bluuebunny/crossref_metadata_2025 huggingface dataset:
PARTISIPASI MASYARAKAT DALAM LAYANAN ANAK USIA DINI HOLISTIK-INTEGRATIF DI TK AL-MUKHLIS GARUT
Authors: Rahmat Ujang , Hufad Achmad , Ardiwinata Jajat S. , Robandi Babang
Published: June 2024

Penelitian ini bertujuan untuk menganalisis bentuk dan tingkat partisipasi masyarakat dalam layanan anak usia dini holistik-integratif di Tk Al-Mukhlis Kecamatan Tarogong Kaler Garut. Dengan pendekatan kuantitatif, penelitian ini bersifat deskriptif. Data yang diperoleh berdasarkan ex post facto diharapkan dapat menggambarkan secara tepat sifat-sifat individu, keadaan, gejala atau kelompok-kelompok tertentu atau menemukan penyebaran (frekuensi) suatu gejala dan gejala lainnya dalam masyarakat di Kampung Dukuh Kelurahan Pananjung Kecamatan Tarogong Kaler Kabupaten Garut, khususnya yang berasal dari unsur: yayasan persis, pendidik dan tenaga kependidikan Al Muklis, dan orang tua wali, yang selanjutnya ditetapkan sebagai sampel sebanyak 89 orang. Hasil penelitian menunjukkan bahwa: 1) TK Al Mukhlis telah menyelenggarakan program layanan anak usia dini holistik-integratif secara sistematis2) bentuk partisipasi masyarakat yang diberikan dalam layanan anak usia holistik-integratif pada ketiga tahapan, yakni sangat bervariasi dan mengalami perubahan. Bentuk partisipasi yang paling dominan diberikan masyarakat adalah berupa sumbangan ide atau pikiran; 3) tingkat partisipasi masyarakat yang diberikan dalam layanan anak usia holistik-integratif pada ketiga tahapan, cenderung meningkat pada setiap tahapannya. Hasil analisis menunjukkan dari tahap awal pelaksanaan kegiatan berupa perencanaan, yang selanjutnya diikuti dengan tahap pelaksanaan, sampai evaluasi program, tingkat partisipasi yang diberikan masyarakat secara perlahan meningkat, dari tangga yang lebih rendah yaitu consultation pada tahap perencanaan, meningkat satu tingkat menjadi placation pada tahap pelaksanaan, dan naik lagi setingkat lebih tinggi menjadi partnership pada tahap evaluasi program.
Pengaruh Komunitas Belajar Terhadap Kemampuan Pedagogik Guru Di Ikatan NSIN TK Bekasi
Authors: Khusna Rofiqotul , Priyanti Nita
Published: June 2024

Kemampuan pedagogik guru sangat variatif. Ada guru yang memiliki pedagogik yang baik dan sebaliknya. Kemampuan ini dapat mengalami perkembangan positif dengan adanya perhatian yang lebih besar, seperti mengikuti komunitas belajar. Kompetensi pedagogik guru PAUD masih rendah, sehingga mereka menghadapi tantangan dalam praktik mengajar yang monoton. Untuk mengembangkan kompetensi, keberadaan komunitas belajar dianggap penting bagi para guru. Komunitas belajar memberikan kesempatan bagi guru untuk berbagi pengalaman, bertukar ide, dan mengakses sumber daya pendidikan yang relevan. Tujuan penelitian untuk mengkaji pengaruh komunitas belajar terhadap kemampuan pedagogik guru. Metode yang digunakan ialah kuantitatif numerik dengan metode statistika. Data penelitian diproses dengan SPSS 25.0. Dilakukan uji validitas, reliabilitas, normalitas, dan linearitas sebelum pengujian hipotesis menggunakan regresi linear. Hasil penelitian menunjukkan nilai signifikansi (p-value) sebesar 0.007 atau 0.007 < 7.567, berarti H0 ditolak. Dari hasil tersebut dapat dijelaskan bahwa komunitas belajar memiliki pengaruh dan hubungan yang signifikan terhadap kemampuan pedagogik. Persamaan koefisien regresi menunjukkan bahwa pengaruh variabel "Komunitas belajar" terhadap kemampuan pedagogik adalah positif sebesar 0,296. Hasil penelitian ini menekankan pentingnya komunitas belajar dalam memengaruhi kemampuan guru dalam mengembangkan pedagogiknya. Melalui komunitas belajar, guru dapat berinteraksi dengan sesama guru dan berbagi pengalaman serta praktik terbaik, guru dapat mengembangkan kompetensinya dalam mengajar. Simpulan penelitian ini menunjukkan bahwa partisipasi dalam komunitas belajar memiliki pengaruh yang signifikan terhadap kemampuan pedagogik guru.
Praktik Pengasuhan: Responsif Genderkah Orangtua Kepada Anak di Dalam Keluarga?
Authors: Putra Ari , Hatimah Ihat , Wahyudin Uyu , Saripah Iip
Published: June 2024

Ketidakadilan gender pada anak laki-laki dan perempuan adalah isu yang kompleks dan harus diperangi secara kolektif oleh masyarakat dan pemerintah. Peran keluarga menjadi paling krusial dalam membentuk sikap yang responsive gender. Penelitian ini bertujuan untuk mendeskripsikan pengasuhan yang diberikan oleh orangtua dengan merujuk pada pertanyaan apakah orangtua responsive gender dalam aktivitas pengasuhan kepada anaknya yang berusia 0-6 tahun di SPNF Kabupaten Bengkulu Tengah. Responsive gender dalam hal ini adalah memberikan akses, partisipasi, control, dan peran kepada anaknya yang masih dalam kategori usia dini. Metode penelitian ini menggunakan pendekatan kualitatif. Partisipan dalam penelitian ini adalah orangtua yang mengikutsertakan anaknya dalam program pendidikan anak usia di SPNF-SKB Bengkulu Tengah berjumlah 3 keluarga dengan pola pengasuhan yang berbeda. Teknik analisis data penelitian ini menggunakan teknik analisis gender model harvard Analisis dilakukan dengan menggunakan butir kriteria kesejahteraan, akses, penyadaramn, partisipasi, dan penguasaan bagi laki-laki maupun perempuan. Hasil penelitian ini adalah pengasuhan yang dilakukan orangtua mengarah pada pengasuhan yang demokrasi dengan menerapkan fungsi harmonisasi keluarga sebagai pola dalam pengasuhan seimbang antara ayah dan ibu. Orangtua memberikan perhatian yang sesuai dengan kebutuhan anak dengan konsistensi dan sistemik tanpa melakukan tindakan membeda-bedakan perempuan dan laki-laki di dalam masyarakat sehingga langkah tersebut mampu menghapus kebudayaan yang mengarah pada ketidaksetaraan gender di dalam masing-masing keluarga.
Pengaruh Penambahan Nutrient (NPK dan Pupuk Urea) terhadap Bioethanol Hasil Fermentasi Biji Alpukat (Persea americana Mill.)
Authors: Putri Zakyya Septiana , Ruyani Aceng , Uliyandari Mellyta , Wardana Rendy Wikrama , Sukarso A. A.
Published: June 2024

Bioethanol is an energy source obtained through fermentation. In bioethanol production, Persea americana seeds are used as a fermentation medium because they contain lots of carbohydrates. This research aims to determine the effect of additional nutrients (NPK and urea fertilizer) required by Saccharomyces cerevisiae by varying the nutritional variables in the form of NPK and urea fertilizer. The process of making bioethanol goes through stages: making Persea americana seed flour, hydrolysis process using 6% HCl, then fermentation process, and distillation process. This research was carried out with the addition of Nutrients in the form of NPK and Urea Fertilizer with 5 treatments, namely: A) 100% yeast (no addition of Nutrients); B) 100% NPK (4 g); C) 100% Urea Fertilizer (4 g); D) 50% NPK and 50% Urea Fertilizer (4 g NPK and 4 g Urea Fertilizer); and E) 75% NPK and 25% Urea Fertilizer (3 g NPK and 1 g Urea Fertilizer), and varying the length of fermentation time to 13, 19, and 25 days. Success parameters are assessed through the bioethanol yield produced by each treatment. The research results showed that the highest bioethanol (29.7 ± 0.47%) was composition E (NPK 75% and Urea Fertilizer 25%) with a fermentation time of 25 days.
PEMBUATAN KATALOG PRODUK DIGITAL DI INSTAGRAM SEBAGAI MEDIA PROMOSI PADA KOPI LOKA
Authors: Amir Salsabila Pradipta , Muhammad Ashar
Published: June 2024

Revolusi digital telah mengubah secara fundamental cara kita hidup, bekerja, dan berinteraksi. Media sosial telah menjadi suatu kebutuhan masyarakat dalam berinteraksi. Hal ini mendorong para pelaku usaha coffee shop menggunakan media sosial sebagai media promosi. Salah satunya adalah Kopi Loka yang belum mengoptimalkan media sosial instagram untuk memperkenalkan produknya. Tujuan yang ingin dicapai dalam penelitian ini merancang katalog produk digital Instagram sebagai media promosi Kopi Loka. Metode yang digunakan dalam penelitian ini ialah metode deskriptif kualitatif untuk mendeskripsikan tentang strategi promosi melalui media sosial yaitu instagram dalam bentuk katalog produk digital di Kopi Loka. Hasil penelitian menunjukkan bahwa pemanfaatan katalog produk digital melalui instagram sebagai media promosi mampu meningkatkan daya tarik pengunjung yang datang ke Kopi Loka.
Vertical distribution of Pacific oyster Crassostrea gigas larvae and modeling larval transport in Hiroshima Bay, Japan
Authors: Onitsuka G , Abo K , Matsubara T , Mizuno Ki , Ikeda Si , Sato T , Shikata T , Onduka T , Hamaguchi M
Published: June 2024

Understanding vertical distribution of planktonic larvae is essential for elucidating larval dispersal and recruitment processes. We investigated the vertical distribution and horizontal transport of Pacific oyster Crassostrea gigas larvae by field observations and numerical simulations during their main spawning season in Hiroshima Bay, Japan. In field observations, despite horizontal differences and slight diurnal/semi-diurnal changes depending on larval sizes, most larvae were distributed in the upper 3 m layer. The relationship between C. gigas larvae and environmental conditions revealed that larval density increased with increasing temperature and chlorophyll a concentration, and the density peaked at salinity of approximately 20 for all larval sizes. The observed results suggest that the distribution characteristics of C. gigas larvae are suitable for survival in an estuarine area, where environmental conditions are potentially favorable but hydrodynamic conditions can drastically change over the short term due to variations in river discharge. To examine the effect of high river discharge on larval transport, numerical simulations were conducted using a particle-tracking model incorporating the vertical motion of C. gigas larvae. The simulation results reproduced the spatio-temporal dynamics of planktonic and settled larvae after the high river discharge. Although most particles simulating larvae outflowed from the main spawning area, an area of high particle density at the end of simulation corresponded with the offshore area for seedling collection. The present study suggests the role of vertical distribution of C. gigas larvae for recruitment, and the prospect of sustainability in oyster aquaculture with respect to seedling collection despite the frequent heavy rainfall associated with climate change.
Pemasangan Instalasi Penerangan dan Lampu Emergency di Musholla Nurul Fattah Desa Jago
Authors: Sigit Setya Wiwaha  , Muhammad Fahmi Hakim  , Rhezal Agung Ananto  , Ahmad Hermawan  , Yanik Lailinas Sakinah
Published: June 2024

Musholla Nurul Fattah berada di RT 12 RW 8 desa jago kecamatan tumpang kabupaten malang. Musholla ini dalam kesehariannya digunakan untuk ibadah sholat dan kegiatan lainnya, khusunya pada malam hari. Bangunan musholla Nurul Fattah baru saja direnovasi, namun dalam renovasi tersebut ada beberapa pekrejaan yang belum bisa diselesaikan salah satunya adalah mengganti instalasi listrik musholla. Disisi lain bahwa kondisi instalasi listrik musholla Nurul Fattah banyak instalasi lama yang berpotensi bahaya dan tidak sesuai standart. Ukuran luas penampang kabel tidak sesuai dengan standart yang berlaku, penyambungan kabel yang tidak aman dan membahayakan, kurangnya pencahayaan di tempat wudlu, dan jika terjadi pemadaman listrik tidak mempunyai penerangan cadangan, Jika ada pemadaman maka akan mengalami kegelapan dan kegiatan terhenti. Melihat kondisi tersebut diatas maka perlua kiranya untuk dilakukan instalasi ulang dan pemasangan lampu emergency di musholla Nurul Fattah desa Jago kecamatan Tumpang kabupaten Malang. Sehingga masyarakat sekitar muhollah dapat menjalankan ibadah dan kegiatan keagamaan dengan aman dan nyaman.
Sosialisasi Pengolahan Limbah Plastik Menjadi Pelet di Desa WringinSongo - Tumpang
Authors: Achmad Chumaidi  , Iswara Mochammad Agung Indra , Cucuk Evi Lusiani  , Abdul Chalim
Published: June 2024

Desa Wringinsongo merupakan wilayah yang menjadi desa mitra Politeknik Negeri Malang yang berada di Kecamatan Tumpang Kabupaten Malang. Dalam perkembangannya saat ini, permasalahan yang dihadapi oleh warga setempat adalah banyaknya timbunan sampah yang diakibatkan oleh banyaknya jumlah penduduk yang mendiami desa tersebut, munculnya pasar modern, serta meningkatnya pola hidup masyarakat. Salah satu pengelolaan dan pengolahan sampah rumah tangga adalah dengan cara memisahkan sampah organik dan non- organik, sampah organik diolah menjadi pupuk dan sampah non-organik yang didominasi sampah plastik dimana dapat diolah menjadi butir plastik/ pelet. Tim Pengabdian Masyarakat Jurusan Teknik Kimia Polinema memberikan sosialisasi mengenai teknik pengolahan sampah plastik menjadi butir plastik/ pellet. Masyarakat diberi pembekalan tata cara pengolahan dan pengelolaan sampah terlebih dahulu, kemudian masyarakat diberi pembekalan tentang keunggulan dan potensi ekonomi dari penjualan biji plastik/ pellet. Tampak masyarakat sangat antusias dalam mendengarkan sosialisasi tersebut, sehingga diharapkan lingkungan Desa Wringinsongo menjadi bersih dan meningkatkan produktivitas dan pendapatan daerah tersebut.
Pengenalan APE Matematika di PAUD Terpadu Siti Hajar Kelurahan Tunggul Wulung Kota Malang
Authors: Zainal Abdul Haris  , Widi Dwi Ernawati  , Subekhi Hadi Purnomo  , Futuh Handoyo  , Ari Kamayanti  , Anna Isrowiyah
Published: June 2024

Untuk memperoleh pemahaman tentang ide-ide matematika, siswa perlu untuk mengintegrasikan dan menghubungkan berbagai konsep dengan berbagai cara. Penggunaan alat peraga yang efektif dapat membantu siswa menghubungkan ide dan mengintegrasikan pengetahuan tersebut, sehingga siswa memperoleh pemahaman tentang konsep matematika. Siswa yang sedang belajar pada jenjang PAUD perlu mendapatkan pengetahuan penggunakan Alat Permainan atau Peraga Edukatif (APE) untuk mengenalkan suatu konsep, khususnya matematika. PAUD Terpadu Siti Hajar sebagai mitra memiliki lebih dari 100 siswa, akan tetapi memiliki APE khususnya yang menunjang pengenalan matematika sangat terbatas. Kegiatan pengabdian pada masyarakat ini dilakukan dengan mengenalkan matematika sejak usia dini pada siswa dalam wujud memberikan bantuan alat peraga untuk pengenalan materi penjumlahan dan pengurangan bilangan asli berbahan kayu beserta bimbingan peragaan penggunaan alat peraga kepada para guru di PAUD Terpadu Siti Hajar. Diharapkan kegiatan ini akan membantu guru mengenalkan matematika kepada siswa dan menggunakan alat peraga secara dini dengan benar, sebagai upaya membantu siswa memahami konsep matematika sederhana yaitu membantu memahami konsep abstrak menjadi lebih konkret.
Emotional Context of Newspaper Articles about Covid-19
Authors: Pervukhina Svetlana
Published: June 2024

This paper explores the newspaper texts about Covid-19 from the point of view of emotions. New Zealand has been chosen for the country where Coronovirus pandemic was kept at bay for a long time. But after the cases started to escalate, the situation changed and the tone of newspapers changed, too. The analysis showed the dependence of emotions in the texts and the rise of Covid-19 cases as an indicator of danger. The article analyses three phases of the situation in New Zealand with Covid, such as phase 1 when the number of new cases was controlled, phase 2 when the number of new cases was quickly escalating, and phase 3 when the number of new cases was still high but not so quickly changing. The corpora were analyzed from the point of view of negative and positive reaction to the situation of pandemic escalation in the world and in New Zealand. The findings show a strong relation of the social and textual contexts.
SILENCER-COOLER AS A MEANS OF REDUCING THE EXTERNAL NOISE OF THE "TRITON-01" ARMORED VEHICLE
Authors: Fedorov Volodymyr , Korpach Oleksii , Yashchenko Dmytro , Kolomiets Maksym
Published: June 2024

The problem of camouflage of military equipment is extremely urgent. In this work, a certain improvement of masking properties is proposed by reducing the level of external noise for the Triton-01 armored car. The Triton-01 armored car is equipped with a remote-controlled combat module, a reconnaissance and target detection system, and an information transmission system. This armored car has a number of sources of noise, among which the exhaust system is quite powerful, that is, the noise of exhaust gases. This type of noise is reduced by appropriate mufflers. As practical studies show, at the moment the noise of exhaust gases of military equipment is not sufficiently suppressed by mufflers. We offer a developed complex muffler consisting of two mufflers connected in series: a single-chamber reactive muffler and a cooling muffler. A muffler-cooler of exhaust gas noise has been developed, which contains a hermetic housing filled with refrigerant, inlet and outlet nozzles and a gas pipe for exhaust gases, made straight along the axis of the muffler and with shaped walls that provide the maximum perimeter in a given section. Passing through the gas pipeline, the exhaust gases give off heat to the cooling medium through its walls. The developed one is structurally different from the existing silencers-coolers: the contact area of the cooling liquid with the surface of the silencer is significantly increased. As a result of the cooling of exhaust gases, the speed of movement of the latter is significantly reduced, and as a result, the level of acoustic (noise) vibrations present in these gases. The work calculates the cooling system, which should cool the exhaust gases. A proposal was made to use a refrigerant that is prepared in advance for the combat departure of an armored vehicle. There are possible options for preparing the refrigerant: the armored car itself or a specialized mobile installation.
IMPROVING THE EFFICIENCY OF TRAFFIC LIGHT CONTROL AT ROAD INTERSECTIONS
Authors: Khitrov Ihor , Nykonchuk Viktoriia
Published: June 2024

From the functional point of view, the intersection is the most complex element of the road network. It is here that the traffic flows in different directions cross, and various maneuvers take place. This indicates that the intersection is a place with an increased concentration of conflict situations and an increased risk of traffic accidents. At most high-flow intersections, traffic is controlled by traffic lights, and their inefficient operation can lead to unnecessarily long wait times and overall increase in traffic delays.
The research analyzed a regulated intersection at the crossing of Stepana Bandery and Viacheslava Chornovola main streets in the city of Rivne. This intersection is characterized by constant significant traffic jams.
To simulate traffic conditions at this intersection, the research used PTV Vissim software. Observations of traffic flows, their distribution by directions, and traffic light regulation parameters were used as initial data for modeling the intersection traffic scheme.
The main problem that must be solved when considering isolated traffic light intersections is the calculation and optimization of the signal plan, which involves: determining the number of phases; determining cycle duration; distribution, i.e. determining parts of available green time for each phase; modeling of traffic situations that may arise due to the passage of priority vehicles, congestion of vehicles in intersection areas during peak periods or other situations. At the same time, it is necessary to achieve the best possible characteristics of the intersection functioning.
According to the research results, the road conditions were modeled and the signal plan was optimized with the use of PTV Vissim software. Simulation modeling of the intersection included drawing a road network, installing traffic lights (signal controllers) with a description of their work (choosing the type of light signaling devices, creating signal groups and traffic light signals, parameters for coordinating signals), forming pedestrian zones and a node, performing calculations with subsequent analysis of the received data.
In order to improve the efficiency of the intersection, two options for the operation of the traffic light controllers are offered:
1. Lengthening of the “green” phase, for the convenience of turning to the left (by reducing the phase of oncoming traffic in one direction by 5 seconds). The total duration of the cycle of 70 seconds will not change;
2. Implementation of the third phase – fully pedestrian in all directions, lasting 20 seconds. The total duration of the cycle will increase to 90 seconds.
A more progressive measure can be the introduction of adaptive systems, which are based on new traffic monitoring technologies and allow obtaining accurate data on traffic flows in real time and performing adaptive control of traffic lights, that is, adapting the signal plan in real time to changes in traffic flows.
Fostering student authorship skills in synthetic biology
Authors: Roberts Louis A. , Farny Natalie G.
Published: June 2024

Women and racial minorities are underrepresented in the synthetic biology community. Developing a scholarly identity by engaging in a scientific community through writing and communication is an important component for STEM retention, particularly for underrepresented individuals. Several excellent pedagogical tools have been developed to teach scientific literacy and to measure competency in reading and interpreting scientific literature. However, fewer tools exist to measure learning gains with respect to writing, or that teach the more abstract processes of peer review and scientific publishing, which are essential for developing scholarly identity and publication currency. Here we describe our approach to teaching scientific writing and publishing to undergraduate students within a synthetic biology course. Using gold standard practices in project-based learning, we created a writing project in which students became experts in a specific application area of synthetic biology with relevance to an important global problem or challenge. To measure learning gains associated with our learning outcomes, we adapted and expanded the Student Attitudes, Abilities, and Beliefs (SAAB) concept inventory to include additional questions about the process of scientific writing, authorship, and peer review. Our results suggest the project-based approach was effective in achieving the learning objectives with respect to writing and peer reviewed publication, and resulted in high student satisfaction and student self-reported learning gains. We propose that these educational practices could contribute directly to the development of scientific identity of undergraduate students as synthetic biologists, and will be useful in creating a more diverse synthetic biology research enterprise.
Regulation of the Nrf2/HO-1 axis by mesenchymal stem cells-derived extracellular vesicles: implications for disease treatment
Authors: Su Hua , Wang Zhongan , Zhou Lidan , Liu Dezhi , Zhang Nian
Published: June 2024

This comprehensive review inspects the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) across multiple organ systems. Examining their impact on the integumentary, respiratory, cardiovascular, urinary, and skeletal systems, the study highlights the versatility of MSC-EVs in addressing diverse medical conditions. Key pathways, such as Nrf2/HO-1, consistently emerge as central mediators of their antioxidative and anti-inflammatory effects. From expediting diabetic wound healing to mitigating oxidative stress-induced skin injuries, alleviating acute lung injuries, and even offering solutions for conditions like myocardial infarction and renal ischemia-reperfusion injury, MSC-EVs demonstrate promising therapeutic efficacy. Their adaptability to different administration routes and identifying specific factors opens avenues for innovative regenerative strategies. This review positions MSC-EVs as promising candidates for future clinical applications, providing a comprehensive overview of their potential impact on regenerative medicine.
p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells
Authors: Okamura Daiji , Kohara Aoi , Chigi Yuta , Katayama Tomoka , Sharif Jafar , Wu Jun , Ito-Matsuoka Yumi , Matsui Yasuhisa
Published: June 2024

Mammalian germ cells are derived from primordial germ cells (PGCs) and ensure species continuity through generations. Unlike irreversible committed mature germ cells, migratory PGCs exhibit a latent pluripotency characterized by the ability to derive embryonic germ cells (EGCs) and form teratoma. Here, we show that inhibition of p38 mitogen-activated protein kinase (MAPK) by chemical compounds in mouse migratory PGCs enables derivation of chemically induced Embryonic Germ-like Cells (cEGLCs) that do not require conventional growth factors like LIF and FGF2/Activin-A, and possess unique naïve pluripotent-like characteristics with epiblast features and chimera formation potential. Furthermore, cEGLCs are regulated by a unique PI3K-Akt signaling pathway, distinct from conventional naïve pluripotent stem cells described previously. Consistent with this notion, we show by performing ex vivo analysis that inhibition of p38 MAPK in organ culture supports the survival and proliferation of PGCs and also potentially reprograms PGCs to acquire indefinite proliferative capabilities, marking these cells as putative teratoma-producing cells. These findings highlight the utility of our ex vivo model in mimicking in vivo teratoma formation, thereby providing valuable insights into the cellular mechanisms underlying tumorigenesis. Taken together, our research underscores a key role of p38 MAPK in germ cell development, maintaining proper cell fate by preventing unscheduled pluripotency and teratoma formation with a balance between proliferation and differentiation.
Advances in human glutamine-hydrolyzing synthetases and their therapeutic potential
Authors: Zhu Wen , Nardone Alanya J. , Pearce Lucciano A.
Published: June 2024

Bifunctional enzymes, characterized by their dual active sites, enable efficient chemical conversion and substrate channeling using elegant coupling mechanisms to coordinate the two active sites. In humans, several bifunctional enzymes synthesize de novo carbon-nitrogen bonds by hydrolyzing glutamine and ATP in distinct active sites. Notable examples include guanosine monophosphate synthetase, cytidine triphosphate synthetase, phosphoribosylformyl-glycinamidine synthase, asparagine synthetase, and nicotinamide adenine dinucleotide synthetase. A more complex example of multifunctional glutamine-hydrolyzing synthetases in humans is carbamoyl phosphate synthetase. These enzymes are crucial for the biosynthesis of amino acids, nucleic acids, and co-factors, thereby playing pivotal roles in human health. This review delineates recent progress in understanding the structural characteristics, regulatory mechanisms, and disease relevance of glutamine-hydrolyzing synthetases in humans. Insights into their catalysis and activity regulation offer potential pathways for developing novel therapeutics.
Phosphorescent iridium (III) complex with covalent organic frameworks as scaffolds for highly selective and sensitive detection of homocysteine
Authors: Deng Chuti , Xu Juntong , Zhang Qi , Fan Yong
Published: June 2024

Introduction: Developing a convenient and cost-effective platform for detecting homocysteine (Hcy) is of great interest as Hcy has been found to be a biomarker for Alzheimer’s disease, gastric cancer, and other diseases.

Methods: In this study, we synthesized five phosphorescent Ir(C∧N)2(N∧N)+ compounds (Irn, n = 1–5) with various substituents (-CHO or -CHO/-NH2), which were then doped into a covalent organic framework (COF) host via covalent bonding.

Results and Discussion: The resulting optimal composites (denoted as Ir4/5@EBCOF) with -CHO/-NH2 substituents not only overcame the self-quenching issue of the bare Ir4/5 complexes but also showed rapid, highly selective, and sensitive detection of Hcy, with a limit of detection (LOD) of 0.23 μM and reaction time of 88 s. The sensing mechanism was revealed as the unique cyclization reaction between Ir(III) and Hcy that forms a six-membered ring. During the process, the color changes in the composites can be observed visually. It is expected that these phosphorescent Iridium (III) complexes with COFs will have the potential to serve as promising platforms for detecting thiols.
Synthesis and utility of N-boryl and N-silyl enamines derived from the hydroboration and hydrosilylation of N-heteroarenes and N-conjugated compounds
Authors: Cao Vinh Do , Joung Seewon
Published: June 2024

Catalytic hydroboration and hydrosilylation have emerged as promising strategies for the reduction of unsaturated hydrocarbons and carbonyl compounds, as well as for the dearomatization of N-heteroarenes. Various catalysts have been employed in these processes to achieve the formation of reduced products via distinct reaction pathways and intermediates. Among these intermediates, N-silyl enamines and N-boryl enamines, which are derived from hydrosilylation and hydroboration, are commonly underestimated in this reduction process. Because these versatile intermediates have recently been utilized in situ as nucleophilic reagents or dipolarophiles for the synthesis of diverse molecules, an expeditious review of the synthesis and utilization of N-silyl and N-boryl enamines is crucial. In this review, we comprehensively discuss a wide range of hydrosilylation and hydroboration catalysts used for the synthesis of N-silyl and N-boryl enamines. These catalysts include main-group metals (e.g., Mg and Zn), transition metals (e.g., Rh, Ru, and Ir), earth-abundant metals (e.g., Fe, Co, and Ni), and non-metal catalysts (including P, B, and organocatalysts). Furthermore, we highlight recent research efforts that have leveraged these versatile intermediates for the synthesis of intriguing molecules, offering insights into future directions for these invaluable building blocks.
Discovery of new Schiff bases of the disalicylic acid scaffold as DNA gyrase and topoisomerase IV inhibitors endowed with antibacterial properties
Authors: Al-Wahaibi Lamya H. , Mahmoud Mohamed A. , Alzahrani Hayat Ali , Abou-Zied Hesham A. , Gomaa Hesham A. M. , Youssif Bahaa G. M. , Bräse Stefan , Rabea Safwat M.
Published: June 2024

DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids (5a-k) to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets 5f-k exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound 5h demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060 μg/mL against S. aureus, E. coli, and P. aeruginosa. 5h had a MIC value of 0.050 μg/mL against B. subtilis, which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives 5f, 5h, 5i, and 5k against E. coli DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on E. coli DNA gyrase, with IC50 values ranging from 92 to 112 nM. These results indicate that 5f, 5h, 5i, and 5k are more effective than the reference novobiocin, which had an IC50 value of 170 nM. Compounds 5f, 5h, 5i, and 5k were subjected to additional assessment against E. coli topoisomerase IV. Compounds 5h and 5i, which have the highest efficacy in inhibiting E. coli gyrase, also demonstrated promising effects on topoisomerase IV. Compounds 5h and 5i exhibit IC50 values of 3.50 µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin’s IC50 value of 11 µM. Docking studies demonstrate the potential of compound 5h as an effective dual inhibitor against E. coli DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development.
Synthesis and full-spectrum-responsive photocatalytic activity from UV/Vis to near-infrared region of S-O decorated YMnO3 nanoparticles for photocatalytic degradation of ibuprofen
Authors: Feng Zixia
Published: June 2024

The oxalic acid complexation method and sulfuric acid heat treatment method were used to synthesize the YMnO3 (YMO) and YMO-SO42- (YMO-SO) photocatalysts. The YMO-SO photocatalyst maintained the crystal structure of YMO, but the particle size increased slightly and the optical band gap decreased significantly. The YMO-SO photocatalyst demonstrates a wide range of light absorption capabilities, covering ultraviolet, visible and near-infrared light. The photocatalytic activity of YMO-SO was investigated with ibuprofen as the target pollutant. The YMO-SO photocatalyst exhibits high ultraviolet (UV), visible and near-infrared photocatalytic activity. Experiments with different environmental parameters confirmed that the best catalyst content was 1 g/L, the best drug concentration was 75 mg/L and the best pH value was 7. The capture experiment, free radical detection experiment and photocatalytic mechanism analysis confirmed that the main active species of YMO-SO photocatalyst were hole and superoxide free radical.
Utilization of the Shensheng-Piwen changed medicinal powder extracts combines metal-organic frameworks as an antibacterial agent
Authors: Jin Haiqun , Zhang Xiujun , Ma Xiaoqing , Meng Xin , Lin Zhenguang , Li Xiaoyuan , Hu Guojie , Chen Yao
Published: June 2024

Introduction

Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs.

Methods

This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts.

Results

Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against S. aureus, with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of S. aureus revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of S. aureus. Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect.

Discussion

In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against S. aureus infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.
Impacts of COVID-19 pandemic on culture-proven sepsis in neonates
Authors: Yang Xiaofeng , Ren Luxin , Gong Min , Lu Yanhong , Ding Xin
Published: June 2024

Objective

To assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved.

Methods

This retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children’s hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016–2019) and during the COVID-19 pandemic Phase II (2020–2022).

Results

A total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p < 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p < 0.05) and meningitis (p < 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis.

Conclusion

COVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.
Anti-chlamydial activity of vaginal fluids: new evidence from an in vitro model
Authors: Morselli Sara , Ceccarani Camilla , Djusse Marielle Ezekielle , Laghi Luca , Camboni Tania , Consolandi Clarissa , Foschi Claudio , Severgnini Marco , Marangoni Antonella
Published: June 2024

Introduction

We assessed the in vitro anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract Chlamydia trachomatis viability.

Methods

Forty vaginal samples were collected from a group of reproductive-aged women and their anti-chlamydial activity was evaluated by inhibition experiments. Each sample underwent 16S rRNA metabarcoding sequencing to determine the bacterial composition, as well as 1H-NMR spectroscopy to detect and quantify the presence of vaginal metabolites.

Results

Samples characterized by a high anti-chlamydial activity were enriched in Lactobacillus, especially Lactobacillus crispatus and Lactobacillus iners, while not-active samples exhibited a significant reduction of lactobacilli, along with higher relative abundances of Streptococcus and Olegusella. Lactobacillus gasseri showed an opposite behavior compared to L. crispatus, being more prevalent in not-active vaginal samples. Higher concentrations of several amino acids (i.e., isoleucine, leucine, and aspartate; positively correlated to the abundance of L. crispatus and L. jensenii) lactate, and 4-aminobutyrate were the most significant metabolic fingerprints of highly active samples. Acetate and formate concentrations, on the other hand, were related to the abundances of a group of anaerobic opportunistic bacteria (including Prevotella, Dialister, Olegusella, Peptostreptococcus, Peptoniphilus, Finegoldia and Anaerococcus). Finally, glucose, correlated to Streptococcus, Lachnospira and Alloscardovia genera, emerged as a key molecule of the vaginal environment: indeed, the anti-chlamydial effect of vaginal fluids decreased as glucose concentrations increased.

Discussion

These findings could pave the way for novel strategies in the prevention and treatment of chlamydial urogenital infections, such as lactobacilli probiotic formulations or lactobacilli-derived postbiotics.
Persian compounds in the mental lexicon
Authors: Yousefzadeh Bahareh , Libben Gary , Segalowitz Sidney J.
Published: June 2024

Compound words exhibit properties of both single words and phrases, raising the question of the extent to which compounds are processed as single units or as word combinations. Most studies have addressed this in Germanic languages (English, German and Dutch) which have the similar compound structure of modifier-head ordering. To see whether this limits our understanding of compound word processing and to examine compound decomposition in another language, we presented Persian stimuli auditorily in a paradigm involving typing out stimuli. We examined the effects of semantic transparency, modifier-head ordering and the potential differences between attached compounds written without spaces and those with a space between the constituents. We report the inter-keystroke-interval times, yielding letter-by-letter production of compound structures produced by 31 native speakers of Persian. Results analyzed in a linear mixed-model regression analysis suggested that, for all compounds, typing speed is slowed at the boundary between the constituents of Persian compound words. These effects, which we interpret to be evidence of morphological decomposition, were present for both semantically transparent and opaque compounds, for both head-initial and head-final compounds, and for both attached and spaced compounds. We observed greater morphological decomposition effects in semantically transparent (versus opaque) compounds. We also observed that the way transparency influences the degree of decomposition is moderated by headedness. Thus, this first report for the written production of compound words confirms previous observations of significant decomposition at morphological boundaries in English compounds, but with variation specific to Persian.
Efficacy and safety evaluation of Allisartan Isoproxil in patients with hypertension: a meta-analysis
Authors: Zhao Fengfeng , Liu Yihua , Chen Liang
Published: June 2024

Objective

This study aimed to evaluate the effectiveness and safety of Allisartan Isoproxil in the management of hypertension.

Methods

A comprehensive search was conducted across both English and Chinese databases, including the Cochrane Library, Embase, PubMed, Web of Science, Chinese Journal Full Text Database (CNKI), Wanfang Digital Periodical Full Text Database, and VIP Chinese Periodical Database (VIP), up to March 24, 2024. Randomized controlled trials (RCTs) investigating alisartan axetil for hypertension management were selected. Literature quality was assessed, and data were extracted for meta-analysis using Stata 15.1 software. The quality of evidence for outcome indicators was evaluated using the GRADE system level.

Results

Six RCTs involving 767 participants were included. Meta-analysis revealed that, compared to placebo, the Allisartan Isoproxil group exhibited a significant reduction in systolic blood pressure (SBP) [WMD = −8.08, 95% CI (−11.81, 4.10), p = 0.000] and brachial-ankle pulse wave velocity (baPWV) [SMD = −0.69, 95% CI (−1.17, 0.20), p = 0.006]. However, the reduction in diastolic blood pressure (DBP) was not statistically significant [WMD = −5.48, 95% CI (−11.07, 0.10), p = 0.054]. Additionally, compared to calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB), Allisartan Isoproxil did not significantly affect SBP [WMD = 0.20, 95% CI (−3.71, 4.10), p = 0.921] or DBP [WMD = 0.16, 95% CI (−2.11, 2.43), p = 0.891]. Allisartan Isoproxil demonstrated superior effects in increasing nitric oxide (NO) levels and decreasing endothelin (ET) levels compared to control groups [WMD = 9.56, 95% CI (6.42, 12.71), p = 0.000], [WMD = −7.42, 95% CI (−11.13, −3.71), p = 0.000], and showed a higher effective control rate of blood pressure [RR = 1.26, 95% CI (1.13, 1.41), p = 0.000]. Subgroup analysis did not reveal significant differences. Regarding safety, there were no statistically significant differences in adverse events between the Allisartan Isoproxil group and the control groups [RR = 0.99, 95% CI (0.74, 1.32), p = 0.928], and no fatal adverse events were reported.

Conclusion

Allisartan Isoproxil is effective in reducing SBP and baPWV, increasing NO, decreasing ET, and achieving a higher control rate of blood pressure in patients with essential hypertension. These benefits are achieved with minimal adverse reactions.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023467869, identifier PROSPERO CRD42023467869.
Exploring the causal relationship between immune cell and all-cause heart failure: a Mendelian randomization study
Authors: Li Jixu , Liu Liangliang , Luo Qiuyan , Zhou Weiyue , Zhu Yao , Jiang Weimin
Published: June 2024

Background and objectives

Heart failure (HF) is a disease with numerous genetic and environmental factors that affect it. The results of previous studies indicated that immune phenotypes are associated with HF, but there have been inconclusive studies regarding a causal relationship. Therefore, Mendelian randomization (MR) analyses were undertaken to confirm the causal connections between immune phenotypes and HF, providing genetic evidence supporting the association of immune cell factors with HF risk.

Methods

We selected instrumental variables that met the criteria based on data from the results of genome-wide association studies (GWAS) of immune phenotype and all-cause HF. An evaluation of the causal association between 731 immune cell factors and HF risk was carried out using the inverse variance weighted (IVW), MR-Egger regression (MR-Egger), and weighted median (WM) analysis methods. To determine the horizontal pleiotropy, heterogeneity, and stability of the genetic variants, the MR-Egger intercept test, Cochran's Q test, MR-PRESSO, and leave-one-out sensitivity analysis were performed.

Results

MR principal method (IVW) analysis showed that a total of 38 immune cell-related factors were significantly causally associated with HF. Further analyses combining three methods (IVW, MR-Egger and WME) showed that six exposure factors significantly associated with heart failure, as shown below. The effect of Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell on heart failure was positive. Whereas, a reverse effect was observed for CD14+ CD16+ monocyte% monocyte.

Conclusion

We investigated the causal relationship between immune phenotypes and all-cause HF. According to the results, Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell Absolute Count, CD62l- CD86+ myeloid Dendritic cell% Dendritic cell, CD39+ CD8+ T cell% CD8+ T cell, CD3 on Central Memory CD4+ T cell aggravate HF, and the risk of HF is decreased by CD14+ CD16+ monocyte% monocyte. These phenotypes may serve as new biomarkers, providing new therapeutic insights for the prevention and treatment of all-cause HF.