-corrosion failure of API X52 carbon steel pipeline
Authors: Abdu Mahmoud T. , Khalifa Waleed , Abdelrahman Maiada S.
Published: November 2023

A failure analysis of API X52 steel pipeline was conducted. The investigation included complete material characterizations using tensile and hardness testing, optical microscope, SEM, and EDS. The main failure occurred in the downstream pipe located near the welded joint at the elbow outlet instead of elbow which was interesting. The main mechanism of failure was found to be erosion-corrosion mechanism that caused breakdown of the protective FeCO3 film, thinning of the downstream pipe, and finally failure. It is believed that the erosion-corrosion was induced by sand impingement due to turbulent flow that was promoted by sudden change in the flow cross section between the elbow inlet and upstream pipe and poor welding quality of joint at the elbow outlet.
A novel chaotic and neighborhood search-based artificial bee colony algorithm for solving optimization problems
Authors: Xiao Wen-sheng , Li Guang-xin , Liu Chao , Tan Li-ping
Published: November 2023

With the development of artificial intelligence, numerous researchers are attracted to study new heuristic algorithms and improve traditional algorithms. Artificial bee colony (ABC) algorithm is a swarm intelligence optimization algorithm inspired by the foraging behavior of honeybees, which is one of the most widely applied methods to solve optimization problems. However, the traditional ABC has some shortcomings such as under-exploitation and slow convergence, etc. In this study, a novel variant of ABC named chaotic and neighborhood search-based ABC algorithm (CNSABC) is proposed. The CNSABC contains three improved mechanisms, including Bernoulli chaotic mapping with mutual exclusion mechanism, neighborhood search mechanism with compression factor, and sustained bees. In detail, Bernoulli chaotic mapping with mutual exclusion mechanism is introduced to enhance the diversity and the exploration ability. To enhance the convergence efficiency and exploitation capability of the algorithm, the neighborhood search mechanism with compression factor and sustained bees are presented. Subsequently, a series of experiments are conducted to verify the effectiveness of the three presented mechanisms and the superiority of the proposed CNSABC, the results demonstrate that the proposed CNSABC has better convergence efficiency and search ability. Finally, the CNSABC is applied to solve two engineering optimization problems, experimental results show that CNSABC can produce satisfactory solutions.
Unraveling the molecular links between benzopyrene exposure, NASH, and HCC: an integrated bioinformatics and experimental study
Authors: Yang Zheming , Li Jiayin , Song Haixu , Mei Zhu , Jia Xiaodong , Tian Xiaoxiang , Yan Chenghui , Han Yaling
Published: November 2023

Benzopyrene (B[a]P) is a well-known carcinogen that can induce chronic inflammation and fibrosis in the liver, leading to liver disease upon chronic exposure. Nonalcoholic steatohepatitis (NASH) is a chronic liver condition characterized by fat accumulation, inflammation, and fibrosis, often resulting in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the intricate connections between B[a]P exposure, NASH, and HCC. Through comprehensive bioinformatics analysis of publicly available gene expression profiles, we identified differentially expressed genes (DEGs) associated with B[a]P exposure, NASH, and liver cancer. Furthermore, network analysis revealed hub genes and protein–protein interactions, highlighting cellular metabolic dysfunction and disruption of DNA damage repair in the B[a]P-NASH-HCC process. Notably, HSPA1A and PPARGC1A emerged as significant genes in this pathway. To validate their involvement, we conducted qPCR analysis on cell lines and NASH mouse liver tissues and performed immunohistochemistry labeling in mouse and human HCC liver sections. These findings provide crucial insights into the potential regulatory mechanisms underlying benzopyrene-induced hepatotoxicity, shedding light on the pathogenesis of B[a]P-associated NASH and HCC. Moreover, our study suggests that HSPA1A and PPARGC1A could serve as promising therapeutic targets. Enhancing our understanding of their regulatory roles may facilitate the development of targeted therapies, leading to improved patient outcomes.
Bioinformatics analysis and machine learning approach applied to the identification of novel key genes involved in non-alcoholic fatty liver disease
Authors: Nazari Elham , Khalili-Tanha Ghazaleh , Asadnia Alireza , Pourali Ghazaleh , Maftooh Mina , Khazaei Majid , Nasiri Mohammadreza , Hassanian Seyed Mahdi , Ghayour-Mobarhan Majid , Ferns Gordon A. , Kiani Mohammad Ali , Avan Amir
Published: November 2023

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver.
Lemon extract supported green synthesis of bimetallic CuO/Ag nanoporous materials for sensitive detection of vitamin D3
Authors: Naikoo Gowhar A. , Almashali Fay M. , Habis Fatima A. S. , Bano Mustri , Rather Jahangir Ahmad , Hassan Israr U. , Sheikh Rayees Ahmad , Kannan Palanisamy , Alfagih Iman M. , Tambuwala Murtaza M.
Published: November 2023

In modern era, deficiency of Vitamin D3 is predominantly due to limited exposure to sunlight and UV radiation resulting from indoor lifestyles. Several studies have revealed that vitamin D deficiency can lead to chronic vascular inflammation, diabetes mellitus, hypertension, congestive left ventricular hypertrophy, and heart failure. This study introduces a green synthesis of novel bimetallic nanoporous composite, CuO/Ag using lemon extract. The synthesized nanoporous material, CuO/Ag@lemon extract was characterized using several analytical techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The CuO/Ag@lemon extract nanoparticles were immobilized on glassy carbon electrode (GCE) to prepare modified CuO/Ag@lemon extract–GCE interface. The electrocatalytic and electrochemical properties investigation was carried out on the modified electrode. using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and amperometry for detecting of Vitamin D3. The DPV method displayed a linear response range of 0.02–22.5 µM with a detection limit of 2.62 nM, while the amperometric method showed a broader linear range of 0.25–23.25 µM with a detection limit of 2.70 nM with 82% modified electrode stability. The designed electrode exhibited a positive response to the inclusion of Vitamin D3 with electro-oxidation, reaching steady-state within 3.4 s, with 87% reproducibility within a day. The proposed method offers a rapid and sensitive platform for detection of Vitamin D3 with minimal interference from other molecules. The early diagnosis of Vitamin D3 deficiency using modified electrodes allows for early treatment, thereby preventing severe health complications.
ALS/FTD-associated mutation in cyclin F inhibits ER-Golgi trafficking, inducing ER stress, ERAD and Golgi fragmentation
Authors: Ragagnin Audrey M. G. , Sundaramoorthy Vinod , Farzana Fabiha , Gautam Shashi , Saravanabavan Sayanthooran , Takalloo Zeinab , Mehta Prachi , Do-Ha Dzung , Parakh Sonam , Shadfar Sina , Hunter Julie , Vidal Marta , Jagaraj Cyril J. , Brocardo Mariana , Konopka Anna , Yang Shu , Rayner Stephanie L. , Williams Kelly L. , Blair Ian P. , Chung Roger S. , Lee Albert , Ooi Lezanne , Atkin Julie D.
Published: November 2023

Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative condition that is part of the same disease spectrum as frontotemporal dementia (FTD). Mutations in the CCNF gene, encoding cyclin F, are present in both sporadic and familial ALS and FTD. However, the pathophysiological mechanisms underlying neurodegeneration remain unclear. Proper functioning of the endoplasmic reticulum (ER) and Golgi apparatus compartments is essential for normal physiological activities and to maintain cellular viability. Here, we demonstrate that ALS/FTD-associated variant cyclin FS621G inhibits secretory protein transport from the ER to Golgi apparatus, by a mechanism involving dysregulation of COPII vesicles at ER exit sites. Consistent with this finding, cyclin FS621G also induces fragmentation of the Golgi apparatus and activates ER stress, ER-associated degradation, and apoptosis. Induction of Golgi fragmentation and ER stress were confirmed with a second ALS/FTD variant cyclin FS195R, and in cortical primary neurons. Hence, this study provides novel insights into pathogenic mechanisms associated with ALS/FTD-variant cyclin F, involving perturbations to both secretory protein trafficking and ER-Golgi homeostasis.
Optimal design and nonlinear dynamic characteristics of titanium /steel drill pipe composite drill string for ultra-deep drilling
Authors: Liu Qiang , Zhou Bo , Chen Feng , Li Ning , Xie Junfeng , Zhao Mifeng , Di Qinfeng , Feng Chun , Song Shengyin , Yin Chengxian
Published: November 2023

Titanium drill pipe have promising application prospects in ultra-deep drilling, but the nonlinear dynamic characteristics of composite drill strings are very complex. It is very important to use titanium drill pipe safely, economically, and effectively in the drilling process. In this paper, different schemes of the titanium/steel drill pipe composite drill string was designed, and the statics and dynamics characteristics of these composite drill strings were analyzed. The design scheme of titanium/steel composite drill strings were optimized by using whirling characteristics, dynamic stress and vibration acceleration. The results show that the titanium drill pipe can effectively improve the tensile allowance of the wellhead and reduce the whirling velocity, dynamic stress and vibration acceleration of the drill string. By comparing and analyzing the dynamic characteristics of 3 kinds of composite drill strings, the use of titanium drill pipe for the lower 2000 m of the 4′′ drill pipe have the smaller dynamic stress and lateral vibration, and less collision with the wellbore. Based on the analysis of vibration and dynamic characteristics, an optimal scheme of drilling operation parameters for the titanium/steel composite drill string was formed finally, which can provide guidance for the use of the drill string composed of titanium/steel drill pipe in natural gas drilling of ultra-deep well.
Changes in discourse on unmet need for family planning among married women in India: evidence from NFHS-5 (2019–2021)
Authors: Singh S. K. , Kashyap G. C. , Sharma Himani , Mondal Sudipta , Legare C. H.
Published: November 2023

Unmet needs for contraception in India have declined over time but the rate has not been uniform among women across geographies and socio-economic strata. Identifying the characteristics of women in communities where unmet need is still high is important to devise appropriate strategies to ensure access and uptake of modern contraceptive methods. The current study examined whether there was a national decline in unmet need over time and if regional disparities exist in unmet need. Demographic variations in unmet need based on factors such as maternal age, education, religion, caste, wealth index quintile, family size, and access to antenatal care (ANC) were also documented. Our approach was to document the prevalence of total unmet need for family planning and unmet need for spacing among married Indian women and quantify variability based on socio-economic and demographic drivers within a hierarchal framework, thus providing both macro and micro perspectives. We used data from the fourth and fifth rounds of the National Family Health Survey (NFHS) collected from all the States and Union Territories (UTs) in India. Quantile regression analysis and multilevel regression techniques were used to understand the predictors for the total unmet need for family planning and the unmet need for spacing. Results show a considerable decline in the prevalence of unmet need for family planning in India from NFHS-4 to 5 (from 12.9 to 9.3%) in the last six6 years. The north-eastern states show a significant reduction in unmet need for family planning in Manipur (17.8%), Nagaland (13.5%), and followed by Sikkim (9.1%). The predictors such as years of schooling, place of residence, caste, religion, wealth quintile, number of antenatal care (ANC) visits, and children ever born have a significant association with unmet needs for family planning and spacing among married women in India. There is a significant association between years of schooling with the total unmet needs for family planning at (q25) quantiles and the unmet need for spacing at (q25, q50) quantiles. Results reveal that the demand for unmet need for spacing and limiting was the highest among the women in the age categories 15–19 (17.8%) and 20–24 (17.3%). The demand for limiting was the highest (6.8%) among Muslim women. Across wealth quantile categories, the overall unmet demand (11.4%) for spacing and limiting was the highest among the women in the lowest socioeconomic groups. We conclude that greater access to frontline health workers among young wives, and significant investment in education in general, will continue to reduce the unmet needs for family planning in India.
Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats
Authors: Nagae Mayuko , Yamada Koki , Enomoto Yuki , Kometani Mari , Tsuchida Hitomi , Panthee Arvinda , Nonogaki Miku , Matsunaga Nao , Takizawa Marina , Matsuzaki Sena , Hirabayashi Masumi , Inoue Naoko , Tsukamura Hiroko , Uenoyama Yoshihisa
Published: November 2023

The gonadotropin-releasing hormone (GnRH) pulse and surge are considered to be generated by arcuate kisspeptin/neurokinin B/dynorphin A (KNDy) neurons and anteroventral periventricular nucleus (AVPV) kisspeptin neurons, respectively, in female rodents. The majority of KNDy and AVPV kisspeptin neurons express κ-opioid receptors (KORs, encoded by Oprk1) in female rodents. Thus, this study aimed to investigate the effect of a conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons on the luteinizing hormone (LH) pulse/surge and fertility using Kiss1-floxed/Oprk1-Cre rats, in which Kiss1 was deleted in cells expressing or once expressed the Oprk1/Cre. The Kiss1-floxed/Oprk1-Cre female rats, with Kiss1 deleted in a majority of KNDy neurons, showed normal puberty while having a one-day longer estrous cycle and fewer pups than Kiss1-floxed controls. Notably, ovariectomized (OVX) Kiss1-floxed/Oprk1-Cre rats showed profound disruption of LH pulses in the presence of a diestrous level of estrogen but showed apparent LH pulses without estrogen treatment. Furthermore, Kiss1-floxed/Oprk1-Cre rats, with Kiss1 deleted in approximately half of AVPV kisspeptin neurons, showed a lower peak of the estrogen-induced LH surge than controls. These results suggest that arcuate and AVPV kisspeptin neurons expressing or having expressed Oprk1 have a role in maintaining normal GnRH pulse and surge generation, the normal length of the estrous cycle, and the normal offspring number in female rats.
Markers of insulin resistance associated with non-alcoholic fatty liver disease in non-diabetic population
Authors: Zeng Pei , Cai Xiangsheng , Yu Xiaozhou , Gong Linjing
Published: November 2023

Insulin resistance (IR) plays an important role in the development of non-alcoholic fatty liver disease (NAFLD). IR markers are divided into two types: (1) insulin-based IR marker, homeostatic model assessment of IR (HOMA-IR); and (2) non-insulin-based IR markers, such as triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), and metabolic score for IR (METS-IR). The non-insulin-based IR markers are often associated with lipids. The aim of this study was to analyse the association between IR markers and NAFLD in non-diabetic population. Baseline data of NAFLD and non-NAFLD groups were compared. Logistic regression was used to evaluate the relationship between five IR markers and NAFLD risk. The odds ratios (ORs) and 95% confidence intervals (CIs) of IR markers were calculated. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the ability of different IR markers to detect NAFLD. Subgroup analyses were performed in obese and non-obese subgroups. This study found a positive correlation between NAFLD risk and elevation in five IR markers (HOMA-IR, TyG, TyG-BMI, TG/HDL-c, and METS-IR). In non-obese subjects, the AUC of TyG-BMI was larger than that of the other four IR markers to detect NAFLD. The AUC of HOMA-IR was larger than that of the other four IR markers to detect NAFLD in obese subjects. In non-diabetic population, the five IR markers are associated with the risk of NAFLD, including non-obese and obese NAFLD. TyG-BMI and HOMA-IR can be used to detect non-obese and obese NAFLD, respectively, with better detection ability compared with the other IR markers.
Lipidure-based micropattern fabrication for stereotyping cell geometry
Authors: Grespin Drew B. , Niven Talen G. , Babson Riley O. , Kushner Erich J.
Published: November 2023

Cell autonomous behaviors such as migration and orchestration of cell polarity programs are required for physiological tissue formation. Micropatterns are cell-adhesive shapes that confine cell(s) to a user defined geometry. This biophysical confinement allows researchers to standardize the cell shape, and in doing so, stereotype organelle and cytoskeletal systems that can have an arbitrary organization. Thus, micropatterning can be a powerful tool in interrogation of polarity programs by enforcing a homogenous cell shape and cytoskeletal organization. A major drawback of this approach is the equipment and reagent costs associated with fabrication. Here, we provide a characterization of a compound called Lipidure (2-Methacryloyloxy ethyl phosphorylcholine) that is up to 40X less expensive than other cell repulsive coating agents. We found that Lipidure is an effective cell-repulsive agent for photolithography-based micropattern fabrication. Our results demonstrate that Lipidure is sensitive to deep UV irradiation for photolithography masking, stable in both benchtop and aqueous environments, non-toxic in prolonged culture, and effective at constraining cell geometry for quantification of cytoskeletal systems.
Monte Carlo based dosimetry of extraoral photobiomodulation for prevention of oral mucositis
Authors: Yaroslavsky Anna N. , Iorizzo Tyler W. , Juliano Amy F. , Adnan Ather , Carroll James D. , Sonis Stephen T. , Duncan Christine N. , London Wendy B. , Treister Nathaniel S.
Published: November 2023

Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention. The goal of this study was to develop a clinically viable protocol for extraoral PBMT. Monte Carlo modeling was used to predict the distribution of 850 nm light for four treatment sites, using anatomical data obtained from MRI and optical properties from the literature. Simulated incident light power density was limited to 399 mW/cm2 to ensure treatment safety and to prevent tissue temperature increase. The results reveal that total tissue thickness determines fluence rate at the oral mucosa, whereas the thickness of individual tissue layers and melanin content are of minor importance. Due to anatomical differences, the fluence rate varied greatly among patients. Despite these variations, a universal protocol was established using a median treatment time methodology. The determined median treatment times required to deliver efficacious dose between 1 and 6 J/cm2 were within 15 min. The developed PBMT protocol can be further refined using the combination of pretreatment imaging and the Monte Carlo simulation approach implemented in this study.
Interplay between stress, sleep, and BDNF in a high-risk sample of young adults
Authors: Varghese Nimmy , Buergin David , Boonmann Cyril , Stadler Christina , Schmid Marc , Eckert Anne , Unternaehrer Eva
Published: November 2023

Children in institutional care have a high risk to experience childhood adversities (CAs), with consequences for physical and mental well-being. The long-term effects of CAs on the brain, including consequences for neuronal plasticity and sleep, are poorly understood. This study examined the interplay between stress (including CAs), sleep, and brain-derived neurotrophic factor (BDNF), a prominent marker for neuronal plasticity. Participants (N = 131, mean age = 26.3±3.4 years, 40 females) with residential youth-care history completed questionnaires measuring CAs (Childhood Trauma Questionnaire, CTQ), psychological well-being (World Health Organization-Five Well-Being Index, WHO-5), and sleep disturbances (Pittsburgh Sleep Quality Inventory, PSQI). Hair cortisol and serum BDNF concentration were measured using enzyme-linked immunosorbent assays. The analyses were conducted by using bootstrap regression models. There was no association of stress parameters or sleep with BDNF concentration. However, we found a significant association of CAs and well-being with sleep disturbances. Last, we found an association between CAs and BDNF in sleep-healthy but not sleep-disturbed participants. Our findings indicated a role of sleep disturbance in the association between stress and BDNF. Still, further studies are warranted using vulnerable groups at-risk to understand long-term effects on mental health and sleep.
Globally shared TCR repertoires within the tumor-infiltrating lymphocytes of patients with metastatic gynecologic cancer
Authors: Kim Taehoon , Lim Hyeonseob , Jun Soyeong , Park Junsik , Lee Dongin , Lee Ji Hyun , Lee Jung-Yun , Bang Duhee
Published: November 2023

Gynecologic cancer, including ovarian cancer and endometrial cancer, is characterized by morphological and molecular heterogeneity. Germline and somatic testing are available for patients to screen for pathogenic variants in genes such as BRCA1/2. Tissue expression levels of immunogenomic markers such as PD-L1 are also being used in clinical research. The basic therapeutic approach to gynecologic cancer combines surgery with chemotherapy. Immunotherapy, while not yet a mainstream treatment for gynecologic cancers, is advancing, with Dostarlimab recently receiving approval as a treatment for endometrial cancer. The goal remains to harness stimulated immune cells in the bloodstream to eradicate multiple metastases, a feat currently deemed challenging in a typical clinical setting. For the discovery of novel immunotherapy-based tumor targets, tumor-infiltrating lymphocytes (TILs) give a key insight on tumor-related immune activities by providing T cell receptor (TCR) sequences. Understanding the TCR repertoires of TILs in metastatic tissues and the circulation is important from an immunotherapy standpoint, as a subset of T cells in the blood have the potential to help kill tumor cells. To explore the relationship between distant tissue biopsy regions and blood circulation, we investigated the TCR beta chain (TCRβ) in bulk tumor and matched blood samples from 39 patients with gynecologic cancer. We found that the TCR clones of TILs at different tumor sites were globally shared within patients and had high overlap with the TCR clones in peripheral blood.
Clinical effects of different virtual reality presentation content on anxiety and pain: a randomized controlled trial
Authors: Yamashita Yoshio , Aijima Reona , Danjo Atsushi
Published: November 2023

Many patients are frightened of or anxious about dental treatment. We have recently reported our use of virtual reality (VR) to alleviate the fear and anxiety experienced during oral surgical procedures However, the effectiveness of VR in alleviating anxiety varies greatly between individuals. We therefore investigated whether the content of the VR presentation made any difference to its effect in alleviating anxiety, and whether it had any analgesic effect. The study subjects experienced one of two different types of VR presentation and were asked to complete a questionnaire about any changes in their anxiety during the procedure, including a visual analog scale (VAS) score. As an objective evaluation, changes in pain threshold during the VR presentation were investigated using PainVision. For those patients who experienced a presentation showing a natural landscape, the change in VAS score was − 13.3 ± 28.7 mm, whereas for those who experienced a presentation showing a video game the change was − 22.2 ± 32.1 mm, an even greater reduction. In a pain questionnaire completed by individuals who had experienced the video game presentations, approximately 70% reported that their pain had diminished. An objective evaluation of pain threshold also showed that the pain threshold of individuals increased by around 3% while experiencing the natural landscape VR presentation, but that while experiencing the video game presentation, it increased significantly by around 15% compared with baseline. These results show that the content of the presentation affected not only the rate of decrease in anxiety, but also the pain threshold.
A new large area MCP-PMT for high energy detection
Authors: Chen Lin , Yang Huizhen , Wang Xingchao , Tian Liping , Ding Dongyan , Wang Yunji , Ji Ke , Zheng Pengxiang , Luo Ting , She Chenye
Published: November 2023

20-inch Large area photomultiplier tube based on microchannel plate (MCP-PMT) is newly developed in China. It is widely used in high energy detection experiments such as Jiangmen Underground Neutrino Observatory (JUNO), China JinPing underground Laboratory (CJPL) and Large High Altitude Air Shower Observatory (LHAASO). To overcome the poor time performance of the existing MCP-PMT, a new design of large area MCP-PMT is proposed in this paper. Three-dimensional models are developed in CST Studio Suite to validate its feasibility. Effects of the size and bias voltage of the focusing electrodes and MCP configuration on the collection efficiency (CE) and time performance are studied in detail using the finite integral technique and Monte Carlo method. Based on the simulation results, the optimized operating and geometry parameters are chosen. Results show that the mean ratio of photoelectrons landing on the MCP active area is 97.5%. The acceptance fraction of the impinging photoelectrons is close to 100% due to the emission of multiple secondary electrons when hitting the MCP top surface. The mean transit time spread (TTS) of the photoelectrons from the photocathode is 1.48 ns.
Biostimulants and herbicides a tool to reduce non-commercial yield tubers and improve potato yield structure
Authors: Ginter Agnieszka , Zarzecka Krystyna , Gugała Marek , Mystkowska Iwona
Published: November 2023

The basis for the study was a field experiment conducted in 2012–2014 in the production fields of multi-branch Soleks company in Wojnów, the district of Siedlce in eastern Poland. The experiment was established in a split-plot arrangement as a two-factor experiment in three replications. The first factor were: three cultivars of edible potato—Bartek, Gawin, Honorata, and the second factor were: five objects of potato cultivation with herbicides and biostimulants: 1—Control object—without chemical protection, 2—herbicide Harrier 295 ZC, 3—herbicide Harrier 295 ZC + biostimulant Kelpak SL, 4—herbicide Sencor 70 WG, 5—herbicide Sencor 70 WG + biostimulant Asahi SL. The aim of the study was to reduce the non-commercial potato yield and improve the yield structure through the application of biostimulants and herbicides, and to determine the relationship between weed infestation and tuber yield. The least amount of weeds and the best destruction efficiency were obtained after the application of herbicide Sencor 70 WG + biostimulant Asahi SL and herbicide Harrier 295 ZC + biostimulant Kelpak SL. Effective reduction of weed infestation contributed to improvement of yield structure and reduction of potato non-commercial yield. Based on correlation coefficients, a significant relationship between weed infestation and potato non-commercial yield was shown.