bluuebunny/crossref_metadata_2025 huggingface dataset:
Noncovalent synthesis of homo and hetero-architectures of supramolecular polymers via secondary nucleation
Authors: Kotha Srinu , Sahu Rahul , Yadav Aditya Chandrakant , Sharma Preeti , Kumar B. V. V. S. Pavan , Reddy Sandeep K. , Rao Kotagiri Venkata
Published: May 2024

The synthesis of supramolecular polymers with controlled architecture is a grand challenge in supramolecular chemistry. Although living supramolecular polymerization via primary nucleation has been extensively studied for controlling the supramolecular polymerization of small molecules, the resulting supramolecular polymers have typically exhibited one-dimensional morphology. In this report, we present the synthesis of intriguing supramolecular polymer architectures through a secondary nucleation event, a mechanism well-established in protein aggregation and the crystallization of small molecules. To achieve this, we choose perylene diimide with 2-ethylhexyl chains at the imide position as they are capable of forming dormant monomers in solution. Activating these dormant monomers via mechanical stimuli and hetero-seeding using propoxyethyl perylene diimide seeds, secondary nucleation event takes over, leading to the formation of three-dimensional spherical spherulites and scarf-like supramolecular polymer heterostructures, respectively. Therefore, the results presented in this study propose a simple molecular design for synthesizing well-defined supramolecular polymer architectures via secondary nucleation.
Waveguide-integrated twisted bilayer graphene photodetectors
Authors: Wu Qinci , Qian Jun , Wang Yuechen , Xing Luwen , Wei Ziyi , Gao Xin , Li Yurui , Liu Zhongfan , Liu Hongtao , Shu Haowen , Yin Jianbo , Wang Xingjun , Peng Hailin
Published: May 2024

Graphene photodetectors have exhibited high bandwidth and capability of being integrated with silicon photonics (SiPh), holding promise for future optical communication devices. However, they usually suffer from a low photoresponsivity due to weak optical absorption. In this work, we have implemented SiPh-integrated twisted bilayer graphene (tBLG) detectors and reported a responsivity of 0.65 A W–1 for telecom wavelength 1,550 nm. The high responsivity enables a 3-dB bandwidth of >65 GHz and a high data stream rate of 50 Gbit s–1. Such high responsivity is attributed to the enhanced optical absorption, which is facilitated by van Hove singularities in the band structure of high-mobility tBLG with 4.1o twist angle. The uniform performance of the fabricated photodetector arrays demonstrates a fascinating prospect of large-area tBLG as a material candidate for heterogeneous integration with SiPh.
Diastereo-divergent synthesis of chiral hindered ethers via a synergistic calcium(II)/gold(I) catalyzed cascade hydration/1,4-addition reaction
Authors: Lin Xiangfeng , Mu Xia , Cui Hongqiang , Li Qian , Feng Zhaochi , Liu Yan , Li Guohui , Li Can
Published: May 2024

Hindered ethers are ubiquitous in natural products and bioactive molecules. However, developing an efficient method for the stereocontrolled synthesis of all stereoisomers of chiral hindered ethers is highly desirable but challenging. Here we show a strategy that utilizes in situ-generated water as a nucleophile in an asymmetric cascade reaction involving two highly reactive intermediates, 3-furyl methyl cations and ortho-quinone methides (o-QMs), to synthesize chiral hindered ethers. The Ca(II)/Au(I) synergistic catalytic system enables the control of diastereoselectivity and enantioselectivity by selecting suitable chiral phosphine ligands in this cascade hydration/1,4-addition reaction, affording all four stereoisomers of a diverse range of chiral tetra-aryl substituted ethers with high diastereoselectivities (up to >20/1) and enantioselectivities (up to 95% ee). This work provides an example of chiral Ca(II)/Au(I) bimetallic catalytic system controlling two stereogenic centers via a cascade reaction in a single operation.
Isostructural doping for organic persistent mechanoluminescence
Authors: Xie Zongliang , Xue Yufeng , Zhang Xianhe , Chen Junru , Lin Zesen , Liu Bin
Published: May 2024

Mechanoluminescence, featuring light emission triggered by mechanical stimuli, holds immense promise for diverse applications. However, most organic Mechanoluminescence materials suffer from short-lived luminescence, limiting their practical applications. Herein, we report isostructural doping as a valuable strategy to address this challenge. By strategically modifying the host matrices with specific functional groups and simultaneously engineering guest molecules with structurally analogous features for isostructural doping, we have successfully achieved diverse multicolor and high-efficiency persistent mechanoluminescence materials with ultralong lifetimes. The underlying persistent mechanoluminescence mechanism and the universality of the isostructural doping strategy are also clearly elucidated and verified. Moreover, stress sensing devices are fabricated to show their promising prospects in high-resolution optical storage, pressure-sensitive displays, and stress monitoring. This work may facilitate the development of highly efficient organic persistent mechanoluminescence materials, expanding the horizons of next-generation smart luminescent technologies.
Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors
Authors: Roy Koustav , Zhou Xuzhao , Otani Rintaro , Yuan Ping-Chuan , Ioka Shuji , Vogt Kaspar E. , Kondo Tamae , Farag Nouran H. T. , Ijiri Haruto , Wu Zhaofa , Chitose Youhei , Amezawa Mao , Uygun David S. , Cherasse Yoan , Nagase Hiroshi , Li Yulong , Yanagisawa Masashi , Abe Manabu , Basheer Radhika , Wang Yi-Qun , Saitoh Tsuyoshi , Lazarus Michael
Published: May 2024

Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli. Adenosine emerges as a promising candidate molecule for activating indirect pathway neurons of the NAc expressing adenosine A2A receptors (A2ARs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A2ARs (A2AR PAM) that can be rapidly photoactivated with visible light (λ > 400 nm) and used it optoallosterically to induce SWS in the NAc of freely behaving male mice by increasing the activity of extracellular adenosine derived from astrocytic and neuronal activity.
Primary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma
Authors: Joo Victor , Abdelhamid Karim , Noto Alessandra , Latifyan Sofiya , Martina Federica , Daoudlarian Douglas , De Micheli Rita , Pruijm Menno , Peters Solange , Hullin Roger , Gaide Olivier , Pantaleo Giuseppe , Obeid Michel
Published: May 2024

The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69). In the second step, talimogene laherparepvec (T-VEC) injection further enhances effector function by switching CD4 and CD8 cells from central memory to effector memory profiles, enhancing Th1 responses, and boosting cytotoxic and proliferative activities. In addition, cytokine release (IL-6, IL-18, sCD25, CCL-2, CCL-4) is enhanced and the frequency of circulating regulatory T cells is increased. Notably, no histologic signs of allograft rejection are observed in consecutive end-myocardial biopsies. These findings provide valuable insights into the dynamics of T cell activation and differentiation and suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T cell function while maintaining allograft tolerance.
Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases
Authors: Karlsson Linda , Vogel Jacob , Arvidsson Ida , Åström Kalle , Janelidze Shorena , Blennow Kaj , Palmqvist Sebastian , Stomrud Erik , Mattsson-Carlgren Niklas , Hansson Oskar
Published: May 2024

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.
Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Authors: Zhang Chao , Rehman Michael , Tian Xin , Pei Steven Lim Cho , Gu Jianlei , Bell Thomas A. , Dong Ke , Tham Ming Shen , Cai Yiqiang , Wei Zemeng , Behrens Felix , Jetten Anton M. , Zhao Hongyu , Lek Monkol , Somlo Stefan
Published: May 2024

Mouse models of autosomal dominant polycystic kidney disease (ADPKD) show that intact primary cilia are required for cyst growth following the inactivation of polycystin-1. The signaling pathways underlying this process, termed cilia-dependent cyst activation (CDCA), remain unknown. Using translating ribosome affinity purification RNASeq on mouse kidneys with polycystin-1 and cilia inactivation before cyst formation, we identify the differential ‘CDCA pattern’ translatome specifically dysregulated in kidney tubule cells destined to form cysts. From this, Glis2 emerges as a candidate functional effector of polycystin signaling and CDCA. In vitro changes in Glis2 expression mirror the polycystin- and cilia-dependent changes observed in kidney tissue, validating Glis2 as a cell culture-based indicator of polycystin function related to cyst formation. Inactivation of Glis2 suppresses polycystic kidney disease in mouse models of ADPKD, and pharmacological targeting of Glis2 with antisense oligonucleotides slows disease progression. Glis2 transcript and protein is a functional target of CDCA and a potential therapeutic target for treating ADPKD.
An artificial visual neuron with multiplexed rate and time-to-first-spike coding
Authors: Li Fanfan , Li Dingwei , Wang Chuanqing , Liu Guolei , Wang Rui , Ren Huihui , Tang Yingjie , Wang Yan , Chen Yitong , Liang Kun , Huang Qi , Sawan Mohamad , Qiu Min , Wang Hong , Zhu Bowen
Published: May 2024

Human visual neurons rely on event-driven, energy-efficient spikes for communication, while silicon image sensors do not. The energy-budget mismatch between biological systems and machine vision technology has inspired the development of artificial visual neurons for use in spiking neural network (SNN). However, the lack of multiplexed data coding schemes reduces the ability of artificial visual neurons in SNN to emulate the visual perception ability of biological systems. Here, we present an artificial visual spiking neuron that enables rate and temporal fusion (RTF) coding of external visual information. The artificial neuron can code visual information at different spiking frequencies (rate coding) and enables precise and energy-efficient time-to-first-spike (TTFS) coding. This multiplexed sensory coding scheme could improve the computing capability and efficacy of artificial visual neurons. A hardware-based SNN with the RTF coding scheme exhibits good consistency with real-world ground truth data and achieves highly accurate steering and speed predictions for self-driving vehicles in complex conditions. The multiplexed RTF coding scheme demonstrates the feasibility of developing highly efficient spike-based neuromorphic hardware.
Optofluidic crystallithography for directed growth of single-crystalline halide perovskites
Authors: Chen Xue-Guang , Lin Linhan , Huang Guan-Yao , Chen Xiao-Mei , Li Xiao-Ze , Zhou Yun-Ke , Zou Yixuan , Fu Tairan , Li Peng , Li Zhengcao , Sun Hong-Bo
Published: May 2024

Crystallization is a fundamental phenomenon which describes how the atomic building blocks such as atoms and molecules are arranged into ordered or quasi-ordered structure and form solid-state materials. While numerous studies have focused on the nucleation behavior, the precise and spatiotemporal control of growth kinetics, which dictates the defect density, the micromorphology, as well as the properties of the grown materials, remains elusive so far. Herein, we propose an optical strategy, termed optofluidic crystallithography (OCL), to solve this fundamental problem. Taking halide perovskites as an example, we use a laser beam to manipulate the molecular motion in the native precursor environment and create inhomogeneous spatial distribution of the molecular species. Harnessing the coordinated effect of laser-controlled local supersaturation and interfacial energy, we precisely steer the ionic reaction at the growth interface and directly print arbitrary single crystals of halide perovskites of high surface quality, crystallinity, and uniformity at a high printing speed of 102 μm s−1. The OCL technique can be potentially extended to the fabrication of single-crystal structures beyond halide perovskites, once crystallization can be triggered under the laser-directed local supersaturation.
Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment
Authors: Bhattarai Kashi Raj , Mobley Robert J. , Barnett Kelly R. , Ferguson Daniel C. , Hansen Baranda S. , Diedrich Jonathan D. , Bergeron Brennan P. , Yoshimura Satoshi , Yang Wenjian , Crews Kristine R. , Manring Christopher S. , Jabbour Elias , Paietta Elisabeth , Litzow Mark R. , Kornblau Steven M. , Stock Wendy , Inaba Hiroto , Jeha Sima , Pui Ching-Hon , Cheng Cheng , Pruett-Miller Shondra M. , Relling Mary V. , Yang Jun J. , Evans William E. , Savic Daniel
Published: May 2024

Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents.
Structural mechanism of voltage-gated sodium channel slow inactivation
Authors: Chen Huiwen , Xia Zhanyi , Dong Jie , Huang Bo , Zhang Jiangtao , Zhou Feng , Yan Rui , Shi Yiqiang , Gong Jianke , Jiang Juquan , Huang Zhuo , Jiang Daohua
Published: May 2024

Voltage-gated sodium (NaV) channels mediate a plethora of electrical activities. NaV channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of NaV channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying NaV channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaVEh (NaVEhΔN) results in a slow-inactivated channel, and present cryo-EM structure of NaVEhΔN in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaVEh structure, NaVEhΔN undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into NaV channel slow inactivation.
Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy
Authors: Yan Jiaqi , Bhadane Rajendra , Ran Meixin , Ma Xiaodong , Li Yuanqiang , Zheng Dongdong , Salo-Ahen Outi M. H. , Zhang Hongbo
Published: May 2024

The metal-nucleic acid nanocomposites, first termed metal-nucleic acid frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the synthesis efficiency and stability of MNFs by increasing oligonucleotide folding and entanglement probabilities during the reaction. Besides, longer oligonucleotides provide upgraded metal ions binding conditions, facilitating MNFs to load macromolecular protein drugs at room temperature. Furthermore, longer oligonucleotides facilitate functional expansion of nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, we build an interferon regulatory factor-1(IRF-1) loaded Ca2+/(aptamer-deoxyribozyme) MNF to target regulate glucose transporter (GLUT-1) expression in human epidermal growth factor receptor-2 (HER-2) positive gastric cancer cells. This MNF nanodevice disrupts GSH/ROS homeostasis, suppresses DNA repair, and augments ROS-mediated DNA damage therapy, with tumor inhibition rate up to 90%. Our work signifies a significant advancement towards an era of universal MNF application.
Edible mycelium as proliferation and differentiation support for anchorage-dependent animal cells in cultivated meat production
Authors: Ogawa Minami , Kermani Alex S. , Huynh Mayrene J. , Baar Keith , Leach J. Kent , Block David E.
Published: May 2024

Cultivated meat production requires bioprocess optimization to achieve cell densities that are multiple orders of magnitude higher compared to conventional cell culture techniques. These processes must maximize resource efficiency and cost-effectiveness by attaining high cell growth productivity per unit of medium. Microcarriers, or carriers, are compatible with large-scale bioreactor use, and offer a large surface-area-to-volume ratio for the adhesion and proliferation of anchorage-dependent animal cells. An ongoing challenge persists in the efficient retrieval of cells from the carriers, with conflicting reports on the effectiveness of trypsinization and the need for additional optimization measures such as carrier sieving. To surmount this issue, edible carriers have been proposed, offering the advantage of integration into the final food product while providing opportunities for texture, flavor, and nutritional incorporation. Recently, a proof of concept (POC) utilizing inactivated mycelium biomass derived from edible filamentous fungus demonstrated its potential as a support structure for myoblasts. However, this POC relied on a model mammalian cell line combination with a single mycelium species, limiting realistic applicability to cultivated meat production. This study aims to advance the POC. We found that the species of fungi composing the carriers impacts C2C12 myoblast cell attachment—with carriers derived from Aspergillus oryzae promoting the best proliferation. C2C12 myoblasts effectively differentiated on mycelium carriers when induced in myogenic differentiation media. Mycelium carriers also supported proliferation and differentiation of bovine satellite cells. These findings demonstrate the potential of edible mycelium carrier technology to be readily adapted in product development within the cultivated meat industry.
Chromatin accessibility during human first-trimester neurodevelopment
Authors: Mannens Camiel C. A. , Hu Lijuan , Lönnerberg Peter , Schipper Marijn , Reagor Caleb C. , Li Xiaofei , He Xiaoling , Barker Roger A. , Sundström Erik , Posthuma Danielle , Linnarsson Sten
Published: May 2024

The human brain develops through a tightly organized cascade of patterning events, induced by transcription factor expression and changes in chromatin accessibility. Although gene expression across the developing brain has been described at single-cell resolution1, similar atlases of chromatin accessibility have been primarily focused on the forebrain2–4. Here we describe chromatin accessibility and paired gene expression across the entire developing human brain during the first trimester (6–13 weeks after conception). We defined 135 clusters and used multiomic measurements to link candidate cis-regulatory elements to gene expression. The number of accessible regions increased both with age and along neuronal differentiation. Using a convolutional neural network, we identified putative functional transcription factor-binding sites in enhancers characterizing neuronal subtypes. We applied this model to cis-regulatory elements linked to ESRRB to elucidate its activation mechanism in the Purkinje cell lineage. Finally, by linking disease-associated single nucleotide polymorphisms to cis-regulatory elements, we validated putative pathogenic mechanisms in several diseases and identified midbrain-derived GABAergic neurons as being the most vulnerable to major depressive disorder-related mutations. Our findings provide a more detailed view of key gene regulatory mechanisms underlying the emergence of brain cell types during the first trimester and a comprehensive reference for future studies related to human neurodevelopment.
Sleep pressure modulates single-neuron synapse number in zebrafish
Authors: Suppermpool Anya , Lyons Declan G. , Broom Elizabeth , Rihel Jason
Published: May 2024

Sleep is a nearly universal behaviour with unclear functions1. The synaptic homeostasis hypothesis proposes that sleep is required to renormalize the increases in synaptic number and strength that occur during wakefulness2. Some studies examining either large neuronal populations3 or small patches of dendrites4 have found evidence consistent with the synaptic homeostasis hypothesis, but whether sleep merely functions as a permissive state or actively promotes synaptic downregulation at the scale of whole neurons is unclear. Here, by repeatedly imaging all excitatory synapses on single neurons across sleep–wake states of zebrafish larvae, we show that synapses are gained during periods of wake (either spontaneous or forced) and lost during sleep in a neuron-subtype-dependent manner. However, synapse loss is greatest during sleep associated with high sleep pressure after prolonged wakefulness, and lowest in the latter half of an undisrupted night. Conversely, sleep induced pharmacologically during periods of low sleep pressure is insufficient to trigger synapse loss unless adenosine levels are boosted while noradrenergic tone is inhibited. We conclude that sleep-dependent synapse loss is regulated by sleep pressure at the level of the single neuron and that not all sleep periods are equally capable of fulfilling the functions of synaptic homeostasis.
Phylogenomics and genetic analysis of solvent-producing Clostridium species
Authors: Jensen Rasmus O. , Schulz Frederik , Roux Simon , Klingeman Dawn M. , Mitchell Wayne P. , Udwary Daniel , Moraïs Sarah , Reynoso Vinicio , Winkler James , Nagaraju Shilpa , De Tissera Sashini , Shapiro Nicole , Ivanova Natalia , Reddy T. B. K. , Mizrahi Itzhak , Utturkar Sagar M. , Bayer Edward A. , Woyke Tanja , Mouncey Nigel J. , Jewett Michael C. , Simpson Séan D. , Köpke Michael , Jones David T. , Brown Steven D.
Published: May 2024

The genus Clostridium is a large and diverse group within the Bacillota (formerly Firmicutes), whose members can encode useful complex traits such as solvent production, gas-fermentation, and lignocellulose breakdown. We describe 270 genome sequences of solventogenic clostridia from a comprehensive industrial strain collection assembled by Professor David Jones that includes 194 C. beijerinckii, 57 C. saccharobutylicum, 4 C. saccharoperbutylacetonicum, 5 C. butyricum, 7 C. acetobutylicum, and 3 C. tetanomorphum genomes. We report methods, analyses and characterization for phylogeny, key attributes, core biosynthetic genes, secondary metabolites, plasmids, prophage/CRISPR diversity, cellulosomes and quorum sensing for the 6 species. The expanded genomic data described here will facilitate engineering of solvent-producing clostridia as well as non-model microorganisms with innately desirable traits. Sequences could be applied in conventional platform biocatalysts such as yeast or Escherichia coli for enhanced chemical production. Recently, gene sequences from this collection were used to engineer Clostridium autoethanogenum, a gas-fermenting autotrophic acetogen, for continuous acetone or isopropanol production, as well as butanol, butanoic acid, hexanol and hexanoic acid production.
Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention for acute myocardial infarction with cardiogenic shock
Authors: Lee Oh-Hyun , Heo Seok-Jae , Johnson Thomas W. , Kim Yongcheol , Cho Deok-Kyu , Kim Jung-Sun , Kim Byeong-Keuk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo , Jeong Myung Ho ,   The Investigators for KAMIR,   KAMIR-NIH Participating Sites and Investigators, Jeong Myung Ho , Ahn Tae Hoon , Seung Ki Bae , Rha Seung-Woon , Kim Hyo-Soo , Yoon Chang-Hwan , Gwon Hyeon-Cheol , Kim Chong-Jin , Yoon Junghan , Seong In-Whan , Hwang Kyung-Kuk , Chae Jei Keon , Oh Seok Kyu , Lee Jung-Hee , Chae Shung Chull , Hur Seung-Ho , Cha Kwang Soo , Hwang Jin-Yong , Kim Doo-Il , Joo Seung-Jae ,   KAMIR-V Participating Sites and Investigators, Jeong Myung Ho , Chang KiYuk , Kim Hee-Yeol , Yoo Ki-Dong , Yoo Sang-Yong , Chae Shung Chull , Hwang Jin-Yong , Kim Weon , Hur Seung Ho , Rha Seung-Woon , Nah Deuk-Young , Kim Chong-Jin , Cha Kwang Soo , Yoon Chang-Hwan , Kim Hyo-Soo , Gwon Hyeon-Cheol , Cho Jang Hyun , Park Jong-Seon , Oh Seok Kyu , Yoon Junghan , Lee Kyu-Sun , Chae Jei Keon , Rhew Jay-Young , Joo Seung-Jae , Yang Yong-Mo , Seong In-Whan , Hwang Kyung-Kuk , Kim Sang-Hyun , Kim Doo-Il , Park Yong Hwan , Kwon Sung Uk , Ahn Tae Hoon , Kim Dong-Bin , Cho Byung Ryul , Lee Seung-Uk , Bae Jang Ho , Lim Sang Yup , Kim Kee Sik , Kim Moo Hyun , Park Sang-Ho , Tak Seung Je , Woo Sung-Il , Kim Byung Ok
Published: May 2024

The benefits of intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) in the clinical context of cardiogenic shock (CS) complicating acute myocardial infarction are lacking. We aimed to investigate the impact of IVUS-guided PCI in patients with AMI and CS. From the pooled data based on a series of Korean AMI registries during 2011–2020, we identified 1418 consecutive patients who underwent PCI with second generation drug-eluting stent (DES) for AMI and CS. The primary endpoint was the 1-year rate of target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction, and ischemic-driven target lesion revascularization. In total, 294 (20.7%) and 1124 (79.3%) underwent IVUS-guided and angiography-guided PCI with second generation DES implantation, respectively. The 1-year TLF was not significantly different between groups after IPTW analysis (hazard ratio 0.93, 95% confidence interval 0.65–1.34, p = 0.70). Additionally, the adjusted landmark analysis for TLF at 30 days and between 30 days and 1 year after PCI demonstrated no significant difference between the groups. In conclusion, in patients with AMI and CS who underwent PCI with second-generation DES, IVUS-guided PCI did not improve the 1-year TLF compared with angiography-guided PCI.

Registration: URL: http://cris.nih.go.kr. KCT0000863 and KCT0008355.
Silencing Ditylenchus destructor cathepsin L-like cysteine protease has negative pleiotropic effect on nematode ontogenesis
Authors: Huang Guoqiang , Cong Ziwen , Liu Zhonglin , Chen Feng , Bravo Alejandra , Soberón Mario , Zheng Jinshui , Peng Donghai , Sun Ming
Published: May 2024

Ditylenchus destructor is a migratory plant-parasitic nematode that severely harms many agriculturally important crops. The control of this pest is difficult, thus efficient strategies for its management in agricultural production are urgently required. Cathepsin L-like cysteine protease (CPL) is one important protease that has been shown to participate in various physiological and pathological processes. Here we decided to characterize the CPL gene (Dd-cpl-1) from D. destructor. Analysis of Dd-cpl-1 gene showed that Dd-cpl-1 gene contains a signal peptide, an I29 inhibitor domain with ERFNIN and GNFD motifs, and a peptidase C1 domain with four conserved active residues, showing evolutionary conservation with other nematode CPLs. RT-qPCR revealed that Dd-cpl-1 gene displayed high expression in third-stage juveniles (J3s) and female adults. In situ hybridization analysis demonstrated that Dd-cpl-1 was expressed in the digestive system and reproductive organs. Silencing Dd-cpl-1 in 1-cell stage eggs of D. destructor by RNAi resulted in a severely delay in development or even in abortive morphogenesis during embryogenesis. The RNAi-mediated silencing of Dd-cpl-1 in J2s and J3s resulted in a developmental arrest phenotype in J3 stage. In addition, silencing Dd-cpl-1 gene expression in female adults led to a 57.43% decrease in egg production. Finally, Dd-cpl-1 RNAi-treated nematodes showed a significant reduction in host colonization and infection. Overall, our results indicate that Dd-CPL-1 plays multiple roles in D. destructor ontogenesis and could serve as a new potential target for controlling D. destructor.
Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment
Authors: Chan Wai Sze
Published: May 2024

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals—sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.
Value of turbo spin echo–based diffusion-weighted imaging in the differential diagnosis of benign and malignant solitary pulmonary lesions
Authors: Lei Qiang , Liu Lishan , Li Jianneng , Yu Kanghui , Yin Yi , Wang Jurong , Su Sulian , Song Yang , Jiang Guihua
Published: May 2024

To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)–based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE–based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann–Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = − 4.522, p < 0.001). Additionally, the ADC800, ADCtotal, and D values were all significantly lower in lung cancer than in the benign lesions (Z = − 5.054, -5.370, and -6.047, respectively, all p < 0.001), whereas the f values did not exhibit any statistically significant difference between the two groups. D had the highest area under the curve (AUC = 0.887), followed by ADCtotal (AUC = 0.844), ADC800 (AUC = 0.824), and LSR (AUC = 0.789). The LSR, ADC800, ADCtotal, and D values did not differ statistically significantly in diagnostic effectiveness. Lung DWI using TSE is feasible for differentiating SPLs. The LSR method, conventional DWI, and IVIM have comparable diagnostic efficacy for assessing SPLs.
Role of volcanism and impact heating in mass extinction climate shifts
Authors: Kaiho Kunio
Published: May 2024

This study investigates the mechanisms underlying the varied climate changes witnessed during mass extinctions in the Phanerozoic Eon. Climate shifts during mass extinctions have manifested as either predominant global cooling or predominant warming, yet the causes behind these occurrences remain unclear. We emphasize the significance of sedimentary rock temperature in comprehending these climate shifts. Our research reveals that low-temperature heating of sulfide leads to global cooling through the release of sulfur dioxide (SO2), while intermediate-temperature heating of hydrocarbons and carbonates releases substantial carbon dioxide (CO2), contributing to global warming. High-temperature heating additionally generates SO2 from sulfate, further contributing to global cooling. Different degrees of contact heating of the host rock can lead to different dominant volatile gas emissions, crucially driving either warming or cooling. Moreover, medium to high-temperature shock-heating resulting from asteroid impacts produces soot from hydrocarbons, also contributing to global cooling. Large-scale volcanic activity and asteroid impacts are both events that heat rocks, emitting the same gases and particles, causing climate changes. The findings elucidate the critical role of heating temperature and heating time in understanding major climate changes during mass extinctions.
Sexual experience in patients with coronary heart disease: a descriptive phenomenological study
Authors: Zhang Fengpei , Li Yachai , Shi Zhili , Wang Aiping
Published: May 2024

Sex is an essential part of life and is a basic demand for human beings. Coronary heart disease can have an impact on patients’ sexual lives; however, not much attention has been paid to it in China, and few studies have been conducted on this topic. Therefore, this study used a qualitative approach to understand the sexual experience of patients after the illness, thus laying the foundation for the development of relevant measures. Semi-structured interviews were conducted with 14 patients. Descriptive phenomenological methods were employed to collect data and explore the sexual experience of patients with coronary heart disease. A total of 4 thematic groups, 9 themes, and 23 subthemes were extracted. The four thematic groups were independent and cross-influenced. In these groups, alterations in the sexual experience, including the change in sexual physiology and psychological state, were affected by the lack of knowledge, age, disease, and other factors. Furthermore, the patient’s perception of sexuality affected the quality of sexual life after the illness. The sexual experience of patients with coronary heart disease and its influencing factors, such as age, disease factors, and lack of related knowledge, were described. The findings are expected to aid in formulating targeted and personalized intervention measures.
Occupancy dynamics of free ranging American mink (Neogale vison) in Greece
Authors: Bakaloudis Dimitrios E. , Thoma Charalambos T. , Makridou Konstantina N. , Kotsonas Evangelos G.
Published: May 2024

Identifying the environmental factors that determine the occurrence of invasive species is essential in defining and implementing effective control campaigns. Here, we applied multi-season occupancy models to analyze American mink (Neogale vison) track data collected using 121 floating rafts, as a function of factors occurring at multiple spatial scales. Our overall aim was to identify those factors that determine the use, colonization or abandonment of rafts by free ranging individuals found in western Macedonia, Greece. We found that increasing values of shrubs and rock cover at the micro-habitat scale were positively associated with the species’ probability of raft use, as was the density of medium-sized rivers at the landscape scale. Colonization was found to increase with increasing amounts of shrub and reed cover; however, both variables were not informative. Conversely, the distance from the nearest fur farm was highly informative in predicting raft abandonment by the species. Effective control actions may require removal by trapping along rocky or densely vegetated riverbanks or lake shores located in the vicinity of the established fur farms in the area. Habitat management, although possible, may be difficult to implement due to the ability of the species to adapt. Finally, fur farms should maximize security and establish an early warning and rapid eradication system in case of future escapes.
Understanding the genomic heterogeneity of North African Imazighen: from broad to microgeographical perspectives
Authors: Vilà-Valls Laura , Abdeli Amine , Lucas-Sánchez Marcel , Bekada Asmahan , Calafell Francesc , Benhassine Traki , Comas David
Published: May 2024

The strategic location of North Africa has led to cultural and demographic shifts, shaping its genetic structure. Historical migrations brought different genetic components that are evident in present-day North African genomes, along with autochthonous components. The Imazighen (plural of Amazigh) are believed to be the descendants of autochthonous North Africans and speak various Amazigh languages, which belong to the Afro-Asiatic language family. However, the arrival of different human groups, especially during the Arab conquest, caused cultural and linguistic changes in local populations, increasing their heterogeneity. We aim to characterize the genetic structure of the region, using the largest Amazigh dataset to date and other reference samples. Our findings indicate microgeographical genetic heterogeneity among Amazigh populations, modeled by various admixture waves and different effective population sizes. A first admixture wave is detected group-wide around the twelfth century, whereas a second wave appears in some Amazigh groups around the nineteenth century. These events involved populations with higher genetic ancestry from south of the Sahara compared to the current North Africans. A plausible explanation would be the historical trans-Saharan slave trade, which lasted from the Roman times to the nineteenth century. Furthermore, our investigation shows that assortative mating in North Africa has been rare.
Analysis of deformation mechanism of rainfall-induced landslide in the Three Gorges Reservoir Area: Piansongshu landslide
Authors: Wang Hui , Zou Jianhua , Wang Xinghua , Lv Peng , Tan Zefu , Cheng Longfei , Wei Qiang , Qin Binli , Guo Zhengchao
Published: May 2024

The Three Gorges Reservoir Area (TGRA) is characterized by unique geological features that increase its susceptibility to landslides. These slopes are especially prone to destabilization when influenced by external triggers like rainfall. This research focuses on the Piansongshu landslide within the TGRA, aiming at unraveling the complex internal deformation mechanisms of landslides triggered by rainfall and providing critical insights for their prevention and mitigation. The study begins with on-site geological surveys to meticulously examine the macroscopic signs and mechanisms of deformation. It then utilizes the GeoStudio numerical simulation software to assess the landslide's stability, focusing on the changes in internal seepage fields and stability under various rainfall scenarios. Results indicate that continuous rainfall leads to the formation of a temporary saturation zone on the slope, which gradually deepens. In regions with more pronounced deformation, the infiltration line at the leading edge of accumulation notably protrudes towards the surface. Notably, the stability coefficient of the secondary shear surface of the landslide fluctuates more significantly than that of the primary sliding surface. Higher rainfall intensity and longer duration are positively correlated with a more pronounced decrease in stability coefficients. The impact on stability also varies across different rainfall patterns. As rainfall infiltrates over time, the slope's safety factor gradually decreases. This reduction continues even post-rainfall, indicating a delayed restoration period before stability returns to a safe level. These results yield valuable data for forecasting and mitigating landslides.
Molecular characterization of similar Hb Lepore Boston-Washington in four Chinese families using third generation sequencing
Authors: Zhuang Jianlong , Zhang Na , Zheng Yu , Jiang Yuying , Chen Yu’e , Mao Aiping , Chen Chunnuan
Published: May 2024

Hemoglobin (Hb) Lepore is a rare deletional δβ-thalassemia caused by the fusion between delta-beta genes, and cannot be identified by traditional thaltassemia gene testing technology. The aim of this study was to conduct molecular diagnosis and clinical analysis of Hb Lepore in four unrelated Chinese families using third generation sequencing. Decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and an abnormal Hb band were observed in the probands of the four families. However, no common α and β-thalassemia variants were detected in the enrolled families using polymerase chain reaction-reverse dot blot hybridization based traditional thalassemia gene testing. Further third-generation sequencing revealed similar Hb Lepore-Boston-Washington variants in all the patients, which were resulted from partial coverage of the HBB and HBD globin genes, leading to the formation of a delta-beta fusion gene. Specific gap-PCR and Sanger sequencing confirmed that all the patients carried a similar Hb Lepore-Boston-Washington heterozygote. In addition, decreased levels of MCH and Hb A2 were observed in the proband’s wife of family 2, an extremely rare variant of Hb Nanchang (GGT > AGT) (HBA2:c.46G > A) was identified by third-generation sequencing and further confirmed by Sanger sequencing. This present study was the first to report the similar Hb Lepore-Boston-Washington in Chinese population. By combining the utilization of Hb capillary electrophoresis and third-generation sequencing, the screening and diagnosis of Hb Lepore can be effectively enhanced.
An adaptive Bayesian approach for improved sensitivity in joint monitoring of mean and variance using Max-EWMA control chart
Authors: Zaagan Abdullah A. , Noor-ul-Amin Muhammad , Khan Imad , Iqbal Javed , Hussain Saddam
Published: May 2024

This article introduces an adaptive approach within the Bayesian Max-EWMA control chart framework. Various Bayesian loss functions were used to jointly monitor process deviations from the mean and variance of normally distributed processes. Our study proposes the mechanism of using a function-based adaptive method that picks self-adjusting weights incorporated in Bayesian Max-EWMA for the estimation of mean and variance. This adaptive mechanism significantly enhances the effectiveness and sensitivity of the Max-EWMA chart in detecting process shifts in both the mean and dispersion. The Monte Carlo simulation technique was used to calculate the run-length profiles of different combinations. A comparative performance analysis with an existing chart demonstrates its effectiveness. A practical example from the hard-bake process in semiconductor manufacturing is presented for practical context and illustration of the chart settings and performance. The empirical results showcase the superior performance of the Adaptive Bayesian Max-EWMA control chart in identifying out-of-control signals. The chart’s ability to jointly monitor the mean and variance of a process, its adaptive nature, and its Bayesian framework make it a useful and effective control chart.