bluuebunny/crossref_metadata_2025 huggingface dataset:
Processos de ensino e aprendizagem de Matemática em um formato híbrido na educação superior
Authors: Bertoluci Evandro Antonio , De Souza Aguinaldo Robinson
Published: June 2018

Neste artigo apresentamos os resultados de uma investigação em que buscamos identificar e analisar as contribuições de práticas pedagógicas virtuais e presenciais desenvolvidas por professores mediadores de Matemática de um curso superior de tecnologia da área de Gestão Empresarial, oferecido na modalidade de educação a distância, para a construção de conhecimentos matemáticos pelos alunos. A investigação realizada se enquadrou na vertente qualitativa de pesquisa; buscamos identificar e analisar os processos de ensino e aprendizagem de conteúdos matemáticos, ocorridos no âmbito do curso, em uma turma de um polo de apoio presencial. No referencial teórico consideramos os seguintes tópicos: aspectos da aprendizagem matemática à distância; os ambientes virtuais de aprendizagem; as abordagens pedagógicas adotadas em processos formativos; a formatação de cursos em ambientes virtuais; os processos de mediação pedagógica em novos paradigmas; a questão da evasão; os problemas relacionados à gestão, controle e avaliação de cursos a distância e a formação de comunidades de aprendizagem em cursos híbridos. Os resultados indicaram: as contribuições das práticas pedagógicas específicas dos professores mediadores de Matemática do curso para a construção de conhecimentos matemáticos; os diferentes conhecimentos matemáticos construídos pelos alunos, considerando a abordagem pedagógica adotada e as características das tecnologias utilizadas; os fatores que influenciaram a evasão dos alunos ao longo do semestre. Os resultados demonstraram, também: que é de fundamental importância que os professores mediadores tenham formação específica na área ou em áreas afins das disciplinas em que atuam; que os processos de ensino e aprendizagem de Matemática na modalidade de educação a distância podem ser bem-sucedidos se forem adotadas propostas híbridas de educação, com a integração de abordagens e tecnologias presenciais e online, selecionadas de forma minuciosa de tal forma que se complementem.
O PLANO MUNICIPAL DE EDUCAÇÃO DE DOURADOS-MS: POLÍTICA, GESTÃO E PARTICIPAÇÃO
Authors: De Miranda Aranda Maria Alice , Perboni Fábio , Rodrigues Evally Solaine de Souza
Published: June 2018

O presente artigo trata do Plano Municipal de Educação (PME) de Dourados no estado de Mato Grosso do Sul (MS), analisando a sua organização enquanto documento balizador da política e da gestão educacional, cujo princípio fundante para sua materialização é o principio da participação. No tempo presente, torna-se indubitável ter como objeto de estudo os Planos de Educação, considerando ser preceito legal no Plano Nacional de Educação (2014-2024) que especifica no Artigo 8º a exigência de elaboração e/ou adequação dos Planos Municipais de Educação no prazo de um ano, contado da publicação da Lei n° 13.005, de 25 de julho de 2014, que aprovou o Plano Nacional de Educação (2014-2024). Assim, dando continuidade a pesquisa recentemente concluída intitulada “O Conselho Municipal de Educação (CME) no Brasil e a Qualidade Socialmente Referenciada do Ensino Público” – Chamada Universal – MCTI/CNPq Nº 14/2014 – que envolveu cinco Universidades Públicas e teve como propósito indagar a participação dos CMEs na elaboração dos PMEs, esta em voga a Pesquisa “Monitoramento dos Planos Municipais de Educação no estado do MS”, cadastrada na Pró Reitoria de Pesquisa da Universidade Federal da Grande Dourados. Em síntese, enquanto Documento, o PME em foco pretende ser uma política educacional de caráter estatal, fundamentado na gestão democrática da educação, portanto, tem a participação como princípio fundante para sua realização.
Marketing viral político dentro del esquema Ponzi
Authors: Vega Fernández Eduardo
Published: June 2018

In a Spain so immersed in Globalization, or rather Globalism, and far from economic autarchy of those long decades of the twentieth century, we are not giving importance to advertising and marketing, when it is more than important to conceive the magnitude of propaganda and political communication. Businesses and multinationals offer us visible, tangible products. However, nowadays, politics presents proposals that cannot be perceived in the same way as in trade, leaving the citizens far from these political decisions, their complete comprehension and understanding of their development and its reason why. A product and a trademark can spark a complete indifference and dispensability in people, but politics and the economy are issues of great importance in our lives. Although we are indifferent, they still mark our future. This fact will be the one that provides us with a job, allows us to start a business, provides health and education, public safety, public administration and a long list of essential issues of our lives. It is therefore more than important for us to make decisions in this area, away from lying, partial and incomplete information from the media, nor false truths. It is essential to conceive this new concept of political viral marketing within the Ponzi scheme, which enables a lie to be promoted to keep a party and its representative in government office, destroying the socioeconomic and political perspectives that we had trusted. Ponzi praises a leader and his political group in power, thanks to the virus unknowingly released by the vox populi, creating a popular pyramid that will fall when people discover the propaganda and lies disseminated about this political product that has ended up becoming a new immovable government of position.
El impacto del mensaje corporativo en la Web 2.0
Authors: Solís Rafael , Sánchez Joaquín
Published: June 2018

Although the proliferation of platforms 2.0 is a new kind of relationship with current and potential consumers, it is still not possible to assess their reach and influence in the perception of corporate messages. This research aims to find out the value of different platforms 2.0 from the perspective of corporate communication. The study focuses on the microblog Twitter as the empirical case, where comments from internet users about eight corporate campaigns are analysed. The structure of pre-/post-test analysis of the research has established how feelings of microblog users evolve after receiving the impact of a 2.0 campaign. The results obtained show that corporate messages have a positive impact on the company’s assessment. This opens new ways of interaction with users and other interest groups.
Phylogeography and population genetics of Macronycteris commersonii s.s. (Chiroptera: Hipposideridae), an endemic Malagasy bat
Authors: Rakotoarivelo Andrinajoro R , Goodman Steven M , Schoeman M Corrie , Willows-Munro Sandi
Published: June 2018

Macronycteris commersonii (Hipposideridae), a bat species endemic to Madagascar, is widespread across the island, utilising open woodland, degraded habitats, and forested areas from sea level to 1325 m. We investigated the fine-scale phylogeographic history and relationships of populations occurring in the western half of the island using sequence data from two mitochondrial DNA regions and extensive geographical sampling. Our results indicated a highly supported monophyletic group of M. commersonii, in which the Northern Madagascar Clade C formed a single monophyletic clade. The most recent common ancestor of M. commersonii was dated to 0.82 million years ago (mid-Pleistocene). Population expansion events were inferred for Clade B from approximately 130,000 to 70,000 years BP. Bayesian clustering and AMOVA analyses inferred week population genetic structure and sequence data indicated that genetic subdivisions do not support an isolation-by-distance model. Lineage dispersal, genetic divergence, and expansion events of M. commersonii were likely to be associated with Pleistocene climate fluctuations. Our data suggested that the northern and the central western regions of Madagascar may have acted as refugia for this species during periods of cooler and drier climate conditions associated with the Pleistocene.
Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress
Authors: Inoue Ran , Abdou Kareem , Hayashi-Tanaka Ayumi , Muramatsu Shin-ichi , Mino Kaori , Inokuchi Kaoru , Mori Hisashi
Published: June 2018

Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.
The functional organization of descending sensory-motor pathways in Drosophila
Authors: Namiki Shigehiro , Dickinson Michael H , Wong Allan M , Korff Wyatt , Card Gwyneth M
Published: June 2018

In most animals, the brain controls the body via a set of descending neurons (DNs) that traverse the neck. DN activity activates, maintains or modulates locomotion and other behaviors. Individual DNs have been well-studied in species from insects to primates, but little is known about overall connectivity patterns across the DN population. We systematically investigated DN anatomy in Drosophila melanogaster and created over 100 transgenic lines targeting individual cell types. We identified roughly half of all Drosophila DNs and comprehensively map connectivity between sensory and motor neuropils in the brain and nerve cord, respectively. We find the nerve cord is a layered system of neuropils reflecting the fly’s capability for two largely independent means of locomotion -- walking and flight -- using distinct sets of appendages. Our results reveal the basic functional map of descending pathways in flies and provide tools for systematic interrogation of neural circuits.
Optogenetic dissection of descending behavioral control in Drosophila
Authors: Cande Jessica , Namiki Shigehiro , Qiu Jirui , Korff Wyatt , Card Gwyneth M , Shaevitz Joshua W , Stern David L , Berman Gordon J
Published: June 2018

In most animals, the brain makes behavioral decisions that are transmitted by descending neurons to the nerve cord circuitry that produces behaviors. In insects, only a few descending neurons have been associated with specific behaviors. To explore how descending neurons control an insect’s movements, we developed a novel method to systematically assay the behavioral effects of activating individual neurons on freely behaving terrestrial D. melanogaster. We calculated a two-dimensional representation of the entire behavior space explored by these flies, and we associated descending neurons with specific behaviors by identifying regions of this space that were visited with increased frequency during optogenetic activation. Applying this approach across a large collection of descending neurons, we found that (1) activation of most of the descending neurons drove stereotyped behaviors, (2) in many cases multiple descending neurons activated similar behaviors, and (3) optogenetically activated behaviors were often dependent on the behavioral state prior to activation.
The human leukemia virus HTLV-1 alters the structure and transcription of host chromatin in cis
Authors: Melamed Anat , Yaguchi Hiroko , Miura Michi , Witkover Aviva , Fitzgerald Tomas W , Birney Ewan , Bangham Charles RM
Published: June 2018

Chromatin looping controls gene expression by regulating promoter-enhancer contacts, the spread of epigenetic modifications, and the segregation of the genome into transcriptionally active and inactive compartments. We studied the impact on the structure and expression of host chromatin by the human retrovirus HTLV-1. We show that HTLV-1 disrupts host chromatin structure by forming loops between the provirus and the host genome; certain loops depend on the critical chromatin architectural protein CTCF, which we recently discovered binds to the HTLV-1 provirus. We show that the provirus causes two distinct patterns of abnormal transcription of the host genome in cis: bidirectional transcription in the host genome immediately flanking the provirus, and clone-specific transcription in cis at non-contiguous loci up to >300 kb from the integration site. We conclude that HTLV-1 causes insertional mutagenesis up to the megabase range in the host genome in >104 persistently-maintained HTLV-1+ T-cell clones in vivo.
RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs
Authors: McClintock Mark A , Dix Carly I , Johnson Christopher M , McLaughlin Stephen H , Maizels Rory J , Hoang Ha Thi , Bullock Simon L
Published: June 2018

Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition of transported ribonucleoprotein particles (RNPs) and the regulation of their movement are poorly understood. We have reconstituted microtubule minus end-directed transport of mRNAs using purified components. A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin, thus defining a minimal transport-competent RNP. Unexpectedly, the RNA is required for robust activation of dynein motility. We show that a cis-acting RNA localisation signal promotes the interaction of Egl with BicD, which licenses the latter protein to recruit dynein and dynactin. Our data support a model for BicD activation based on RNA-induced occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor protein assemblies by cargoes is an attractive mechanism for regulating intracellular transport.
NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity
Authors: Arora Gunjan , Hart Geoffrey T , Manzella-Lapeira Javier , Doritchamou Justin YA , Narum David L , Thomas L Michael , Brzostowski Joseph , Rajagopalan Sumati , Doumbo Ogobara K , Traore Boubacar , Miller Louis H , Pierce Susan K , Duffy Patrick E , Crompton Peter D , Desai Sanjay A , Long Eric O
Published: June 2018

Antibodies acquired naturally through repeated exposure to Plasmodium falciparum are essential in the control of blood-stage malaria. Antibody-dependent functions may include neutralization of parasite–host interactions, complement activation, and activation of Fc receptor functions. A role of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in protection from malaria has not been established. Here we show that IgG isolated from adults living in a malaria-endemic region activated ADCC by primary human NK cells, which lysed infected red blood cells (RBCs) and inhibited parasite growth in an in vitro assay for ADCC-dependent growth inhibition. RBC lysis by NK cells was highly selective for infected RBCs in a mixed culture with uninfected RBCs. Human antibodies to P. falciparum antigens PfEMP1 and RIFIN were sufficient to promote NK-dependent growth inhibition. As these results implicate acquired immunity through NK-mediated ADCC, antibody-based vaccines that target bloodstream parasites should consider this new mechanism of action.
A reference cytochrome c oxidase subunit I database curated for hierarchical classification of arthropod metabarcoding data
Authors: Richardson Rodney T. , Bengtsson-Palme Johan , Gardiner Mary M. , Johnson Reed M.
Published: June 2018

Metabarcoding is a popular application which warrants continued methods optimization. To maximize barcoding inferences, hierarchy-based sequence classification methods are increasingly common. We present methods for the construction and curation of a database designed for hierarchical classification of a 157 bp barcoding region of the arthropod cytochrome c oxidase subunit I (COI) locus. We produced a comprehensive arthropod COI amplicon dataset including annotated arthropod COI sequences and COI sequences extracted from arthropod whole mitochondrion genomes, the latter of which provided the only source of representation for Zoraptera, Callipodida and Holothyrida. The database contains extracted sequences of the target amplicon from all major arthropod clades, including all insect orders, all arthropod classes and Onychophora, Tardigrada and Mollusca outgroups. During curation, we extracted the COI region of interest from approximately 81 percent of the input sequences, corresponding to 73 percent of the genus-level diversity found in the input data. Further, our analysis revealed a high degree of sequence redundancy within the NCBI nucleotide database, with a mean of approximately 11 sequence entries per species in the input data. The curated, low-redundancy database is included in the Metaxa2 sequence classification software (http://microbiology.se/software/metaxa2/). Using this database with the Metaxa2 classifier, we performed a cross-validation analysis to characterize the relationship between the Metaxa2 reliability score, an estimate of classification confidence, and classification error probability. We used this analysis to select a reliability score threshold which minimized error. We then estimated classification sensitivity, false discovery rate and overclassification, the propensity to classify sequences from taxa not represented in the reference database. Our work will help researchers design and evaluate classification databases and conduct metabarcoding on arthropods and alternate taxa.
Racial and Ethnic Disparities in Fentanyl and Polysubstance Overdose Deaths
Authors: Zhu David T.
Published: November 2024

This cross-sectional study describes US overdose death patterns for fentanyl and fentanyl combined with opioids, heroin, cocaine, methamphetamine, or benzodiazepines by race and ethnicity from 2010 to 2022.
Gender, Health, and Mortality
Authors: Smith‐Johnson Madeline , Gorman Bridget
Published: November 2024

Across all national contexts, women have a mortality advantage over men. Women tend to live with more chronic disabling health conditions, while men tend to have more fatal health outcomes. These trends depend on age and stage of the life course. A growing body of scholarship also shows that transgender adults have some health and mortality disadvantages compared to cisgender adults. Gendered patterns in health depend on the epidemiological and social context of a particular society and are produced by a combination of biological, behavioral, and social or structural factors. Gendered patterns change in interaction with other statuses such as race, ethnicity, and sexual orientation, reflecting the importance of specific intersectional positions in shaping health status.
Constructing an Active Sulfur‐Vacancy‐Rich Surface for Selective *CH3‐CH3 Coupling in CO2‐to‐C2H6 Conversion With 92% Selectivity
Authors: Yang Xiaonan , Ren Liteng , Chen Zhiheng , Li Huiquan , Yuan Yupeng
Published: November 2024

To achieve high selectivity in photocatalytic CO2 reduction to C2+ products, increasing the number of CO2 adsorption sites and lowering the energy barriers for key intermediates are critical. A ZnIn2S4 (ZIS)/MoO3‐x (Z‐M) photocatalyst is presented, in which plasmonic MoO3‐x generates hot electrons, creating a multielectron environment in ZIS that facilitates efficient C─C coupling reactions. Density functional theory (DFT) calculations reveal that MoO3‐x reduces the formation energy of sulfur vacancies (SV) in ZIS, thereby enhancing CO2 adsorption and activation. The SV‐rich surface lowers the energy barrier for forming HCOO* to −0.33 eV whereas the energy barrier for forming *COOH is 0.77 eV. Successive hydrogenation of HCOO* leads to *CH2, which converts to *CH3 with an energy barrier of −0.63 eV. The energy barrier for *CH3‐CH3 coupling is 0.54 eV, which is lower than the 0.73 eV for *CH2‐CH2 coupling to form *C2H4. Thus, Z‐M preferentially produces C2H6 over C2H4. Under visible light, Z‐M achieves a CO2‐to‐C2H6 conversion rate of 467.3 µmol g−1 h−1 with 92.0% selectivity. This work highlights the dual role of plasmonic photocatalysts in enhancing CO2 adsorption and improving C2+ production in CO2 reduction.
Bone‐Induced Nanocomposite Coating with a “Sandwich” Structure
Authors: Guan Yushuang , Zou Guoming , osman Henigul , Zhang Dong , Zhou Tianyou , Cui Wenguo , Wang Yingbo
Published: November 2024

Infection‐induced bone defects present significant challenges in clinical bone regeneration, frequently leading to poor bone induction, recurring infections, and complications such as pain and chronic inflammation. This study introduces a novel Ti/Lignin‐Ag@PLL composite coating with a “sandwich” structure, designed to integrate pro‐adhesion, photothermal‐photodynamic antibacterial, and osteogenic properties. The Ti/Lignin‐Ag@PLL composite coating is fabricated using self‐assembly technology, in which Ag+ is reduced to silver nanoparticles (Ag‐NPs) by lignin, followed by Polylysine (PLL) grafting. Photothermal conversion efficiency is evaluated under near‐infrared (NIR) laser irradiation, while antibacterial activity is tested against E. coli and S. aureus. Biocompatibility is also assessed using vascular endothelial cells (VECs) and osteoblasts (OBs). The results indicate that the Ti/Lignin‐Ag@PLL coating demonstrates a 31% photothermal conversion efficiency and nearly 100% antibacterial efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) under NIR irradiation for 10 min. Without irradiation, the antibacterial rates are 85% and 94%, respectively, after 24 h. Additionally, the coating significantly promotes cell adhesion, proliferation, and osteogenesis, as evidenced by the upregulation of Runx2 and Collagen I. This study uniquely contributes to the development of a multifunctional composite coating that effectively combines robust antibacterial properties with enhanced osteogenic potential, offering a promising solution for bone tissue repair and infection prevention.
Glycerol Vapor Assisted Cu Direct Bonding: Implications for 3D Semiconductor Packaging
Authors: Na Jeehoo , Lee Eunhye , Park Kyung‐Ho , Lee Dongwoo , Lee Tae‐Ik
Published: November 2024

As the scaling down of semiconductor devices reaches its physical limits, 3D stacking packaging technology is emerging as a new miniaturization solution. Among the various 3D packaging technologies, Cu direct bonding is widely adopted due to copper's excellent electrical conductivity and the absence of intermetallic compounds for solder bumps. Since copper readily undergoes oxidation, technologies that prevent Cu surface oxidation during Cu direct bonding are essential. However, current research suggests that the methods require additional pretreatment processes, which demand high costs. In this study, a Cu direct bonding method utilizing glycerol vapor is developed to effectively streamline the pretreatment steps. The potential of glycerol as a reducing agent and antioxidant for Cu is demonstrated using a silicon die sample with a size of 10  ×  10 mm2, verified through the X‐ray photoelectron spectroscopy. The Cu direct bonding for 3D semiconductor packaging is successfully performed under glycerol vapor atmosphere, without any plasma pretreatment. The cross‐section of the bonded specimens is examined by scanning electron microscopy, and mechanical reliability is assessed by die shear testing.
Magnetic Hercules Swarm for Precise and Effective Deep Biofilm Eradication
Authors: Xu Yunqi , Wang Kang , Lou Congcong , Wang Qin , Gong Xinglong , Fang Qunling , Luo Tianzhi , Xuan Shouhu
Published: November 2024

Over the past decade, significant advancements in micro‐nano robots have enabled non‐invasive operations in hazardous, confined environments, particularly targeting persistent bacterial biofilms in hard‐to‐reach areas. However, many of these robots are limited by poor magnetic properties, hindering their effectiveness against biofilms. This study proposes a novel strategy using a swarm with strong magnetic effects (Hercules swarm) combined with near‐infrared (NIR) light for effective biofilm eradication. Carbonyl iron particles coated with polydopamine (CI@PDA), averaging ≈3 µm in diameter, demonstrate clustering and significant magneto‐force under a rotating magnetic field due to their large magnetic saturation. This enables the Hercules swarm to achieve rapid delivery (100 mm s−1), efficient cargo transport (carrying twice its own weight), and effective catheter clearance (1 mm min−1). The controllable motion and high photothermal activity enable precise biofilm eradication without toxic agents. The aggregation of magnetic particles into chains and their rotation are explored by improved particle dynamic model. Simulations also reveal enhanced fluid convection and mechanical pressure around the particle chain. Due to its easy operation, straightforward controllability, and environmental compatibility, the magnetic Hercules swarm emerges as a promising treatment modality for eliminating biofilms entrenched within intricate, narrow, and convoluted medical implants or industrial conduits.
Regio‐ and Diastereoselective One‐pot Double Cascade Hybrid Formation/[3+3] Spirocyclization for the Synthesis of 3‐Spiropiperidines Under Phase Transfer Conditions
Authors: Di Mola Antonia , Sadeq Mousavi Mohammad , Simeone Lorenzo , Pierri Giovanni , Massa Antonio
Published: November 2024

Herein, we report an efficient approach to synthesizing hybrid 3‐spiropiperidine heterocycles that incorporate both 3‐isochromanone and 3‐isoindolinone units through a one‐pot, double cascade reaction facilitated by an economical K2CO3/TBAB catalytic system. By examining the nucleophilicity of the lactone 3‐isochromanone, we developed a cascade reaction pathway that first generates a bi‐nucleophilic hybrid intermediate, which then undergoes [3+3] spirocyclization with α,β‐unsaturated aldehydes. The regioselectivity of the spirocyclization strongly depends on the substitution pattern of lactam ring.The process exhibits high diastereoselectivity, even with the formation of three or four stereocenters, including two contiguous tetra‐substituted carbons. These sequential cascade reactions were successfully scaled up, and the subsequent reactivity was readily analyzed, enabling the transformation of existing functional groups into valuable new functionalities.
Endosomal Trafficking Bypassed by the RAB5B‐CD109 Interplay Promotes Axonogenesis in KRAS‐Mutant Pancreatic Cancer
Authors: Zhang Dingwen , Luo Yuming , Lin Yan , Fang Zhou , Zheng Hanhao , An Mingjie , Xie Qingyu , Wu Zhuo , Yu Chao , Yang Jiabin , Yu Min , Chen Changhao , Chen Rufu
Published: November 2024

Perineural invasion (PNI) represents a unique biological feature associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC), especially in the presence of KRAS mutations. Extracellular vesicle (EV)‐packaged circular RNAs (circRNAs) function as essential mediators of tumor microenvironment communication, triggering PDAC cell invasion and distant metastasis. However, the regulatory mechanisms of EV‐packaged circRNAs in the PNI of KRAS‐mutant PDAC have not yet been elucidated. Herein, a KRASG12D mutation‐responsive EV‐packaged circRNA, circPNIT, which positively correlated with PNI in PDAC patients is identified. Functionally, KRASG12D PDAC‐derived EV‐packaged circPNIT promoted axonogenesis and PNI both in vitro and in vivo. Mechanistically, the circPNIT‐mediated Rab5B‐CD109 interplay bypassed traditional endosomal trafficking to anchor Rab5B to the lipid rafts of multivesicular bodies and packaged circPNIT into CD109+ EVs. Subsequently, CD109+ EVs delivered circPNIT to neurons by binding to TRPV1 and facilitating DSCAML1 transcription‐induced axonogenesis, which in turn enhanced the PNI by activating the GFRα1/RET pathway. Importantly, circPNIT‐loaded CD109+ EVs are established to dramatically promote PNI in a KRASG12D/+ Trp53R172H/+ Pdx‐1‐Cre mouse model. Collectively, the findings highlight the mechanism underlying how EV‐packaged circRNAs mediate the PNI of KRAS‐mutant PDAC cells through the Rab5B endosomal bypass, identifying circPNIT as an effective target for the treatment of neuro‐metastatic PDAC.
HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS
Authors: Qin Chaoying , Gong Shasha , Liang Ting , Zhang Zhenbo , Thomas Jessie , Deng Janice , Liu Yaguang , Hu Peiqing , Zhu Bi , Song Shujie , Ortiz Marisol Fernández , Ikeno Yuji , Wang Exing , Lechleiter James , Weintraub Susan T. , Bai Yidong
Published: November 2024

Oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) are key bioenergetics pathways. The machineries for both processes are localized in mitochondria. Secondary OXPHOS defects have been documented in patients with primary FAO deficiencies, and vice versa. However, the underlying mechanisms remain unclear. Intrigued by the observations that regulation of supercomplexes (SCs) assembly in a mouse OXPHOS deficient cell line and its derivatives is associated with the changes in lipid metabolism, a proteomics analysis is carried out and identified mitochondrial trifunctional protein (MTP) subunit alpha (hydroxyacyl‐CoA dehydrogenase trifunctional multienzyme complex subunit alpha, HADHA) as a potential regulatory factor for SCs assembly. HADHA‐Knockdown cells and mouse embryonic fibroblasts (MEFs) derived from HADHA‐Knockout mice displayed both reduced SCs assembly and defective OXPHOS. Stimulation of OXPHOS induced in cell culture by replacing glucose with galactose and of lipid metabolism in mice with a high‐fat diet (HFD) both exhibited increased HADHA expression. HADHA Heterozygous mice fed with HFD showed enhanced steatosis associated with a reduction of SCs assembly and OXPHOS function. The results indicate that HADHA participates in SCs assembly and couples FAO and OXPHOS.
Epigenetic Activation of the CMTM6‐IGF2BP1‐EP300 Positive Feedback Loop Drives Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma
Authors: Zhu Ying‐Qin , Huang Yue , Shi Yin‐Hao , Huang Chen‐Song , Zhao Guang‐Yin , Liu Zhi‐De , Ma Ming‐Jian , Ye Jing‐Yuan , Xu Xiang , Liu Qi , Huang Xi‐Tai , Wang Jie‐Qin , Xu Qiong‐Cong , Yin Xiao‐Yu
Published: November 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis. Gemcitabine‐based chemotherapy has emerged as a first‐line treatment for PDAC. However, the development of gemcitabine resistance often results in therapeutic failure. In order to uncover the underlying mechanisms of gemcitabine resistance, gemcitabine‐resistant PDAC cell lines and patient‐derived xenograft (PDX) models are established and subjected to RNA sequencing. It is found that CMTM6 is closely related to gemcitabine resistance in PDAC. Multi‐omics analysis revealed that EP300‐mediated H3K27ac modification is involved in the transcriptional activation of CMTM6, which maintains IGF2BP1 expression by preventing its ubiquitination. The m6A reader IGF2BP1 stabilizes the EP300 and MYC mRNAs by recognizing m6A modifications, forming a positive feedback loop that enhances tumor stemness and ultimately contributes to PDAC resistance. The combined application of the EP300 inhibitor inobrodib and gemcitabine exerts a synergistic effect on PDAC. Overall, these findings reveal that the EP300–CMTM6–IGF2BP1 positive feedback loop facilitates gemcitabine resistance via epigenetic reprogramming and the combined use of inobrodib and gemcitabine represents a promising strategy for overcoming chemoresistance in PDAC, warranting further investigation in clinical trials.
Sonogenetics in the Treatment of Chronic Diseases: A New Method for Cell Regulation
Authors: Zhu Mingrui , Fang Yan , Sun Yikang , Li Shaoyue , Yu Jifeng , Xiong Bing , Wen Congjian , Zhou Boyang , Huang Bin , Yin Haohao , Xu Huixiong
Published: November 2024

Sonogenetics is an innovative technology that integrates ultrasound with genetic editing to precisely modulate cellular activities in a non‐invasive manner. This method entails introducing and activating mechanosensitive channels on the cell membrane of specific cells using gene delivery vectors. When exposed to ultrasound, these channels can be manipulated to open or close, thereby impacting cellular functions. Sonogenetics is currently being used extensively in the treatment of various chronic diseases, including Parkinson's disease, vision restoration, and cancer therapy. This paper provides a comprehensive review of key components of sonogenetics and focuses on evaluating its prospects and potential challenges in the treatment of chronic disease.
Precise Regulation Strategy for Fluorescence Wavelength of Aggregation‐Induced Emission Carbon Dots
Authors: Ding Liu , Jin Xilang , Gao Yuchong , Kang Shouwang , Bai Haiyan , Ma Xuehao , Ai Taotao , Zhou Hongwei , Chen Weixing
Published: November 2024

Aggregation‐induced emission (AIE) carbon dot (CDs) in solid state with tunable multicolor emissions have sparked significant interest in multidimensional anti‐counterfeiting. However, the realization of solid‐state fluorescence (SSF) by AIE effect and the regulation of fluorescence wavelength in solid state is a great challenge. In order to solve this dilemma, the AIE method to prepare multi‐color solid‐state CDs with fluorescence wavelengths ranging from bright blue to red emission is employed. Specifically, by using thiosalicylic acid and carbonyl hydrazine as precursors, the fluorescence wavelength can be accurately adjusted by varying the reaction temperature from 150 to 230 °C or changing the molar ratio of the precursors from 1:1 to 1:2. Structural analysis and theoretical calculations consistently indicate that increasing the sp2 domains or doping with graphite nitrogen both cause a redshift in the fluorescence wavelength of CDs in the solid state. Moreover, with the multi‐dimensional and adjustable fluorescence wavelength, the application of AIE CDs in the fields of multi‐anti‐counterfeiting encryption, ink printing, and screen printing is demonstrated. All in all, this work opens up a new way for preparing solid‐state multi‐color CDs using AIE effect, and further proposes an innovative strategy for controlling fluorescence wavelengths.
A Turbo‐Charging System‐Like Contrast Agent for MRI‐Guided STING Pathway‐Activated Cancer Immunotherapy
Authors: Ren Bin , Yan Sihua , Li Zongheng , Huang Ya , Cai Haobin , Yang Jing , Fan Qingdeng , Chen Chunmei , Que Fanchao , Wu Guochao , Huang Lin , Zhou Ruilong , Zhu Jiaoyang , Yan Chenggong , Liu Gang , Shen Zheyu , Ning Shipeng
Published: November 2024

To overcome the problems of Gd‐based contrast agents (GBCAs) (nephrotoxicity and brain deposition) and stimulator of interferon genes (STING) agonists (poor stability, low delivery efficiency, and potential toxicity), in this study, a Turbo‐charging system‐like GBCA is designed and constructed for magnetic resonance imaging (MRI) guided STING pathway‐activated cancer immunotherapy. Poly(acrylic acid) (PAA) is used to coordinate with Gd3+, forming a Gd/PAA macrochelate. Both Gd/PAA macrochelate and SR717 are conjugated to cystamine (CA) to obtain SR717‐CA@Gd/PAA self‐assembled nanoparticles (SAN), which are termed as Turbo S because of its similarity with the Turbo‐charging system of cars. After accumulation in tumors and internalization in tumor cells, the disulfide linkage in Turbo S undergoes a cleavage process catalyzed by glutathione (GSH), leading to the release of Gd/PAA and SR717. The released Gd/PAA gain a high r1 value (17.11 mM−1 s−1 at 7.0 T; 57.81 mM−1 s−1 at 3.0 T), indicating its strong T1 imaging capability. Turbo S with a low dosage of SR717 (8.9 mg kg−1) achieved a higher tumor immunotherapeutic efficacy than free SR717 with a high dosage (30 mg kg−1). The excellent delivery efficiency, high tumor treatment efficacy, and superior biosafety demonstrate that the Turbo S can be used as a promising candidate for tumor immunotherapy.
Beyond Photochromism: Alternative Stimuli to Trigger Diarylethenes Switching
Authors: Ai Qi , Lan Kangjun , Li Lin , Liu Zugang , Hu Xiaoguang
Published: November 2024

Diarylethenes (DAEs) are typical photochemically reversible type (P‐type) photochromic materials with excellent thermal stability and high fatigue resistance and are widely exploited as photo‐switches for various applications in molecular devices, data storage, photoresponsive materials, and bioimaging, etc. In recent years, there is an increasing number of reports using heat, acid, electrochemistry, etc. to drive the isomerization reaction of DAEs. The response to two or more different stimuli enables multi‐functionality within a single DAE molecule, which would facilitate complex logic‐gate operations, multimode data storage, and increased information density. Herein, the recent advances in DAE systems utilizing stimuli “beyond photo” to trigger the isomerization processes from three perspectives: acidochromism, thermochromism, and electrochromism are reviewed. Emphasis is placed on the molecule design strategies and the underlying mechanisms for cyclization and cycloreversion processes addressed by the alternative stimulus. Then the noticeable applications made in multi‐stimuli responsive DAE systems are summarized. Additionally, the challenges and opportunities of DAE switches driven by stimuli “beyond photo” in the future are also discussed.
Assessment of cover crop adoption and impact on weed management in Wisconsin corn‐soybean cropping systems
Authors: Chudzik Guilherme , Nunes Jose J. , Arneson Nicholas J. , Arneson Grace , Conley Shawn P. , Werle Rodrigo
Published: November 2024

The evolution and widespread occurrence of herbicide‐resistant weeds pose a major challenge for farmers and crop consultants across North America, warranting integrated management strategies. The adoption of cover crops offer weed suppression and soil health benefits but adds management complexity. A survey, targeting farmers and crop consultants, was conducted during the spring of 2023 to evaluate current cover crop management practices and perceptions in Wisconsin cropping systems. The survey included 26 questions across five sections: respondent profile, cover crop adoption and experience, cover crop management ahead of soybean [Glycine max (L.) Merr.], cover crop management ahead of corn (Zea mays L.), and general benefits and challenges of cover crop adoption. Farmers and crop consultants represented most respondents, influencing a total of 29,500 and 557,000 ha, respectively. Waterhemp (Amaranthus tuberculatus [Moq.] J.D. Sauer) and giant ragweed (Ambrosia trifida L.) were identified as the most troublesome weeds. Over 90% of respondents use herbicides to terminate their cover crops, and 68% of respondents agree that cover crops improved overall weed control in their farms/clients’ farms to some extent [cereal rye (Secale cereale L.) as main cover crop species]. Additionally, results demonstrate a strong consensus (85%) on cover crops positively influencing water retention, with 98% agreement on their efficacy in reducing soil erosion. Results from this survey can help guide farmers, agronomists, researchers, and policymakers with cover crop adoption, management, policies, incentives, and future research and education needs in Wisconsin and beyond to support the development of more sustainable and efficient weed and crop management strategies.
Quantitative Analysis of the Brachialis and Triceps Brachii Insertion Sites on the Proximal Epiphysis of the Ulna in Modern Hominid Primates and Fossil Hominins
Authors: Ciurana Neus , Casado Aroa , Rodríguez Patrícia , García Marcel , Pastor Francisco , Potau Josep M.
Published: November 2024

In several species of hominid primates with different types of locomotor behavior, we quantitatively studied the insertion sites of the brachialis and triceps brachii on the proximal epiphysis of the ulna. Our main objective was to evaluate the possibility of using the anatomical features of these insertion sites to infer the locomotor behavior of different species of fossil hominins. We measured the area of these muscle insertion sites using 3D bone meshes and obtained the value of each insertion site relative to the total size of the two insertion sites for each of the species studied. We also compared these relative values of the osteological samples with the relative mass of the brachialis and triceps brachii, which we obtained by dissecting these muscles in the same primate species. The relative values for the brachialis insertion were highest in orangutans, followed by bonobos, chimpanzees, gorillas, and humans. Fossil Australopithecus and Paranthropus had values similar to those of bonobos, while fossil Homo had values similar to those of Homo sapiens. The observed similarity in ulnar attachment sites between Australopithecus and Paranthropus and extant bonobos suggest that these hominins used arboreal locomotion to complement their bipedalism. These adaptations to arboreal locomotion were not observed in Homo.
Male Infanticide in the Northern Purple‐Faced Langur (Semnopithecus vetulus Philbricki) in the Kaludiyapukuna Forest Reserve, Sri Lanka
Authors: Salmi Roberta , Lu Amy , Hofner Alexandra N. , Madushan Charith , Thisaru Dilan , Mallott Elizabeth K. , Vandercone Rajnish
Published: November 2024

Infanticide, the killing of conspecific infants, has been observed in many species, including rodents, carnivores, and notably, primates. Although several adaptive and non‐adaptive hypotheses have been proposed to explain this phenomenon, most cases to date appear consistent with the sexual selection hypothesis, particularly in primates. According to this hypothesis, males increase their reproductive success by eliminating unrelated unweaned infants, causing females to resume cycling earlier and allowing infanticidal males to mate and sire offspring sooner during their tenure. Here, we document the first confirmed cases of male infanticide in the Northern purple‐faced langur, an endangered Sri Lankan colobine living in polygynous groups where outside males challenge resident males for reproductive access, resulting in a “takeover.” Following one male takeover, we documented infanticidal attacks on all three infants present, resulting in the wounding and killing of two and the disappearance of the third, all within the first 2 months of the male's tenure. We also describe: (1) changes in group composition following the male replacement, (2) the age and sex of the victims and perpetrator/s; (3) the effect of infant loss on female interbirth interval; (4) infant defense; and (5) mating access to the victim's mothers after the infanticide. We conclude that despite anthropogenic disturbance at some study sites, infanticide within this species appears to align with the sexual selection hypothesis. Nonetheless, genetic analyses on infants killed and born after the takeover are needed to provide conclusive evidence.
Dicyclopenta[4,3,2,1‐cde:4′,3′,2′,1′‐pqr]‐peri‐tetracene: Synthesis and an Example of Annulene‐within‐an‐Annulene Aromaticity in Different Redox States
Authors: Jiang Qing , Han Yi , Hou Xudong , Wu Shaofei , Xu Tingting , Orozco‐Ic Mesías , Merino Gabriel , Chi Chunyan
Published: November 2024

We report a robust strategy for tuning the electronic structure and chemical stability of π‐conjugated polycyclic hydrocarbons (PHs). By fusing two cyclopentadienyl rings in the peri‐tetracene bay regions, we introduce antiaromatic character into the π‐system, leading to unique photophysical and electronic properties. A stable mesityl‐substituted dicyclopenta‐peri‐tetracene derivative was synthesized through stepwise formylation/intramolecular cyclization at the bay regions of the dihydro peri‐tetracene precursor, followed by oxidative dehydrogenation. This compound features an open‐shell singlet diradical ground state, global antiaromaticity, exceptional stability under ambient conditions, and amphoteric redox behavior with a small energy gap. Its dication also possesses an open‐shell singlet ground state, and its structure was identified by X‐ray crystallographic analysis, revealing a unique [14]annulene‐within‐[22]annulene global aromatic structure. In contrast, the dianion exhibits a closed‐shell singlet ground state. This work provides valuable insights for designing and synthesizing novel open‐shell PHs with tunable electronic structures and remarkable stability.
Molecular Chain Rearrangement of Natural Cellulose‐Based Artificial Interphase for Ultra‐Stable Zn Metal Anodes
Authors: Wang Jizhen , Jiao Long , Yi Chao , Bai Hongyuan , Liu Qiaoyun , Fu Yusen , Liu Jiajia , Wang Chuang , Lei Yechen , Zhang Tian , Wen Jiaqi , Yang Leixin , Shu Dengkun , Yang Shuo , Li Chenyang , Li Huan , Zhang Wenjun , Cheng Bowen
Published: November 2024

The unstable electrolyte‐anode interface, plagued by parasitic side reactions and uncontrollable dendrite growth, severely hampers the practical implementation of aqueous zinc‐ion batteries. To address these challenges, we developed a regenerated cellulose‐based artificial interphase with synergistically optimized structure and surface chemistry on the Zn anode (RC@Zn), using a facile molecular chain rearrangement strategy. This RC interphase features a drastically increased amorphous region and more exposed active hydroxyl groups, facilitating rapid Zn2+ diffusion and homogeneous Zn2+ interface distribution, thereby enabling dendrite‐free Zn deposition. Additionally, the compact texture and abundant negatively charged surface of the RC interphase effectively shield water molecules and harmful anions, completely preventing H2 evolution and Zn corrosion. The superior mechanical strength and adhesion of the RC interphase also accommodate the substantial volume changes of Zn anodes even under deep cycling conditions. Consequently, the RC@Zn electrode demonstrates an outstanding cycling lifespan of over 8000 hours at a high current density of 10 mA cm−2. Significantly, the electrode maintains stable cycling even at a 90 % depth of discharge and ensures stable operation of full cells with a low negative/positive capacity ratio of 1.6. This study provides new solution to construct highly stable and deep cycling Zn metal anodes through interface engineering.
Thieno[3,2‐b]pyridine: Attractive scaffold for highly selective inhibitors of underexplored protein kinases with variable binding mode
Authors: Moyano Paula Martín , Kubina Tadeáš , Paruch Štěpán Owen , Jarošková Aneta , Novotný Jan , Skočková Veronika , Ovesná Petra , Suchánková Tereza , Prokofeva Polina , Kuster Bernhard , Šmída Michal , Chaikuad Apirat , Krämer Andreas , Knapp Stefan , Souček Karel , Paruch Kamil
Published: November 2024

Protein kinases are key regulators of numerous biological processes and aberrant kinase activity can cause various diseases, particularly cancer. Herein, we report the identification of new series of highly selective kinase inhibitors based on the thieno[3,2‐b]pyridine scaffold. The weak interaction of the thieno[3,2‐b]pyridine core with the kinase hinge region allows for profoundly different binding modes all of which maintain high kinome‐wide selectivity, as illustrated by the isomers MU1464 and MU1668. Thus, this core structure provides a template of ATP‐competitive but not ATP‐mimetic inhibitors that are anchored at the kinase back pocket. Mapping the chemical space around the central thieno[3,2‐b]pyridine pharmacophore afforded highly selective inhibitors of the kinase Haspin, exemplified by the compound MU1920 that fulfils criteria for a quality chemical probe and is suitable for use in in vivo applications. However, despite the role of Haspin in mitosis, the inhibition of Haspin alone was not sufficient to elicit cytotoxic effect in cancer cells. The thieno[3,2‐b]pyridine scaffold can be used in a broader context, as a basis of inhibitors targeting other underexplored protein kinases, such as CDKLs.