bluuebunny/crossref_metadata_2025 huggingface dataset:
Tail risk market spillovers of oil to agricultural commodities: A time-frequency quantile approach
Authors: Olayinka Hammed Abiola , Khan Naveed , Adesina Oluwaseun A. , Yaya OlaOluwa S.
Published: January 2025

The interplay between commodities and oil prices provides a trade-off for investors and consumers. However, the increasing interconnectedness between these two series helps investors to design efficient investment strategies. Therefore, in this paper, the risk spillovers from oil market prices to that of agricultural commodities, namely, corn, wheat, soybeans, sugar, cotton, cocoa, coffee, lean hogs, and live cattle for the period spanning from May 1987 to December 2023 was investigated. For the analysis, we employ a quantile frequency connectedness approach, our findings reveal that under all market conditions (normal, bearish, and bullish) corn, wheat, and soybean are the return spillovers’ net transmitters, but sugar is a consistent net shocks receiver across all frequencies. Furthermore, agricultural commodities receive oil shocks from WTI during normal market conditions. At lower market conditions, the connectedness between commodities and oil is weaker than that of extreme market conditions (higher quantiles). Moreover, the network plots show that short-run connectedness dominates the long-run connectedness at price returns extremes. Similarly, our finding reports significant implications for policymakers, portfolio managers, and investors to diversify their investments in different market conditions.
JEL codes: C22 F21 G11 G13 G32
Bioinformatics Identification of Lactate-Associated Genes in Hepatocellular Carcinoma: G6PD’s Role in Immune Modulation
Authors: Qu Hao-ran , Wang Chao-qun , Sun Su-juan , Zhang Wen-wen , Du Xuan-shuang , Shuozhuo Yi-ao , Wang Xi-cheng , Pan Qin , Luo Feng-ling , Wu Hong-yan , Zhang Xiao-lian , Liu Min
Published: January 2025

Background
Hepatocellular carcinoma (HCC) is a major global health issue, with poor prognosis often associated with dysregulated metabolic pathways, especially lactate metabolism. This study explored the prognostic significance of lactate-associated genes in HCC and their potential as therapeutic targets.
Methods
We analyzed RNA-seq and clinical data from 374 patients with HCC from The Cancer Genome Atlas (TCGA) database. Using Cox regression, LASSO analysis, and Kaplan-Meier survival curves, we identified key lactate-associated genes associated with patient outcomes. Functional validations, including Western blot, flow cytometry, and molecular docking studies, were performed to confirm the biological impact of these genes.
Results
G6PD, IK, and CALML5 were identified as significant prognostic markers for HCC. A prognostic model was developed that effectively stratified patients into risk groups, which correlated with survival. G6PD’s role in immune modulation and its potential as a drug target were validated through biochemical assays and computational analyses. Functional assays in HepG2 cells confirmed that alterations in G6PD expression affect T cell activity, with knockdown enhancing IFN-γ production and overexpression inhibiting it, demonstrating G6PD’s role in immune evasion.
Conclusions
This study establishes lactate metabolism genes, particularly G6PD, as key prognostic markers in HCC. The validation of G6PD’s immunomodulatory effects further supports its potential as a therapeutic target for strategies aimed at enhancing immune surveillance and treatment outcomes in HCC.
Identification and Quantification of Primary Pollutants Impacting Aquaculture in Mine Surface Plant Areas
Authors: Kashale Chimanga , Jere Ezekiel Bob , Chembe Christopher
Published: January 2025

The aim of this study was to investigate and identify the primary pollutants impacting aquaculture in mine surface plant areas of Kalumbila District. Water samples were collected from four sites near mining operations to analyze key pollutants, including iron, copper, and cobalt, along with water quality parameters such as pH, dissolved oxygen (DO), temperature, and conductivity. Results revealed elevated cobalt levels (up to 60 mg/L at Site 1, far exceeding the recommended 0.01 mg/L), significant copper contamination, and slightly acidic conditions, particularly near the contamination source. Dissolved oxygen levels were lowest at Site 1 (4.5 ± 0.6 mg/L), indicating potential stress on aquatic life. The study demonstrated that proximity to mining activities exacerbates pollution levels, with pollutant concentrations decreasing at sites further away due to natural attenuation. The toxic effects of heavy metals, low DO, and high conductivity on aquatic ecosystems were assessed, highlighting severe risks such as gill damage, bioaccumulation, and osmotic stress, particularly at Site 1. These findings align with related studies on the ecological impacts of mining and emphasize the urgent need for targeted mitigation strategies. Recommendations include implementing advanced pollution control technologies, enhancing monitoring systems, and promoting sustainable mining practices. The study underscores the importance of balancing industrial activities with environmental preservation to safeguard aquatic ecosystems and local livelihoods.
Inhibition of TERT suppressed proliferation and induced apoptosis in chronic myeloid leukemia cells
Authors: Liu Wen , Deng Fang , Wang Teng
Published: January 2025

Purpose
The targeting of telomerase in cancer therapy elicits significant attention due to recent findings indicating a correlation between high telomerase activity and adverse cancer outcomes, as well as disease resistance. The precise role of telomerase and its catalytic subunit, human telomerase reverse transcriptase (hTERT), in chronic myeloid leukemia (CML) has not been thoroughly elucidated. However, telomerase activity is recognized as a mechanism underlying resistance to imatinib (IM), a tyrosine kinase inhibitor. The loss of telomerase activity in CML has also been associated with acquiring infinite proliferative potential, which is closely linked to maintenance through telomerase reactivation.
Methods
K562 cells, along with their IM-resistant derivatives (K562R), were subjected to si-RNA targeting hTERT or a combination treatment involving IM and the hTERT inhibitor BIBR1532. To evaluate the role of hTERT in drug resistance, cell viability following exposure to si-hTERT, IM, and the combination of IM and BIBR1532 was evaluated using the Cell Counting Kit-8 (CCK-8) assay and colony-formation assays. The percentage of apoptosis was quantified using the Annexin V assay. Additionally, the transcriptional and protein expression levels of p73, p21, FOXO3a, c-Myc, hTERT, and other apoptosis-related target genes were analyzed through quantitative polymerase chain reaction (qPCR) and Western blotting (WB).
Results
In K562R and K562 cell lines, telomerase activity was significantly reduced following the pharmacological inhibition of telomerase using the inhibitor BIBR1532, as well as through the knockdown of hTERT. Flow cytometry analysis revealed that the knockdown of hTERT induced apoptosis in chronic myeloid leukemia (CML) cells and results in cell-cycle arrest at the G2 phase. Furthermore, the inhibition of hTERT was found to suppress the transcriptional activity of c-Myc while concurrently reactivating the transcription factors p73, p21, and Foxo3a. The combination of BIBR1532 with imatinib exhibited a synergistic anticancer effect on CML cells.
Conclusions
Overall, the combination of BIBR1532 is a novel therapeutic strategy for CML that may soon be clinically accessible.
Long-term survival outcome of portal vein embolization in patients with perihilar cholangiocarcinoma
Authors: Lee Min Woo , Paik Woo Hyun , Huh Gunn , Lee Dong Ho , Bae Jae Seok , Kwon Woo Il , Jang Jin Young , Cho In Rae , Ryu Ji Kon , Lee Sang Hyub
Published: January 2025

Background
Portal vein embolization (PVE) is often recommended to avoid postoperative liver failure and subsequent mortality after surgical resection of perihilar cholangiocarcinoma (CCA). However, evidence of its effect on surgical outcomes and long-term survival is limited.
Methods
We retrospectively reviewed the data of 137 patients diagnosed with Bismuth type III–IV perihilar CCA between April 2011 and August 2021. Among 137 patients, 88 were included in the analyses and divided into three groups: resection without PVE (A); resection after PVE (B); and no resection after PVE (C). We analyzed the outcomes using inverse probability treatment weighting (IPTW). Factors associated with overall survival were analyzed using Cox regression analysis stratified by surgical resection.
Results
There was no significant difference in median overall survival (OS) and recurrence-free survival (RFS) between groups A and B (mOS 19.6 vs. 26.6 months; P = 0.382; mRFS 11.9 vs. 18.1 months, P = 0.099). However, a significant difference was found in median OS between groups B and C (26.6 vs 10.5 months; P = 0.004). In the stratified Cox regression analysis with IPTW, age (adjusted hazard ratio [aHR] 1.364ㅡ10.97), CA19-9 level (aHR 1.181ㅡ4.147), and percentage of future liver remnant after PVE (post-PVE %FLR; aHR 0.180ㅡ0.815) were associated with OS.
Conclusions
There was no difference in OS and RFS based on whether PVE was performed before surgical resection. Post PVE %FLR was associated with OS irrespective of subsequent surgical resection.
Morphological segmentation with tiling light sheet microscopy to quantitatively analyze the three-dimensional structures of spinal motoneurons
Authors: Hu Huijie , Wang Dongyue , Chen Yanlu , Gao Liang
Published: January 2025

Spinal motoneurons control muscle fibers contraction and drive all motor behaviors in vertebrates. Although spinal motoneurons share the fundamental role of innervating muscle fibers, they exhibit remarkable diversity that reflects their specific identities. Defining the morphological changes during postnatal development is critical for elucidating this diversity. However, our understanding of the three-dimensional (3D) morphology of spinal motoneurons at these stages remains limited, largely due to the lack of high-throughput imaging tools. Using tiling light sheet microscopy combined with tissue clearing methods, we imaged motoneurons of the lateral and median motor column in the cervical and lumbar cord during postnatal development. By analyzing their soma size, we found that motoneurons innervating the upper limbs differentiate into two subpopulations with distinct soma size by postnatal day 14 (P14), while differentiation of motoneurons innervating the lower limbs is delayed. Furthermore, coupling adenovirus labeling with 3D volumetric reconstruction, we traced and measured the number and lengths of dendrites of flexor and extensor motoneurons in the lumbar cord, finding that the number of dendrites initially increases and subsequently declines as dendritic order rises. Together, these findings provide a quantitative analysis of the 3D morphological changes underlying spinal motoneuron diversity.
Metode Gamifikasi untuk Pembelajaran Menulis Cerpen Siswa Kelas XI SMK Islam Darussalam
Authors: Ramadhani Abd Wafir , Wachidah Liana Rochmatul
Published: January 2025

This article analyzes the application of gamification methods that are used as an effort to improve the short story writing skills of class XI students of SMK Islam Darussalam. Gamification is a learning method that involves game elements such as leaderboards, points, challenges, and prizes in learning, which are proven to be able to create interesting and interactive learning. This study uses a qualitative method with a case study approach. This approach is used because it allows researchers to gain a deep understanding of the phenomenon being studied in a real context. This study shows that the gamification method can improve students' writing skills, because its application can create active and enjoyable learning. The thing that must be considered in implementing this method is the right strategy, because with the right strategy gamification has the potential to create dynamic and student-centered learning, thus helping students improve their skills, especially short story writing skills.
Strategies for the Regional Development of Jeollanam-do through Marine Specialization: Developing Human Capital and International Student Policies
Authors: Kim Jae-Eun
Published: January 2025

This proposes strategies for the regional development of Jeollanam-do through marine specialization. Jeollanam-do boasts an abundance of islands and marine resources, with agriculture and fisheries being the primary industries. However, rapid population decline and urbanization threaten the sustainability of its development. By analyzing the 5th National Comprehensive Territorial Plan and Jeollanam-do's 4th Comprehensive Plan, this research derives sustainable development strategies to leverage the region's unique resources. Emphasizing the pivotal role of local universities such as Mokpo National University, it discusses how revitalization of island- and marine-centered industries and tourism can be achieved through regional talent cultivation and development. It further highlights the necessity of fostering talent, enhancing research and development capabilities, attracting domestic and international students, expanding cooperation between local universities and industries, and utilizing historical and cultural resources. In conclusion, it is anticipated that marine specialization strategies reflecting Jeollanam-do's unique characteristics will contribute to balanced regional development and sustainability.
Diferenciação Social
Authors: Ferrari Carlos , Mocarzel Rafael , Graça Amândio , Santos Roberto
Published: January 2025

O artigo tenciona analisar quais as teias de interdependência que determinam o lugar da educação física numa escola TEIP. A investigação caracteriza-se por uma pesquisa qualitativa, de cunho sociocultural. Nesse ajustamento, é possível assegurar, com base na leitura da paisagem social, que o aluno em voga nutre um sentimento singular quanto à educação física. Nessa ordenação, entretanto, constata-se que o papel da escola, do (ser) professor de educação física, em particular, é acometido pelo arbítrio da estrutura dominante, resultando no déficit qualitativo no que se refere à formação integral do alunado em destaque. Contudo, é preciso sublinhar que, no caso da dita unidade escolar, há indicadores que supostamente teceriam um equilíbrio de poder mais ou menos instável, quanto à ‘legitimação’ da educação física.
Vulnerabilidade de Mães Solo: Desromantizando a Ideia de “Mulheres Guerreiras”
Authors: Garcia Laurindo Pereira Jarmara , Atanazio Xavier Larissa , Miranda de Amorim Resende Camila
Published: January 2025

O presente estudo tem como finalidade conhecer a vivência e a história de algumas mães solo do município de Volta Redonda e adjacências e desconstruir a idealização de que mães solo são mulheres fortes, guerreiras e batalhadoras. Para tal buscar entender o significado e sentido do termo “mãe solo”; investigar a realidade de mães solo e suas experiências de vida; e conhecer a vulnerabilidade vivenciada por mulheres mães solo. A metodologia utilizada no presente artigo se classifica, quanto aos fins, em uma pesquisa qualitativa, de campo e bibliográfica, de caráter exploratório e descritiva, que utilizou como instrumento entrevistas semiestruturadas que permitiram as entrevistadas discorrerem livremente sobre o tema da pesquisa. Para compreender a vivência e a história dessas mães, foram realizadas entrevistas com quinze mulheres mães solo na região sul fluminense. Foi possível identificar cinco dimensões de análise que se revelaram primordiais para o objetivo da pesquisa, como: “A aliança: poder e respeito”, “A naturalização do abandono paterno”, “O peso da maternidade solitária”, “Não é amor, é abuso” e “Mães que caminham sozinhas: a romantização da sobrecarga”. Na primeira dimensão, abordou-se o preconceito vivenciado por essas mulheres, onde foi destacado que a aliança tem um peso significativo no meio social. Referente a segunda dimensão, foi exposto a naturalização do abandono paterno perante a sociedade. Na terceira dimensão, foi tratado o sentimento de culpa e arrependimento existentes na vida das mães solo em consequência do abandono paterno. A quarta dimensão trata do relacionamento abusivo que 13 das 14 mulheres entrevistadas relatam terem vivido com o pai de seus filhos. A quinta e última dimensão traz a reflexão da sobrecarga na maternidade solo, bem como suas fragilidades perante essa jornada solitária. Observou-se que expressões como “mulheres fortes e guerreiras” direcionadas as mulheres mães solo são construídas pelo meio social que romantiza o peso da maternidade solo, bem como naturaliza o abandono paterno. É essencial a real compreensão dessas vivências, sem rótulos, uma vez que são experiências únicas e delicadas de serem vividas.
Abordagem da Teoria das Representações Sociais em Relação à Interação entre Família e Escola: Avaliação de Teses e Dissertações Apresentadas em Programas de Pós-Graduação no Brasil
Authors: Bicalho Adriana Vicente , Da Silva Triani Felipe
Published: January 2025

O propósito deste texto foi realizar um levantamento e análise de teses e dissertações apresentadas entre 2011 e 2021 em programas de pós-graduação no Brasil, abordando as representações sociais e a interação entre família e escola no contexto educacional. A pesquisa foi conduzida na Plataforma Digital de Catálogo de Teses e Dissertações da Capes, utilizando as palavras-chave "representações sociais", "família" e "escola". Ao realizar essa análise buscou-se obter uma visão panorâmica das pesquisas realizadas ao longo de uma década em relação à temática e identificar padrões, lacunas e tendências no ambiente escolar na integração entre família e escola. Os resultados indicam uma limitada adoção da Teoria das Representações Sociais pelos estudantes de pós-graduação brasileiros que exploram temas relacionados à família e à escola. As pesquisas destacam que a família e o aluno são considerados os principais responsáveis pelo fracasso escolar e pela falta de sucesso acadêmico, enquanto a desigualdade social é apontada como um fator que contribui para a falta de motivação e deficiência na aprendizagem. No entanto, alguns estudos retratam a escola como um ambiente de formação que promove o progresso e oferece oportunidades profissionais mais promissoras.
Desenvolvimento e Validação de Produto Educacional sobre Primeiros Socorros voltados a Recém-Nascidos:Estudo Metodológico
Authors: Zuccon e Silva Fernando , Nunes Guedes de Oliveira Rebeca
Published: January 2025

RESUMO: A morte de recém-nascidos ocasionada por engasgamento, aspiração de corpo estranho e morte súbita ainda representa elevada magnitude em diversos cenários. Em junho de 2022, a Secretaria Municipal da Casa Civil de São Paulo publicou a Lei no 17.811, que dispõe sobre a obrigatoriedade de os hospitais e maternidades capacitarem os pais ou responsáveis de recém-nascidos para realizarem atendimento de primeiros socorros para os casos de engasgamento, aspiração de corpo estranho e prevenção de morte súbita. O estudo aborda o processo de desenvolvimento de estratégia educativa voltada à prevenção deste problema em um serviço público de saúde. O objetivo foi  elaborar e validar um vídeo educativo para os pais ou responsáveis de recém-nascidas sobre como realizar manobras de primeiros socorros para os casos de engasgamento, aspiração de corpo estranho e prevenção de morte súbita. Trata-se de um estudo metodológico que foi constituído pelas fases de concepção, desenvolvimento e validação, pelo público-alvo, de um produto educacional. Os conteúdos do vídeo foram definidos a partir de levantamento bibliográfico, realizado nas bases de dados PubMed; LILACS; Google scholar, respectivamente, usando os descritores “Morte Súbita do Lactente”; “Engasgo”; “aspiração de corpo estranho”; e “primeiros socorros”. O produto educacional foi desenvolvido no formato de vídeo educativo. Para a validação do vídeo junto ao público-alvo, foi aplicado questionário após a exposição do vídeo a puérperas e aos respectivos responsáveis legais dos recém-nascidos na Maternidade do Conjunto Hospitalar do Mandaqui. Após a apresentação do vídeo e aplicação do questionário junto ao público-alvo, foi aplicado o Índice de Validação de Conteúdo, avaliado quanto ao, objetivos, organização, estilo do vídeo, aparência e motivação, seguindo, de forma adaptada, o questionário publicado por Dantas et al. (2022). Foi obtida a validação do produto com um IVC total de 0,99. Como produto de pesquisa foi desenvolvido foi um vídeo educativo validado, vislumbrando a sua implementação no cenário do estudo, com possibilidade de ampliação a partir de ampla divulgação do material para toda a rede de saúde.
 
Palavras-chave: atenção à saúde; garantia da qualidade dos cuidados de saúde; morte súbita do lactente; engasgo; primeiros socorros.
Nível de Atividade Física e o Impacto na Saúde dos Alunos de Medicina na Pandemia por Covid-19
Authors: Dias Carrijo da Costa Eduarda , Dias Carrijo da Costa Leonardo , Tavares Lima Trajano Eduardo , Alexsandra da Silva Neto Trajano Larissa , Zubcich Caiado de Castro Pedro Henrique , Alves Fontes Iberico
Published: January 2025

A prática de atividade física (AF) influencia na qualidade de vida do indivíduo de forma direta, uma vez que a prática regular leva a melhora de parâmetros cardiovasculares e prevenção de doenças crônicas. Este estudo buscou identificar a prevalência de AF dos estudantes de medicina durante a pandemia por COVID-19. Os procedimentos metodológicos adotados consistem em um estudo observacional-transversal que teve como amostra, 202 estudantes do curso de medicina da Universidade de Vassouras – Rio de Janeiro. A coleta de dados foi realizada através de um questionário online. Ao analisar os dados, 30,7% dos estudantes possuem baixos níveis de AF. Concluímos que o isolamento social provocou uma série de impactos na saúde da população estudada, com destaque para a diminuição na prática de AF e piora de hábitos alimentares. Faz-se necessário o incentivo à prática de AF regularmente, inclusive em tempos de pandemia, como medida para melhor enfrentar os desafios do isolamento social à saúde.
Sociedade de Risco e Modernidade Reflexiva: Desafios e Oportunidades na Perspectiva de Ulrich Beck
Authors: Dutra Gresele Wanderson , Cunha Messias Hayla , Signor Altevir
Published: January 2025

A modernidade gerou uma série de desafios e oportunidades que exigem uma nova compreensão dos problemas sociais. Em 1986, Ulrich Beck publicou "Sociedade de Risco", oferecendo uma nova perspectiva sobre esses desafios. Este trabalho visa compreender os princípios fundamentais da obra Sociedade de Risco: rumo a uma outra modernidade de autoria de Ulrich Beck, buscando destacar as ideias essenciais que fornecem perspectivas e insights para a compreensão social. Beck aborda os riscos modernos como intrínsecos ao próprio progresso e destaca uma transformação nos fundamentos da modernidade industrial. Observa que os eixos da família e do emprego, bem como a crença na ciência e no progresso, estão começando a cambalear. Esta mudança resulta no surgimento de novas oportunidades e riscos, delineando os contornos da sociedade de risco. A obra de Beck, portanto, é crucial para entender como a modernidade reflexiva redefine nossa abordagem aos riscos e às incertezas no mundo contemporâneo.
Modelo de Ensino One Minute Preceptor nos Cenários de Urgência e Emergência
Authors: Souza Maria Cristina Almeida de , Vilagra Lahis Werneck
Published: January 2025

As Diretrizes Curriculares Nacionais para o Curso de Medicina, em vigor desde 2014, definem o internato como período obrigatório nos dois últimos anos de formação, buscando aproximar os estudantes da prática médica e do "saber tratar", onde devem passar por vários cenários de prática, entre eles a urgência e emergência (UE). Essencial nesse cenário é o preceptor, profissional que, ao mesmo tempo que desenvolve atividades assistenciais, acompanha e orienta o estudante. Este trabalho tem como objetivo conhecer o perfil e as necessidades pedagógicas dos preceptores atuantes nos cenários de UE do internato médico da Univassouras (Vassouras-RJ), bem como propor capacitação utilizando o modelo OMP. Realizou-se uma pesquisa de campo com preceptores do HUV. Adotou-se uma abordagem através coleta de dados por questionários e análise das reflexões dos preceptores. A aprovação ética foi obtida junto ao Comitê de Ética em Pesquisa da Universidade de Vassouras. A participação foi de 78% dos preceptores. A análise qualitativa dos discursos é condizente com a literatura e revela a necessidade de formação pedagógica e aprimoramento na integração entre papéis de ensino e atividade clínica, bem como a factibilidade do uso do OMP nesse cenário. Concluiu-se que o perfil de participantes no estudo é de preceptores que valorizam o treinamento pedagógico, mas não têm conhecimento sobre o OMP.
Núcleo Central das Representações Sociais na Formação Inicial de Estudantes de Educação Física
Authors: Fagundes D'Albuquerque Pereira Fábio Cesar , Felício Brito Carlos Alexandre
Published: January 2025

Este estudo explora as representações sociais de estudantes de Educação Física, focando nos cursos de Bacharelado e Licenciatura, durante os primeiros semestres de formação. Identificar o núcleo central das representações sociais sobre Educação Física entre os estudantes, analisando como essas percepções são construídas e influenciadas ao longo da formação. A pesquisa adotou uma abordagem qualitativa, ancorada na Teoria do Núcleo Central das Representações Sociais, utilizando a Técnica de Associação Livre de Palavras para coleta de dados. A análise foi realizada com o software IRaMuTeQ. Os dados revelam uma predominância de alunos recém-ingressos com maior interesse pelo Bacharelado. As evocações indicam que as representações sociais são influenciadas pelo contexto educacional e pela experiência prévia dos estudantes. As representações sociais dos discentes refletem tanto as influências culturais e históricas quanto suas experiências individuais e expectativas sobre a Educação Física.
Relato de Experiência sobre o Kung-Fu como Disciplina do Ensino Superior
Authors: Mocarzel Rafael Carvalho da Silva
Published: January 2025

O objetivo deste trabalho foi de tecer um relato de experiência sobre a criação e inclusão de uma disciplina curricular de nível superior no Brasil. Mais especificamente, tal criação e inclusão se deu nos cursos de graduação (Licenciatura e Bacharelado) em Educação Física sobre a arte marcial chinesa conhecida como Kung-Fu. A ação ocorreu em uma renomada universidade federal do país. Para realização dessa tarefa, o presente trabalho bebeu de fontes da etnometodologia, detalhando a idealização, estruturação e execução do processo de implementação da referida disciplina. O processo levou quatro semestres (um para estruturação e três em execução). Após a crescente da procura dos discentes pela disciplina e pela qualidade dos trabalhos finais, acredita-se que o resultado final foi de um projeto bem-sucedido.
O Herói Mitológico em “O Mito do Nascimento do Herói” de Otto Rank
Authors: Rosa Alves Ana Tércia , Freitas Pinto Weiny César
Published: January 2025

Este artigo investiga a análise e interpretação do mito do herói por Otto Rank em seu livro “O mito do nascimento do herói” (1909/1922), no contexto da aplicação da Psicanálise à Mitologia. A investigação foca na contribuição de Rank para a compreensão simbólica dos mitos sob a perspectiva psicanalítica. Uma vez que Freud reconheceu a contribuição das ciências humanas para a Psicanálise, o estudo justifica-se pela necessidade de compreender a interseção entre Psicanálise e Mitologia. O objetivo geral é analisar a abordagem de Rank em relação ao mito do herói, destacando sua metodologia e suas principais conclusões. Foram utilizadas duas traduções da obra de Rank, uma em inglês, baseada na edição de 1909, e outra em português, da edição ampliada de 1922, para comparar e explorar as contribuições de Rank ao longo de suas publicações.
Mucosal Melanoma: An Overview of Recent Therapies
Authors: Griffin Zachary , Mattei Jane
Published: January 2025

Mucosal Melanoma (MM) is an aggressive disease that is distinct from cutaneous melanoma risk in
risk factors, prognosis, and treatment. Surgical treatment is currently the treatment of choice for localized disease;
however, the recurrence rate is common. For advanced or metastatic disease, immunotherapy with PD-1
inhibitors and anti-CTLA is generally first-line treatment, however the overall responses to immunotherapy in
MM are often lower and less robust when compared to that observed in cutaneous melanoma. Adoptive-TIL
therapy have shown great promise. Other advances, particularly through the exploration of novel and combination
therapies is a step forward and a hope to improve outcomes in patients with mucosal melanoma. In this review,
we summarize current treatment options for MM, and we updated future clinical trials available for this
population of patients.
Phage Therapy: A Promising Treatment Strategy against Infections Caused by
Multidrug-resistant Klebsiella pneumoniae
Authors: Zhang Jinghan , Chen Siyue , Sun Xiaoxiao , Chen Sheng , Cheng Qipeng
Published: January 2025

Klebsiella pneumoniae (KP) is a common and highly pathogenic pathogen, which often causes several
serious infections in humans. The rampant and inappropriate use of broad-spectrum antibiotics has fueled
a worrisome surge in Multidrug Resistance (MDR) among the strains of K. pneumoniae, which has significantly
boosted the risk and complexity of nosocomial infection transmission in clinical settings. Consequently, this
situation presents a substantial challenge to the efficacy of anti-infective treatments, making the development
of new and innovative therapeutic approaches important. Bacteriophages (phages) are viruses that can infect
and kill bacteria. They and their derived products are now being considered as promising alternatives or adjuncts
to antimicrobial therapies for treating bacterial infections in humans, which exhibit a remarkable safety
profile and precise host specificity. Numerous studies have also unequivocally demonstrated the remarkable
potential of phages in effectively combating MDR K. pneumoniae infections both in vitro and in vivo. These
studies have explored various approaches to K. pneumoniae phages, such as phage cocktails, phage-derived enzymes,
and the synergistic utilization of phages and antibiotics. Therefore, phage therapy is old but not obsolete,
particularly in light of the escalating problem of antimicrobial-resistant K. pneumoniae infections. Here,
we have presented a comprehensive summary of the current knowledge on phage therapy for K. pneumoniae
infections, including phage distribution, in vitro characterization of phages, in vivo investigations, and cases of
clinical study. This review highlights the rapid advancements in phage therapy for K. pneumoniae, offering a
promising avenue for combating this global public health threat.
Virtual Screening Identifies Inhibitors of SARS-CoV-2 Main Protease through
Pharmacophore and Similarity Approaches
Authors: Khanfar Mohammad A. , Saleh Mohammad
Published: January 2025

Introduction:

The emergence of SARS-CoV-2 and the COVID-19 pandemic highlighted the urgent
need for novel antiviral therapies. The main protease (Mpro) of SARS-CoV-2 is a key enzyme in viral replication and a promising therapeutic target.

Methods:

This study employed virtual screening approaches to identify potential Mpro inhibitors, leveraging
both structure- and ligand-based methods.

Results:

Two optimum pharmacophore models were built from hundreds of crystallographic structures of Mpro
,
validated through ROC curve analysis and Dynophores dynamic simulations. These models captured ≈ 60K
hits from six diverse compound libraries made of more than 3 million compounds. Additionally, a ligandbased similarity search using ROCS software identified 1024 potential hits based on shape and atom-based
comparisons with co-crystallized ligands. Subsequent molecular docking and filtering based on physicochemical properties and structural diversity yielded 16 and 6 hits from structure- and ligand-based screening, respectively. Molecular dynamics simulations were conducted on the top-scoring hits to assess their binding stability
within the Mpro active site. SCR00943 demonstrated stable binding, interacting favorably with key residues, including the catalytic dyad, resulting in a binding affinity of -61.2 kcal/mol

Conclusion:

This virtual screening campaign identified promising Mpro inhibitors, showcasing the potential of
computational approaches to accelerate drug discovery efforts against COVID-19.
Unveiling the Interplay between Dopamine-like Molecules and Β-Amyloid Peptide: A Combined Molecular Dynamic and DFT Approach
Authors: Zand Mohammad Erfan , Bozorgmehr Mohammad Reza , Heravi Mohammad Momen , Beyramabadi S. Ali
Published: January 2025

Aims:

This study aims explore the impact of catechol, dopamine, and L-DOPA on the
stability and toxicity of β-amyloid peptides, which play a key role in the neurodegenerative process
of Alzheimer's disease, to assess their potential as therapeutic agents.

Background:

Alzheimer's disease is marked by the aggregation of β-amyloid peptides, which
contribute to neurodegeneration. Exploring how various compounds interact with β-amyloid
peptides can offer valuable insights into potential therapeutic strategies.

Objective:

The objective of this research is to explore the interaction mechanisms of catechol,
dopamine, and L-DOPA with β-amyloid peptides and assess their impact on peptide stability and
aggregation.

Method:

This study employs molecular dynamics simulations combined with density functional
theory to investigate the interactions between β-amyloid and the three compounds. It evaluates
changes in peptide stability and salt bridge lengths and performs electronic structure analyses using
the Electron Localization Function (ELF) and Harmonic Oscillator Model of Aromaticity
(HOMA).

Results:

The findings reveal that β-amyloid stability decreases significantly when interacting
with dopamine and L-DOPA compared to catechol. All three compounds inhibit β-amyloid, with
dopamine and L-DOPA showing stronger effects. Catechol primarily interacts through hydrophobic
interactions, while dopamine and L-DOPA also form hydrogen bonds with β-amyloid.
Electronic structure analysis shows catechol has higher electron localization and anti-aromatic
character, affecting its interactions differently than dopamine and L-DOPA. A decrease in the
HOMO-LUMO gap from catechol to L-DOPA to dopamine indicates increasing reactivity towards
β-amyloid.

Conclusion:

Dopamine and L-DOPA more effectively disrupt β-amyloid aggregation than catechol,
likely due to additional hydrogen bonding and increased electronic reactivity. These insights
are crucial for developing therapeutic strategies targeting β-amyloid aggregation in Alzheimer's
disease, emphasizing the importance of molecular interactions in modulating peptide
stability and toxicity.
The study also provides a comparative analysis of the electronic properties and interaction dynamics
of the compounds, which can guide future research in the design of β-amyloid inhibitors.
The utilization of advanced simulation techniques underscores the potential for computational
methods in understanding complex biological interactions and developing novel therapeutic
agents. Furthermore, the insights into the differential effects of hydrophobic interactions versus
hydrogen bonding offer valuable information for the synthesis of new compounds aimed at mitigating
β-amyloid toxicity.
Verification of Qianlong Shutong Formula in the Treatment of Benign
Prostatic Hyperplasia
Authors: Zhang Ze-chao , Zhu Min , Huang Shu-ping , Wei Zhi-feng , Chen Yu , Shang Chang-jie
Published: January 2025

Aims:

To investigate the mechanisms through which Qianlong Shutong Formula
(QLSTF) exerts its effects on the management of benign prostatic hyperplasia (BPH).

Background:

BPH is a prevalent condition among older men and poses significant management challenges due to the limited effectiveness and potential side effects associated with current treatment options. QLSTF, a traditional Chinese medicine, has been utilized in the treatment of BPH; however, its mechanism of action remains inadequately understood.

Objective:

This study aimed to identify potential therapeutic targets of QLSTF for the management of BPH through the application of network pharmacology and subsequent experimental
validation.

Methods:

QLSTF compounds were identified utilizing liquid chromatography-mass spectrometry (LC-MS). Potential targets of QLSTF, as well as BPH-related targets, were retrieved from
public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were
acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as
the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.
Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro and in vivo experiments were conducted to further verify the findings.

Results:

A total of 52 bioactive ingredients of QLSTF and 760 QLSTF-BPH-related targets
were screened. Bioinformatics analysis revealed that Afzelin, Ononin, Glycitin, Emodin and
Erythritol may be potential candidate agents. AKT1, SRC, STAT3, GRB2, HRAS, MAPK3,
PIK3CA, PIK3R1, HSP90AA1, and EP300 could become potential therapeutic targets. PI3KAKT signaling pathway might play an important role in QLSTF against BPH. Moreover, molecular docking suggested that Afzelin, Ononin, Glycitin, Emodin, and Erythritol combined well
with AKT1, SRC, STAT3, HRAS, MAPK3, PIK3CA, and PIK3R1, respectively. In vitro and in
vivo experiments showed that QLSTF could inhibit the proliferation of cells, as well as the
PI3K-Akt signaling pathway, which further confirmed the prediction by network pharmacology
strategy and molecular docking.

Conclusions:

QLSTF may exert its therapeutic effects on BPH by modulating the PI3K/AKT
signaling pathway and inhibiting glandular hyperplasia. This study offers valuable insights into
the therapeutic targets of QLSTF in the management of BPH.
Bioinformatics Analysis of Lactylation-Related Biomarkers and Potential Pathogenesis Mechanisms in Age-Related Macular Degeneration
Authors: Gui Chenwei , Gao Yan , Zhang Rong , Zhou Guohong
Published: January 2025

Background:

Lactylation is increasingly recognized to play a crucial role in human
health and diseases. However, its involvement in age-related macular degeneration (AMD) remains
largely unclear.

Objective:

The aim of this study was to identify and characterize the pivotal lactylation-related
genes and explore their underlying mechanism in AMD.

Methods:

Gene expression profiles of AMD patients and control individuals were obtained and integrated
from the GSE29801 and GSE50195 datasets. Differentially expressed genes (DEGs)
were screened and intersected with lactylation-related genes for lactylation-related DEGs. Machine
learning algorithms were used to identify hub genes associated with AMD. Subsequently,
the selected hub genes were subject to correlation analysis, and reverse transcription quantitative
real-time PCR (RT-qPCR) was used to detect the expression of hub genes in AMD patients and
healthy control individuals.

Results:

A total of 68 lactylation-related DEGs in AMD were identified, and seven genes, including
HMGN2, TOP2B, HNRNPH1, SF3A1, SRRM2, HIST1H1C, and HIST1H2BD were selected as
key genes. RT-qPCR analysis validated that all 7 key genes were down-regulated in AMD patients.

Conclusion:

We identified seven lactylation-related key genes potentially associated with the progression
of AMD, which might deepen our understanding of the underlying mechanisms involved
in AMD and provide clues for the targeted therapy.
The Role of Lactate in Ischemic Stroke: As an Energy Source and Signaling Molecule
Authors: Zhang Rui , Li Xintong , Liu Kemeng , Yang Meng , Dong Peiliang , Han Hua
Published: January 2025

Stroke is an acute cerebrovascular disease that causes brain tissue damage due to sudden
blockage or rupture of blood vessels in the brain. According to the latest data from the Global
Burden of Disease Study, the number of stroke patients worldwide is estimated to exceed 100 million,
and more than 80% of patients suffer from stroke. Ischemic stroke is a type of stroke due to
which two-thirds of the patients are disabled or even die, seriously affecting the patient's quality
of life. Lactate is an indispensable substance in various physiological and pathological cells and
plays a regulatory role in different aspects of energy metabolism and signal transduction. Studies
have found that during cerebral ischemia and hypoxia, lactate concentration increases significantly,
improving the energy supply to the ischemic area. Based on the scientific concept of lactate
travelling through the brain, this article focuses on the important role of lactate as an energy
source after ischemic stroke and analyzes the relationship between lactate as a signaling molecule
and neuroprotection, angiogenesis, and anti-inflammatory effects. The aim of this study is to outline
the molecular mechanisms by which lactate exerts its different effects in ischemic stroke.
Some references are provided in this study for the research on lactate therapy for ischemic stroke.
Protein Misfolding and Aggregation of Pathological Igg Light Chains in Oncohematological Dyscrasias: From Molecular Pathways to Clinical
Implications
Authors: Guman Tomáš , Sýkora Ján , Demčáková Veronika , Žoldák Gabriel
Published: January 2025

Neoplastic transformation of B cells of the post-germinative center can lead to oncohematological
dyscrasias, which often results in an abnormal production of monoclonal immunoglobulin
light chains. The non-physiological production of large amounts of IgG light chains leads to
the formation of extracellular deposits called 'aggregomas' and rare conditions such as light chain
crystal deposition disease. Kidney manifestations and heavy-chain deposition disease can also occur
in plasma cell dyscrasias, emphasizing the role of IgG misfolding and aggregation. This
minireview describes molecular mechanisms of IgG light-chain aggregation, as well as the consequences
and therapeutic implications of IgG light chain misfolding in these disorders. By elucidating
the mechanisms of IgG light chain misfolding and aggregation, researchers can identify specific
molecular and cellular pathways. This knowledge opens the door to novel therapeutic targets, offering
the potential for interventions that can either prevent the initial misfolding events, promote
the proper folding and processing of immunoglobulins, or enhance the clearance of misfolded proteins
and aggregates. These protein folding-related issues persist even after the successful elimination
of the malignant B cells. Such targeted protein-folding therapies could significantly improve
patients' quality of life and contribute to their recovery. Thus, a deep understanding of IgG light
chain misfolding and its consequences not only sheds light on the complex biology of oncohematological
dyscrasias but also opens the way for innovative treatment strategies that could transform
patient care in these conditions, instilling hope and motivation in the healthcare professionals and
researchers in this field.
Benzopyrene Aggravates Nonalcoholic Liver Fatty Diseases in Female Mice Via the AHR/ERα Axis
Authors: Wu Yongkang , Xie Jing , Tao Qing , Tan Lina , Zhu Xiangyu , Yong Jin
Published: January 2025

Objective:

Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver
condition worldwide, and the statistics show that men have a higher incidence and
prevalence than women, but its toxicological mechanism is not completely clear. This
research is intended to explore the role of BaP in NAFLD and to study how the
environmental pollutant BaP influences the AHR/ERα axis to mediate the progression
of NAFLD.

Methods:

In this study, we established NAFLD models in vivo and in vitro by treating
HepG2 cells with a high-fat diet and Oleic acid (OA) in C57BL/6J mice. Liver injury
indexes ALT, AST, and lipid metabolism indexes TG and TC were evaluated to verify
the success of modeling. Then, the model was treated with BaP, and the mRNA and
protein expressions of CYP1A1, ERα, and SREBP-1c were evaluated by RT-PCR and
WB, and the changes of liver fat were evaluated by HE and oil red O staining. Next,
BaP was added into the cells treated with or without estradiol (E2), and the lipid
metabolism in the cells was evaluated by oil red O staining, and whether the above
levels of CYP1A1, ERα and SREBP-1c were changed.

Results:

Our results show that after exposure to BaP, ERα protein levels in mice and
cells are inhibited, mRNA and protein levels of SREBP-1c are reduced, and lipid
metabolism processes are obstructed. The addition of E2 can reduce the increase of
SREBP-1c mRNA and protein expression induced by OA, and reduce the deposition of
lipids in cells. However, BaP treatment can weaken the action of E2 and destroy the
protection of E2 in cells.

Conclusion:

The results showed that E2 could reduce SREBP-1c mRNA and protein
levels. BaP can stimulate AHR, leading to the degradation of ERα protein, reducing the
binding of E2 to ERα, and aggravating the progression of NAFLD. This reveals the
toxicological mechanism by which environmental pollutant BaP influences E2 to
mediate NAFLD, and provides strong evidence for differences in NAFLD between the
sexes.
DSPE-mPEG2000-Modified Podophyllotoxin Long-Circulating Liposomes
for Targeted Delivery: Their Preparation, Characterization, and
Evaluation
Authors: Zhang Langlang , Li Rongyu , Zhang Han , Suo Xubin , Guo Bohong
Published: January 2025

Objective:

DSPE-mPEG2000 is a phospholipid and polyethylene glycol conjugate used in
various biomedical applications, including drug delivery, gene transfection, and vaccine delivery.
Due to the hydrophilic and hydrophobic properties of DSPE-mPEG2000, it can serve as a drug carrier, encapsulating drugs in liposomes to enhance stability and efficacy.

Method:

In this study, long-circulating podophyllotoxin liposomes (Lc-PTOX-Lps) were prepared
using DSPE-mPEG2000 as a modifying material and evaluated for their pharmacokinetics and anticancer activity

Result:

Lc-PTOX-Lps had an encapsulation rate of 87.11±1.77%, an average particle size of
168.91±7.07 nm, a polydispersity index (PDI) of 0.19±0.04, and a zeta potential of -24.37±0.36 mV.
In vitro release studies showed that Lc-PTOX-Lps exhibited a significant slow-release effect. The
long-circulating liposomes demonstrated better stability compared to normal liposomes and exhibited
a significant slow-release profile. Pharmacokinetic studies indicated that Lc-PTOX-Lps had a prolonged half-life, reduced in vivo clearance, and improved bioavailability. Additionally, Lc-PTOX-Lps
exhibited better anticancer effects on MCF-7 cells and lower toxicity to normal cells compared to
PTOX.

Conclusion:

Lc-PTOX-Lps were synthesized using a simple and effective method, and Lc-PTOXLps are promising anticancer agents.