bluuebunny/crossref_metadata_2025 huggingface dataset:
PEMBELAJARAN PENDIDIKAN AGAMA ISLAM ABAD 21 PRESPEKTIF KITAB AL ARBAâ€™IN AN NAWAWIYAH
Authors: Rahmat Rahmat
Published: November 2023

Learning is a central activity in educational practice. In its implementation, learning must be carried out with correct implementation managerial steps such as having to go through planning, implementation to evaluation. In the 21st century, Islamic learning is required to be able to innovate in explaining learning terms and especially these activities in starting through a study of the turots books (books of inheritance) of previous scholars so that learning can continue to be developed while at the same time preserving the heritage of the scholars. This study applies a type of qualitative research with a literature review approach, which then from the results of the study of 12 hadiths in the book of Al-Arba'in An-Nawawiyah found learning procedures that are very relevant to be applied in 21st century Islamic learning in which the twelve hadiths contain affirm and strengthen learning procedures such as, 1) Learning strategies, 2) Models, 3) Approaches, 4) Materials, 5) Methods, 6) Techniques, 7) Media, 8) Evaluation, and 9) Remedial.Keywords: learning, Islamic education, 21st Century, Al-Arba'in An-NawawiyahÂ Abstrak Â Pembelajaran merupakan aktivitas sentral dalam praktik pendidikan. Secara implementasinya, pembelajaran haruslah dilaksanakan dengan langkah-langkah manajerial pelaksanaan yang benar seperti harus melalui perencanaan, pelaksanaan hingga evaluasi. Pada abad 21 ini, pembelajaran Islam dituntut untuk dapat berinovasi dalam menjelaskan istilah-istilah pembelajaran dan terutama kegiatan tersebut dalam dimulai melalui telaah kitab-kitab turots (kitab warisan) para ulama terdahulu agar pembelajaran dapat terus diupayakan pengembangannya sekaligus dapat melestarikan kitab warisan ulama tersebut. Penelitian ini menerapkan jenis penelitian kualitatif dengan pendekatan kajian kepustakaan, yang kemudian dari hasil telaah 12 hadis dalam kitab Al-Arbaâ€™in An-Nawawiyah ditemukan prosedur pembelajaran yang sangat relevan untuk diterapkan dalam pembelajaran Islam abad 21 yang mana keduabelas hadis tersebut kandungannya mempertegas dan menguatkan prosedur pembelajaran seperti, 1) Strategi pembelajaran, 2) Model, 3) Pendekatan, 4) Materi, 5) Metode, 6) Teknik, 7) Media, 8) Evaluasi, dan 9) Remidial.Kata Kunci: pembelajaran, pendidikan agama Islam, Abad 21, Al-Arba'in An-Nawawiyah
METODE ALFATIH: SEBUAH INOVASI DALAM PEMBELAJARAN KITAB KUNING DI PONDOK PESANTREN
Authors: Ruslan  , Hotibatul Ummah
Published: November 2023

The existence of an Islamic boarding school cannot be separated from learning the yellow book. However, learning the yellow book often leaves problems. This paper aims to describe : 1) the implementation of learning the yellow book through the Alfatih method at the Sumber Mas Islamic Boarding School, Almadinah Region, West Rombiya Village, Ganding District, Sumenep Regency along with the advantages and disadvantages of the Alfatih method. This study uses a qualitative research approach with a type of case study. Data collection techniques were carried out using interviews, observation, and documentation. The data analysis technique is done by three stages, namely data condensation, data display, and drawing conclusions/verification. The research findings show that: 1) the implementation of learning the yellow book through the Alfatih method at the Sumber Mas Islamic Boarding School, Almadinah Region, Ganding District, Sumenep Regency is carried out in 3 (three) stages, namely the initial stage, the core stage, and the final stage; 2) the advantages of the Alfatih method in learning the yellow book include the use of MLT, can be applied optimally and can be minimal, no need to memorize definitions, not complicated Nahwu and Sharraf, simple in various aspects, accustomed to reading the yellow book. While the shortcomings of the Alfatih method are that they are not used to writing and the book is incomplete.
PANDANGAN ISLAM TERKAIT GAYA HIDUP HEDONISME PADA GENERASI Z
Authors: Herlina Erna Rika
Published: November 2023

Hedonism is a view of life that assumes a person will feel happy if it is done by seeking pleasure or happiness as much as possible. This research is motivated by an attitude or lifestyle of hedonism which states that pleasure is here to be enjoyed and is the purpose of human life in this world. At first only certain people could have this hedonistic attitude and lifestyle, considering that to carry out this hedonistic attitude it required a lot of funds to be spent. However, in the end this attitude has spread to people from other circles even though they are in poor living conditions. At this time the hedonism lifestyle is mostly practiced by generation z because it is considered a pride to have this hedonistic lifestyle. Islam certainly strongly rejects this hedonistic attitude as a form of prohibition from extravagant and extravagant attitudes. Islam teaches that life is better if lived with simplicity. According to the view of Islam as a Muslim should use his wealth for useful things and not used for useless things. Â Keywords: lifestyle, hedonism, generation z, Islamic view
ANALISIS PENGARUH HARGA DAN KUALITAS PRODUK TERHADAP MINAT BELI KAIN TENUN BIMA DI MUTMAINAH KOTA BIMA
Authors: Iyelda Nafisa , Syaframis Nur Fetiningsih , Ariyanto Yogi
Published: November 2023

This study aims to determine the analysis of the effect of price and product quality on buying interest in Bima woven fabrics in Mutmainah Kota. The population used in this study were consumers at Mutmainah Kota Bima, with a total of 50 respondents. The method used in this study is multiple linear regression analysis. With the help of Microsoft Excel and the SPSS 23 software. The independent variables of this study are price (X1) and product quality (X2). The variable attached to this research is buying interest (Y). The results of this study indicate that the price, promotion and quality of the product. simultaneous influence on buying interest.
PENINGKATAN HARGA SAHAM MELALUI UKURAN PERUSAHAAN, PERTUMBUHAN PENJUALAN DAN PROFITABILITAS
Authors: Citra Prengki Kurnia Minang , Ristiyana Rida , Taufik Ruhiyat
Published: November 2023

Penelitian bertujuan untuk mengkaji peningkatan harga saham melalui ukuran perusahaan, pertumbuhan penjualan dan profitabilitas pada perusahaan sub sektor otomotif dan komponen yang terdaftar di BEI periode 2015-2019 dengan melibatkan 13 perusahaan dan total observasi sebanyak 60 perusahaan. Metode analisis data menggunakan regresi linier berganda. Hasil penelitian menemukan ukuran perusahaan, earnings per share berpengaruh positif dan signifikan terhadap harga saham, ini artinya ukuran perusahaan, earnings per share mampu menaikkan harga saham. Return on Equity berpengaruh negatif terhadap harga saham, ini berarti return on equity juga dapat meningkatkan harga saham. Pertumbuhan penjualan tidak berpengaruh terhadap harga saham, ini berarti pertumbuhan penjualan tidak mampu menaikkan harga saham
PENGARUH KEPEMIMPINAN DAN BUDAYA ORGANISASI TERHADAP KINERJA PEGAWAI (Studi Pada Karyawan Unit Donor Darah PMI Kabupaten Tangerang)
Authors: Setiawati Fitri , Bastian Asep Ferry
Published: November 2023

Setiap organisasi atau perusahaan memiliki budaya organisasi yang berfungsi untuk membentuk aturan atau pedoman dalam berpikir dan bertindak untuk mencapai tujuan yang telah ditetapkan bersama melalui kebijakan pimpinan perusahaan yang akan menghasilkan budaya organisasi pada perusahaan, harapannya agar kinerja pegawai meningkat. Tujuan dari penelitian ini adalah untuk mengetahui seberapa besar pengaruh kepemimpinan dan budaya organisasi terhadap kinerja pegawai. Populasi penelitian sebanyak 90 dan sampelnya menggunakan teknik simple random sampling menjadi sebanyak 50 pegawai pada UTD PMI Kabupaten Tangerang. Metode penelitiannya menggunakan deskriptif kuantitatif dengan analisis regresi. Hasil penelitiannya adalah Kepemimpinan berpengaruh signifikan terhadap kinerja pegawai, Budaya organisasi berpengaruh signifikan terhadap kinerja pegawai, Kepemimpinan dan budaya organisasi cecara bersama-sama berpengaruh signifikan terhadap kinerja pegawai. Penelitian ini dapat membuka jalan untuk meningkatkan kinerja pegawai dalam menghadapi era revolusi industri 4.0.
Aplikasi Technology Acceptance Model (TAM) Terhadap Pengguna Layanan Internet Banking di Kota Tangerang
Authors: Nuraini Luthfi
Published: November 2023

Penelitian ini bertujuan untuk menjelaskan Perceived Useflness dan Perceived Ease of Use terhadap tindakan menggunakan internet banking. Kerangka konseptual telah dikembangkan dan mengacu pada teori akseptasi model (TAM). Kuesioner telah dikembangkan dan disebarkan kepada 300 responden yang semuanya adalah pengguna internet banking. Metode penelitian yang digunakan pada survey ini adalah Metode Peneltian Deskriptif Kuantitatif. Kerangka sampling yang digunakan dalam survei ini didistribusikan ke pengguna internet banking. Jadi dalam pengumpulan data primer, peneliti mendistribusikan 300 kuesioner dengan 300 responden. Teknik sampling yang digunakan dalam penelitian ini adalah non probability sampling dengan jenis teknik convinience Sampling. Teknik analisis data yang digunakan pada penelitian ini adalah dengan menggunakan SEM (Structural Equation Model) dengan program AMOS (Analysis of Moment Structure).
Impact of Climate Change on the Dendroflora of Okhchuchay Area of Zangilan District
Authors: Hasanova M. , Maharramov S. , Asadov G. , Gaziev A. , Iskandarov S. , Mirjalally I.
Published: November 2023

Monitoring was carried out in Okhchuchay area of Zangilan district, and scientific research works were carried out in the surrounding areas of Agali village, Beshdeli village, Kechikli, Mammadbeyli, and Dagustu park. The aim was to study the impact of climate variability on biodiversity, to investigate the taxonomic composition of natural and cultivated dendroflora, bioecological characteristics. The natural dendroflora in Okhchuchay area of Zangilan district was studied, notes were made on the study of the modern state of plant species and analyzes were made in the direction of studying the role of biodiversity in ensuring the natural regeneration of rare species. Distribution areas of relict, endemic rare and endangered plants, economically important plants in Okhchuchay area of Zangilan district have been determined. Soil water samples were taken from the research area and its composition was investigated.
Energy Transition Policy and Forest Protection in the Republic of Mali and Azerbaijan: Analysis of Potentialities and Assets for Sustainable Development
Authors: Togola A.
Published: November 2023

The energy transition is a challenge and an urgency for the world facing the scarcity of fossil fuels and their impacts in the ecosystems by climate change. Through this study, we wanted to assess the potential of new and renewable energies in the Republic of Mali and Azerbaijan in view of their promotion for the preservation of forest areas, in a world facing the challenges of global warming. The methodology was based on documentary collection and documentary exploitation and analysis of cartographic data, tables and other figures. The study revealed to us the high frequency of the potential of these so-called energies, especially solar in Mali and hydraulic, wind and solar in Azerbaijan and the commitment of the authorities of these States to promote the energy transition but also the dependence of these States on fossils such as: oil and gas. The Republic of Azerbaijan exports fossil fuels and Mali depends on imports. The transition to alternative energy resources will undeniably make it possible to reduce greenhouse gas emissions at the global level and to preserve forest ecosystems in both countries.
Compilation of Land Evaluation Open Scales of Mountain Shirvan Cadastral District and Their Distribution by Land Plots
Authors: Khalilov A. , Rustamov S. , Gasimov A. , Bayramova P. , Abilova K. , Alieva T.
Published: November 2023

Data are provided on assessing the soil fertility in one district of Azerbaijan. When conducting a qualitative assessment of the lands of the Mountain Shirvan cadastral district, we relied on methodological guidelines that were developed for this area. To calculate the quality score of soil varieties, correction factors were used for the degree of their salinity, alkalinity, erosion, cultural state, etc. The main, detailed and final quality scales were compiled, the weighted average scores and the coefficient of comparative merit of the quality of lands in a given territory were calculated. Based on the results of calculations, open scales of land quality in the Mountain Shirvan cadastral district and their distribution among land plots were compiled. Correction coefficients for various soil characteristics are presented in the work.
Study of Baking Quality and Determination of High Molecular Weight Glutenin Subunits (HMW-GS) of Local and Introduced Wheat Varieties
Authors: Poladova G. , Akperov Z. , Gasanova G.
Published: November 2023

The baking qualities of 36 varieties of wheat are considered. Storage proteins — high molecular weight glutenin subunits (HMW-GS) — were studied. Electropherograms were processed in the GelPro Analyzer 4.0 computer program. The molecular weight of glutenin subunits was determined according to the method of G. Galili, M. G. Feldman using a marker variety. The quality of glutenin was assessed in points according to the method of O. Lukov. The bread was baked using the straight method, in accordance with the generally accepted method of laboratory baking; the fermentation of the dough and further baking were carried out on Domino and Arianna devices. As a result of the research, it was revealed that only 7 test samples (Askeran, Azemetli 95, Gonen, Gyrmyzy Gul, Nurlu99, Tale38, Ugur) with a null allele, having subunit 1 (Glu-A1a allele), have a fragment of 344 bp in size, in the remaining 29 samples encoded by the Glu-A1 locus, having subunit 2* (Glu-A1b allele), a fragment of 362 bp in size is amplified. The presence of a null allele does not always have a negative effect on baking quality. The reason for this remains to be determined.
Development Dynamics of Punica Diseases in Absheron District of Azerbaijan
Authors: Hasanli I.
Published: November 2023

The article describes the dynamics of the development of diseases of Punica in Absheron district. According to the methodology, visual inspection (5-25) of leaves, branches and fruits was carried out on 4 sides of the tree sample. Recorded samples of flower leaves, branches, stem bark and infected fruits were delivered to the laboratory; signs of the presence of pests and diseases: darkening, puncturing, spotting, drying, rotting, wilting, etc. Microscopic analyzes were carried out to determine species composition by recording characteristics. Using the method, the species composition of pomegranate mushroom seedlings was determined. Disease samples collected and delivered to the laboratory were analyzed according to the relevant methodological rules. A photograph of the pathogenic fungus spores was taken under a microscope. Under laboratory conditions in a thermostat, the development of ascospores of perithecia of the Sphaceloma punicae Bitanc. et Jenkins, which is a widespread disease of pomegranate, was partially controlled. When studying the spread of diseases affecting pomegranate plants in the region, route observations were carried out 3 times at 4-5 stations in the region at different stages of the growing season. At this time, visual observations were made of pomegranate bushes planted in different places (private courtyards and other enterprises, parks and roadsides).
Epizootological Features of Anoplocephalatoses of Small Cattle in Nakhchivan
Authors: Mammadov E. , Seyidli M.
Published: November 2023

In 2019-2021 studying of contamination of small cattle with anoplocephalides in various farm of Nakhchivan is carried out. It is ascertained anoplocephalatoses of small cattle are widespread. Disease of small cattle is observed in all districts. The species compositions of anoplocephalides of small cattle in the territory includes 5 species: Moniezia expansa (Rudolphi, 1805), Moniezia alba (Perroncito, 1878), Moniezia benedeni (Moniez, 1879), Avitellina centripunctata(Rivolta, 1874) and Thysaniezia giardi (Moniez, 1879). Extensive of invasion by results of helminthological dissections — 22.52%. Intensity of invasion of small cattle with anoplocephalides is on the average 3.7±0.3 spec/h.
History of Reconstructive Vascular Surgery
Authors: Zholborsov A. , Baisekeev T. , Niyazov A.K. , Mamyshov A. , Niyazov A.A. , Zhynzhyrov B. , Osmonbekova N.
Published: November 2023

This article reflects the history of the development of reconstructive surgery of vascular surgery. From the history it has been found out that reconstructive vascular surgery has achieved certain achievements and was a young branch of clinical surgery. Reconstructive surgery made it possible to continue life with severe vascular pathologies, which in most cases lead to death. The article reflects various clinical cases after certain methods of treatment, after which there are positive results. The history of the literature review describes the methods of surgery performed by various authors, who laid the foundation for reconstructive surgery and their invaluable experience, testifies to truly inexhaustible possibilities for continuing the path of vascular surgery.
Elegance in Pixels: Current Trends in Computer-aided Ornament Design
Authors: Obetkovskaya M. , Korobtseva N.
Published: November 2023

Current trends in the field of computer-aided design of ornaments are considered, as well as trends in changes in the perception of ornaments and the creation of decorative elements. It is noted that one of the trends is the fusion of traditions and innovations. Creative rethinking of age-old traditions in ornamentation is taking place today based on the use of modern computer technologies. The development of the field of parametric design, the use of algorithms and mathematical equations to create complex, intricate patterns and structures leads to the emergence of qualitatively new patterns that cannot be repeated by hand. The advent of 3D printing and additive manufacturing has revolutionized the creation of jewelry, and it has become possible to physically implement digital designs. Rapidly developing neural networks like Midjourney, Playground AI, DiffusionBee, DALL-E 2, Fy! Studio, etc. allow you to generate objects and use them as innovative sources of creative inspiration. The article provides examples of idea generation proposed by the authors in several neural networks. The world of ornamental design is experiencing a digital renaissance driven by the integration of technology and creativity. Through the fusion of tradition and innovation, parametric design, 3D printing, generative design and a commitment to sustainability, computer-aided ornament design is blossoming like never before. Thus, computer-aided design of patterns has turned fashion into a dynamic and innovative field where tradition meets technology. There are new opportunities for designer creativity, sustainability, and personalization of fashion. As digital age technology evolves, we can expect to continue to shape new ways of making clothes and expressing our-selves creatively.
Development of a Modern Website for the Department of Information Technologies and Management
Authors: Turdubaeva Zh. , Ismanov O.
Published: November 2023

The main feature of the development of the department’s website is the service for teaching students, teachers, and useful information for new ones. This article discusses the main aspects of the website of the Department of Information Technologies and Management of the Osh Technological University. The process of designing and implementing a website is also discussed. The most important parameter of the site is accessibility and ease of use, which is achieved using web technologies. The hypertext markup language HTML was used to develop the interface. And from the framework we used bootstrap.
Implementation of the Communicative Method in Russian Language Lessons in a Kyrgyz School
Authors: Chepekova G. , Segizbaeva N.
Published: November 2023

The article describes the implementation of the communicative method in teaching Russian as a second language. The communicative method is currently one of the effective methods of teaching language. It is aimed at developing the communicative competence of students. Communicative competence, in turn, includes linguistic, speech and sociocultural competence. The development of these components at the proper level indicates the formation of students’ communicative competence. The need to use the communicative method when teaching the Russian language in a Kyrgyz school is noted in the Subject Standard for the Russian language for grades 5-9 of general education organizations of the Kyrgyz Republic (for schools with Kyrgyz, Uzbek, and Tajik languages). As an example, an example of a lesson on the Russian language for the 8th grade of a school with the Kyrgyz language of instruction is given on the topic “Why do we study Russian. Coordinating communication” using the communicative method. Comments are given for each stage of the lesson.
Ways and Means of Using the Laboratory During the Chemistry Lesson
Authors: Baktiyarova S.
Published: November 2023

This article reveals the meaning, methods and means of laboratory classes on the subject of chemistry, namely: the main ways of learning the basics of chemistry, the significance of the experimental results obtained by students, stimulating their thinking, forcing them to discuss with each other and draw conclusions together, satisfying their interest students, it is always believed that scientific research is the best opportunity for the researcher, the role of the teacher and laboratory experiments are necessary experiments in order for students to live and work independently in the future.
Individual Educational Resource of a First Grade Student as a Means of Its Socialization
Authors: Zholdoshbaeva A. , Zholdoshbaev D.
Published: November 2023

The article is devoted to the peculiarities of teaching primary schoolchildren in the context of the socialization process. The author examined such aspects as teaching aids, ways of perceiving information, the type of thinking being formed and the general model of teaching primary schoolchildren. The materials of the article will allow us to gain a deeper insight into the mechanisms of the emergence of value orientations of younger schoolchildren and to develop the methods necessary to correct them. Objectives of the study: to analyze the socialization of junior schoolchildren in general through the prism of one of its aspects — education, as well as to create a list of features of children’s education in the conditions of modern socio-cultural changes in Kyrgyz society. The paper presents the main results of an empirical study conducted among Osh school teachers teaching schoolchildren from grades 1 to 4. As a result, meaningful data was obtained that provides opportunities for a more in-depth study of the presented topics.
Analysis of Psychological Influence Methods in Interpersonal Relationships
Authors: Zholdoshbaev D. , Monokbaev A. , Izamamatov A.
Published: November 2023

The article provides theoretical knowledge about the culture of interaction when influencing a person, about types of communication directly or indirectly, about general, interpersonal, imperative communication, about the presence of a desire to manipulate, about the basic techniques of manipulation arising from her aggressive desires. Research objectives: to study ways of influencing the addressee through the manipulative method of psychological influence in personality management. Research materials and methods: T. Lyra’s technique was carried out for diagnosing “interpersonal relationships”, and a correlation analysis of this process was carried out using the Bass-Dark questionnaire to identify “aggressive states”. Research results: in the process of manipulative influence on people, in most cases people use the characteristics of dominance, authoritarianism, and forceful communication of their opinions.
Theoretical Study of the Stressors Influence in Sports Activity
Authors: Zholdoshbaev D. , Izamamatov A. , Monokbaev A.
Published: November 2023

Research relevance: the article presents a scientific and theoretical study of stressful experiences that arise during the activities of athletes and related stressors. Research objectives: study of stressors and their characteristics that affect the performance of athletes. Research objectives: study of stressors and their characteristics affecting the performance of athletes. Research materials and methods: this article theoretically analyzes the level of athletes’ tendency to stress, the factors influencing it and impact on sports activity, and presents practical recommendations and conclusions. Research results: experiment results showed that stress in athletes, its effect on the performance of athletes, found its own confirmation in the study. Conclusions: it is desirable to prevent and eliminate stress for the effective organization of sports events and achievement of success in sports.
Physical and Social Spaces Interactions: Rural-Urban Dynamics in New Constructions in Kyrgyzstan
Authors: Isakov B. , Abdykulova R. , Chimanova Zh.
Published: November 2023

In Kyrgyzstan’s evolving cultural landscape in post-Soviet time, rural and urban dynamics reveal a captivating story of adaptation. This study explores domestic spaces, specifically the ‘bathhouse’, ‘naves’, and toilet placement preferences in newly built houses. The traditional rural ‘bathhouse’ has ventured into urban settings, challenging established notions. Conversely, the urban ‘naves’ now thrive in remote rural areas, reflecting evolving cultural tastes. Toilet placement choices among new settlement residents exemplify the fusion of rural and urban influences, highlighting their ability to adapt rural culture to urban living. This research underscores Kyrgyzstan’s complex cultural identity, where tradition and modernity harmonize, transcending urban and rural boundaries.
On Human and Culture in the N. Berdyaev’s Philosophy of History
Authors: Urmanbetova Zh. , Nazarkulova A.
Published: November 2023

The article examines the philosophical-historical concept of N. A. Berdyaev as raising questions regarding man and his historical existence. This concept is revealed as a religious interpretation of the philosophy of history. In the context of the philosophical-historical interpretation of the meaning of human existence, the ideas of the philosophy of culture find their refraction. The emphasis is on the category of ‘historical’ as a special reality that cannot be divided into material and spiritual. The philosophy of history of N. Berdyaev, focused on understanding the individual fate, the fate of man, appears as the metaphysics of history. Importance is given to culture, which in the understanding of the philosopher is ahistorical, supra-historical, and this is its meaning, internal harmony with genuine existence.
Preclinical Promise and Clinical Challenges for Innovative Therapies Targeting Liver Fibrogenesis
Authors: Addissouky Tamer A. , Ali Majeed M. A. , El Tantawy El Sayed Ibrahim , Wang Yuliang , El Baz Ayman , Elarabany Naglaa , Khalil Ahmed A.
Published: November 2023

Liver fibrosis resulting from chronic liver injury can progress to cirrhosis and liver failure. Current treatments are limited, creating an urgent need for novel antifibrotic therapies. Multiple emerging approaches have shown preclinical promise in inhibiting liver fibrogenesis or stimulating regeneration, including artificial liver support, stem cell therapy, cell/gene therapy, nanomedicines, immunotherapy, and herbal medicines. Artificial liver support provides detoxification but has shown inconsistent transplant bridging benefits. Stem cell transplantation demonstrates antifibrotic paracrine effects and differentiation potential. Cell therapy with hepatocytes or modulatory immune cells, as well as genetic engineering approaches, aims to replace damaged cells or suppress inflammation. Nanoparticles enable targeted delivery of antifibrotic drugs and genes. Immunotherapy using checkpoint inhibitors, vaccines, or engineered cells can attenuate fibrogenesis-related inflammation. Some traditional Chinese herbal formulas and compounds exhibit antifibrotic, anti-inflammatory, and regenerative mechanisms. Despite encouraging preclinical data, most novel antifibrotic therapies have yet to achieve clinical translation, limited by challenges in safety, delivery, and efficacy. Combination treatment regimens may provide maximal therapeutic impact. Ongoing optimization and rigorous clinical evaluation are needed to develop effective new antifibrotic therapies for patients with chronic liver disease.
Chitosan-salvianolic acid B coating on the surface of nickel-titanium alloy inhibits proliferation of smooth muscle cells and promote endothelialization
Authors: Bi Shijun , Lin Hao , Zhu Kunyuan , Zhu Zechao , Zhang Wenxu , Yang Xinyu , Chen Shanshan , Zhao Jing , Liu Meixia , Pan Pengyu , Liang Guobiao
Published: November 2023

Introduction: Intracranial stents are of paramount importance in managing cerebrovascular disorders. Nevertheless, the currently employed drug-eluting stents, although effective in decreasing in-stent restenosis, might impede the re-endothelialization process within blood vessels, potentially leading to prolonged thrombosis development and restenosis over time.

Methods: This study aims to construct a multifunctional bioactive coating to enhance the biocompatibility of the stents. Salvianolic acid B (SALB), a bioactive compound extracted from Salvia miltiorrhiza, exhibits potential for improving cardiovascular health. We utilized dopamine as the base and adhered chitosan-coated SALB microspheres onto nickel-titanium alloy flat plates, resulting in a multifunctional drug coating.

Results: By encapsulating SALB within chitosan, the release period of SALB was effectively prolonged, as evidenced by the in vitro drug release curve showing sustained release over 28 days. The interaction between the drug coating and blood was examined through experiments on water contact angle, clotting time, and protein adsorption. Cellular experiments showed that the drug coating stimulates the proliferation, adhesion, and migration of human umbilical vein endothelial cells.

Discussion: These findings indicate its potential to promote re-endothelialization. In addition, the bioactive coating effectively suppressed smooth muscle cells proliferation, adhesion, and migration, potentially reducing the occurrence of neointimal hyperplasia and restenosis. These findings emphasize the exceptional biocompatibility of the newly developed bioactive coating and demonstrate its potential clinical application as an innovative strategy to improve stent therapy efficacy. Thus, this coating holds great promise for the treatment of cerebrovascular disease.
Advancements in engineered exosomes for wound repair: current research and future perspectives
Authors: Ye Hailian , Wang Feng , Xu Guangchao , Shu Feihong , Fan Kunwu , Wang Dali
Published: November 2023

Wound healing is a complex and prolonged process that remains a significant challenge in clinical practice. Exosomes, a type of nanoscale extracellular vesicles naturally secreted by cells, are endowed with numerous advantageous attributes, including superior biocompatibility, minimal toxicity, and non-specific immunogenicity. These properties render them an exceptionally promising candidate for bioengineering applications. Recent advances have illustrated the potential of exosome therapy in promoting tissue repair. To further augment their therapeutic efficacy, the concept of engineered exosomes has been proposed. These are designed and functionally modifiable exosomes that have been tailored on the attributes of natural exosomes. This comprehensive review delineates various strategies for exosome engineering, placing specific emphasis on studies exploring the application of engineered exosomes for precision therapy in wound healing. Furthermore, this review sheds light on strategies for integrating exosomes with biomaterials to enhance delivery effectiveness. The insights presented herein provide novel perspectives and lay a robust foundation for forthcoming research in the realm of cutaneous wound repair therapies.
Iron affects the sphere-forming ability of ovarian cancer cells in non-adherent culture conditions
Authors: Battaglia Anna Martina , Sacco Alessandro , Vecchio Eleonora , Scicchitano Stefania , Petriaggi Lavinia , Giorgio Emanuele , Bulotta Stefania , Levi Sonia , Faniello Concetta Maria , Biamonte Flavia , Costanzo Francesco
Published: November 2023

Introduction: Detachment from the extracellular matrix (ECM) is the first step of the metastatic cascade. It is a regulated process involving interaction between tumor cells and tumor microenvironment (TME). Iron is a key micronutrient within the TME. Here, we explored the role of iron in the ability of ovarian cancer cells to successfully detach from the ECM.

Methods: HEY and PEO1 ovarian cancer cells were grown in 3D conditions. To mimic an iron rich TME, culture media were supplemented with 100 μM Fe3+. Cell mortality was evaluated by cytofluorimetric assay. The invasive potential of tumor spheroids was performed in Matrigel and documented with images and time-lapses. Iron metabolism was assessed by analyzing the expression of CD71 and FtH1, and by quantifying the intracellular labile iron pool (LIP) through Calcein-AM cytofluorimetric assay. Ferroptosis was assessed by quantifying mitochondrial reactive oxygen species (ROS) and lipid peroxidation through MitoSOX and BODIPY-C11 cytofluorimetric assays, respectively. Ferroptosis markers GPX4 and VDAC2 were measured by Western blot. FtH1 knockdown was performed by using siRNA.

Results: To generate spheroids, HEY and PEO1 cells prevent LIP accumulation by upregulating FtH1. 3D HEY moderately increases FtH1, and LIP is only slightly reduced. 3D PEO1upregulate FtH1 and LIP results significantly diminished. HEY tumor spheroids prevent iron import downregulating CD71, while PEO1 cells strongly enhance it. Intracellular ROS drop down during the 2D to 3D transition in both cell lines, but more significantly in PEO1 cells. Upon iron supplementation, PEO1 cells continue to enhance CD71 and FtH1 without accumulating the LIP and ROS and do not undergo ferroptosis. HEY, instead, accumulate LIP, undergo ferroptosis and attenuate their sphere-forming ability and invasiveness. FtH1 knockdown significantly reduces the generation of PEO1 tumor spheroids, although without sensitizing them to ferroptosis.

Discussion: Iron metabolism reprogramming is a key event in the tumor spheroid generation of ovarian cancer cells. An iron-rich environment impairs the sphere-forming ability and causes cell death only in ferroptosis sensitive cells. A better understanding of ferroptosis sensitivity could be useful to develop effective treatments to kill ECM-detached ovarian cancer cells.
Higher oxidative balance score decreases risk of stroke in US adults: evidence from a cross-sectional study
Authors: Zhan Fangfang , Lin Gaoteng , Duan Kefei , Huang Bixia , Chen Longfei , Ni Jun
Published: November 2023

Background

The oxidative balance score (OBS) can be used to represent the overall burden of oxidative stress in an individual. This study aimed to explore the association between the risk of stroke and OBS.

Methods and materials

The National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 was used to extract a series of variables for participants who took the stroke questionnaire. The construction of OBS relied on diet and lifestyle components, which included 16 nutrients and 4 lifestyle factors. Weighted multivariable-adjusted logistic regression was performed to investigate the association between stroke risk and OBS. A stratified analysis was also conducted. The dose-response relationship between stroke risk and OBS was elucidated by performing a restricted cubic spline function.

Results

A total of 20,680 participants were included for analysis, 768 of whom suffered from stroke. Based on weighted multivariable logistic regression analysis, we discovered that the stroke prevalence decreased by 2% for each OBS unit added [OR: 0.98 (0.97–1.00), P < 0.01]. For the OBS subgroup, we also discovered that higher OBS was related to a reduction in the risk of stroke [Q4 vs. Q1: OR:0.65 (0.46–0.90), P < 0.01]. The prevalence of stroke declined by 3% with every OBS unit added to the diet component [OR: 0.97 (0.96–0.99), P < 0.01]. For the dietary OBS subgroup, higher OBS in diet components was associated with a decrease in the prevalence of stroke [Q4 vs. Q1: OR: 0.65, (0.47–0.91), P < 0.05]. Further stratified analysis showed that every OBS unit raised was associated with a decline in stroke prevalence, which was statistically significant in participants in subgroups of ≥60 years, female, no-diabetes mellitus and no-hypertension. OBS and stroke prevalence were correlated in a linear manner.

Conclusion

The study found that a higher OBS was associated with a decrease in stroke prevalence, which could be a significant indicator for evaluating stroke risk.
Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
Authors: Xue Chunchun , Luo Huan , Wang Libo , Deng Qing , Kui Wenyun , Da Weiwei , Chen Lin , Liu Shuang , Xue Yongpeng , Yang Jiafan , Li Lingxing , Du Wenlan , Shi Qi , Li Xiaofeng
Published: November 2023

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.
Conventional niche overlap measurements are not effective for assessing interspecific competition
Authors: Murray Dennis L. , Gobin Jenilee , Scully Arthur , Thornton Daniel H.
Published: November 2023

Interspecific competition is notoriously difficult to detect and quantify, especially in species that are wide-ranging or otherwise difficult to track in the wild. Research investigating interspecific competition usually relies on niche overlap measurements despite that this approach alone does not yield rigorous inference. As an illustration, we review published research assessing interspecific competition in mid-sized carnivores in North America (bobcat – Lynx rufus; Canada lynx – Lynx canadensis; coyote – Canis latrans), and report on shortcomings associated with commonly used study designs and types of inference. Niche overlap measurements typically focus on one or two resources (e.g., food, space, habitat), often using non-independent sampling units and inadequate replication. Few studies measure overlap variation through space, time, or resource variability, which is crucial for robust assessment. Niche overlap (or lack thereof) is used as evidence both for and against interspecific competition, reflecting a weak link between competition theory, predicted responses, and observations. Overall, challenges associated with conducting competition research in the field promote over-reliance on simple measurements, flawed study designs and weak inference. Minimally, niche overlap studies should include assessment across multiple niche dimensions and spatial or temporal variation in competitor density or resource availability. Dynamic investigative approaches should include new technologies for tracking inter-individual interactions, study designs that leverage quasi-experiments (e.g., decline in shared resources, biological control of one competitor), and synthetic analyses (e.g., meta-regression). Ultimately, better understanding of competition theory vis-à-vis study design and data needs will promote improved understanding of the role of interspecific competition in nature.
Fundamental but underrepresented: root carbon stocks in African montane forests
Authors: Yaffar Daniela , Addo-Danso Shalom D. , Powers Jennifer S. , Meier Ina C.
Published: November 2023

African montane forests harbor some of the greatest biodiversity worldwide, with high levels of species endemism. However, the loss of these forests through fragmentation, deforestation and climate change has been rapidly increasing in recent years. Montane forests in Africa are more susceptible to changes in climate than their lowland counterparts, yet their ecological value is still underrepresented. These montane forests have recently been highlighted as a major aboveground carbon (C) stock. The estimated 149.4 Mg C ha−1 from aboveground live trees surpasses estimates from the Intergovernmental Panel on Climate Change for these endangered forests, and exceeds reported values for neotropical montane and lowland forests by up to 70%. Despite the tremendous implications of these findings, coordinated and available research on the C storage potential of the other share of African montane forest biomass, that is in tree roots, is largely missing. Broadly estimated from the allometry of aboveground C stocks and from root:shoot ratios in lowland forests, more than 60 Mg C ha−1 can be stored in African montane forest roots, about 40% more than previously determined. While this broad estimation points at the potential importance of root C stocks in African montane forests, it also unveils a far-reaching knowledge gap. Here, we advocate for a more quantitative representation of the root C stock from dominant forest tree species of African tropical montane forests and ultimately for a better grasp on tree C stocks from this endangered ecosystem.
Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carrying Rag1 hypomorphic mutations
Authors: Castiello Maria Carmina , Di Verniere Martina , Draghici Elena , Fontana Elena , Penna Sara , Sereni Lucia , Zecchillo Alessandra , Minuta Denise , Uva Paolo , Zahn Marco , Gil-Farina Irene , Annoni Andrea , Iaia Silvia , Ott de Bruin Lisa M. , Notarangelo Luigi D. , Pike-Overzet Karin , Staal Frank J. T. , Villa Anna , Capo Valentina
Published: November 2023

Introduction

Recombination activating genes (RAG) 1 and 2 defects are the most frequent form of severe combined immunodeficiency (SCID). Patients with residual RAG activity have a spectrum of clinical manifestations ranging from Omenn syndrome to delayed-onset combined immunodeficiency, often associated with granulomas and/or autoimmunity (CID-G/AI). Lentiviral vector (LV) gene therapy (GT) has been proposed as an alternative treatment to the standard hematopoietic stem cell transplant and a clinical trial for RAG1 SCID patients recently started. However, GT in patients with hypomorphic RAG mutations poses additional risks, because of the residual endogenous RAG1 expression and the general state of immune dysregulation and associated inflammation.

Methods

In this study, we assessed the efficacy of GT in 2 hypomorphic Rag1 murine models (Rag1F971L/F971L and Rag1R972Q/R972Q), exploiting the same LV used in the clinical trial encoding RAG1 under control of the MND promoter.

Results and discussion

Starting 6 weeks after transplant, GT-treated mice showed a decrease in proportion of myeloid cells and a concomitant increase of B, T and total white blood cells. However, counts remained lower than in mice transplanted with WT Lin- cells. At euthanasia, we observed a general redistribution of immune subsets in tissues, with the appearance of mature recirculating B cells in the bone marrow. In the thymus, we demonstrated correction of the block at double negative stage, with a modest improvement in the cortical/medullary ratio. Analysis of antigenspecific IgM and IgG serum levels after in vivo challenge showed an amelioration of antibody responses, suggesting that the partial immune correction could confer a clinical benefit. Notably, no overt signs of autoimmunity were detected, with B-cell activating factor decreasing to normal levels and autoantibodies remaining stable after GT. On the other hand, thymic enlargement was frequently observed, although not due to vector integration and insertional mutagenesis. In conclusion, our work shows that GT could partially alleviate the combined immunodeficiency of hypomorphic RAG1 patients and that extensive efficacy and safety studies with alternative models are required before commencing RAG gene therapy in thesehighly complex patients.
Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup
Authors: Xu Huikang , Sheng Shiying , Luo Weiwei , Xu Xiaofang , Zhang Zhaocai
Published: November 2023

Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It is mainly manifested by non-cardiogenic pulmonary edema, resulting from intrapulmonary and extrapulmonary risk factors. ARDS is often accompanied by immune system disturbance, both locally in the lungs and systemically. As a common heterogeneous disease in critical care medicine, researchers are often faced with the failure of clinical trials. Latent class analysis had been used to compensate for poor outcomes and found that targeted treatment after subgrouping contribute to ARDS therapy. The subphenotype of ARDS caused by sepsis has garnered attention due to its refractory nature and detrimental consequences. Sepsis stands as the most predominant extrapulmonary cause of ARDS, accounting for approximately 32% of ARDS cases. Studies indicate that sepsis-induced ARDS tends to be more severe than ARDS caused by other factors, leading to poorer prognosis and higher mortality rate. This comprehensive review delves into the immunological mechanisms of sepsis-ARDS, the heterogeneity of ARDS and existing research on targeted treatments, aiming to providing mechanism understanding and exploring ideas for accurate treatment of ARDS or sepsis-ARDS.