bluuebunny/crossref_metadata_2025 huggingface dataset:
NATURAL ATTRACTIONS AND E-WOM: DRIVERS OF DESTINATION LOVE IN INDONESIAN CAMPERVAN TOURISM
Authors: Nuh Ahmad , Rizan Mohamad , Muhammad Sadat Andi
Published: January 2025

The given study aims to explore the impact of natural attraction, electronic word-of-mouth (e-WOM), and satisfaction on destination love within the context of campervan tourism in Indonesia. The research utilized a sample of 483 respondents from Jakarta and other cities in Indonesia and employed structural equation modeling (SEM) using partial least squares (PLS) to test eight hypotheses. The findings indicate that natural attraction, e-WOM, and satisfaction have a significant positive effect on destination love. Specifically, natural attraction has a strong positive influence on destination love, satisfaction has a weak positive effect on destination love, and e-WOM has a strong positive effect on both destination love and satisfaction. The study conducted a multi-group analysis and found no significant difference between male and female respondents in their perspectives on the eight hypotheses. The implications of lovemarks theory suggest that brands should concentrate on establishing strong emotional connections with consumers to foster loyalty beyond reason.
Pemasangan Pompa Air Listrik Pada Masjid Salim RW.02 Desa Mulyoagung Kabupaten Malang
Authors: Sutjipto Rachmat , Setiawan Awan , Syamsuri Tresna Umar , Kurniawan Bakti Indra , Dhesah Kharisma Dhimas , Nurhadi Slamet
Published: January 2025

Ketersediaan air bersih adalah salah satu kebutuhan yang sangat vital untuk masjid. Air bersih ini umumnya diambil dari sumur menggunakan pompa air tenaga listrik. Penggunaan pompa air ini pada umumnya ada umur pakai. Yang terjadi pada masjid Salim sering mengalami kerusakan, di servis kembali bisa, kemudian setelah digunakan beberapa waktu rusak kembali. Hal ini sangat mengganggu untuk aktifitas masjid yang memerlukan kontinuitas air bersih terus menerus. Untuk mengatasi masalah ini, maka dilakukan penggantian pompa air listrik dengan yang baru. Otomasi pompa air dirancang menggunakan sakelar apung yang dipasang dalam tangki air. Pompa ini juga dirancang sistem langsung, ketika kran air dihidupkan pompa langsung menyala. Untuk tandon air masih menggunakan yang lama karena kondisi masih memadai. Hasil pengujian di lapangan menunjukan bahwa pompa air otomatis dan langsung yang diusulkan dalam program pengabdian ini telah bekerja dengan baik sesuai dengan perencanaan.
BIMBINGAN DAN PENYULUHAN TENTANG PENTINGNYA MEMBANGUN LOYALITAS PELANGGAN PADA KELOMPOK USAHA JAMAAH MASJID AL IKHLAS RT.07, RW.17, SUDIMORO,MOJOLANGU KEC.LOWOKWARU KOTA MALANG
Authors: Samboro Joko , Maskan M , Utomo Heru , Helmy Abdullah , Afandi Yosi , Hadi Musthofa
Published: January 2025

The purpose of this PKM is to find the problems faced by the congregation of the AL Ikhlas Mosque RT.076 RW.17 Sudimoro, Mojolangu Village, Lowokwaru District, Malang City and at the same time provide the right solution to achieve increased knowledge and skills in the field of marketing management, especially building customer loyalty. The methods used are: observation, to observe activities carried out both in the economic and socio-religious fields, then interviews, explored to find problems and solutions that will be offered and simulations, to find the most appropriate alternatives to market goods more effectively. Description of the technology to be applied. 1. In the form of lectures: Study Group participants are gathered in a certain room and given a lecture on devotion material in the form of: Customer Loyalty. 2. Guidance and Training: In the form of practical guidance and training and discussion of experiences and obstacles in the field. 3. Simulation practice: In the form of a demonstration of how entrepreneurs offer goods, and how to attract potential consumers, until loyal customers are formed
 
Keywords: guidance and counseling, customer loyalty.
Implementasi Infrastruktur Jaringan Untuk Mendukung Program Sertifikasi SMA Islam Kepanjen Kabupaten Malang
Authors: Ariyanto Yuri , Syaifudin Yan Watequlis , Harijanto Budi , Puspitasari Dwi , Setiadi Chandrasena , Astiningrum Mungki
Published: January 2025

The Community Service Program intends to support the Empowering School Certification Program by establishing computer network infrastructure at the Islamic High School in Malang's Kepanjen region.  According to analysis studies, the current network falls short of the online access criteria for certification tests. This intervention employed two essential approaches. The first option entails installing standard-based computer networks in the school laboratory facilities. The second option gives information technology (IT) educators extensive network management support. The Community Service Program Team of the State Polytechnic of Malang runs the initiative, which focuses on creating a reliable network topology and increasing the skills of the school's IT staff. This intervention is expected to increase overall educational quality and develop network infrastructure that will allow certification programs to be implemented. The accompanying seeks to provide expertise to Kepanjen's Islamic High School Team so that they can manage the network more independently. This community service project is designed to optimize the digital learning ecosystem, improve education and evaluation processes, and prepare students for the complexities of the digital age. This will be accomplished through collaboration between the Community Service Program team and the Islamic High School of Kepanjen District Malang.
PENDAMPINGAN INTERNET MARKETING DALAM MENDUKUNG KEGIATAN PROMOSI PADA UMKM JASMINE COLLECTION KEL. TANJUNG REJO KEC. SUKUN KOTA MALANG
Authors: Utomo Heru , Maskan Mohammad , Samboro Joko , Khabibah Umi , Indrianti Titien , Sudjanarti Dwi
Published: January 2025

competitiveness in order to survive, continue to run and even be able to develop. For this purpose, one strategy that can be done in managing their business is to apply internet-based information technology as a support in various processes of their business activities.  Internet marketing is a marketing activity with the application of information technology, which includes activities to promote products and/or services through the internet. Jasmine Collection Kel. Tanjung Rejo, Sukun District, Malang City, one of the newly developing MSMEs, has not been optimal in implementing online marketing which is part of Internet marketing. Online marketing has been carried out through private Whatsapp and Instagram statuses. This PKM activity aims to help Jasmine Collection MSMEs maximize online marketing activities. The results of this activity are in the form of logos, ebooklets, ebrochures, and videos that will be uploaded to the MSME Instagram, and the website with the address https://jasminedaster2023.blogspot.com/
PENGGUNAAN SOCIAL COMMERCE SEBAGAI MEDIA UNTUK MENINGKATKAN PENJUALAN PRODUK UMKM DAN PERHITUNGAN BIAYA PEMASARANNYA DI DESA WISATA BUDAYA TULUSBESAR KECAMATAN TUMPANG
Authors: Ernawati Widi , Afandi Aang , Oktavia Fathimatus , Haris Zainal , Maula Farisa , Sari Padma
Published: January 2025

Desa Tulusbesar merupakan desa yang terletak di wilayah Kabupaten Malang. Potensi yang terdapat pada desa ini sangat besar terutama dalam bidang seni dan budaya. Terdapat banyak pagelaran seperti bantengan, jaranan, wayangan dan ada juga pelaku UMKM yang memproduksi topeng malangan, kuda lumping, wayang, lampu hias dan masih banyak lagi. Salah satu indikator kesuksesan pelaku UMKM Desa Wisata Budaya Tulusbesar adalah kesejahteraan masyarakat Desa Tulusbesar yang meningkat. Hal tersebut dapat diwujudkan dengan cara meningkatkan penjualan produk dari hasil keterampilan masyarakat desa ini. Tantangan dan permasalahan yang terjadi pada lingkungan bisnis saat ini adalah masyarakat banyak melakukan transaksi jual beli melalui platform digital, sehingga dibutuhkan pengetahuan dan keterampilan khusus untuk bisa memasarkan berbagi macam produk melalui metode tersebut. Agar usaha yang dimiliki masyarakat Desa Wisata Busaya Tulusbesar ini bisa bertahan dan lebih berkembang, maka tim PPM memberikan pelatihan penggunaan social commerce untuk meningkatkan penjualan UMKM di Desa Wisata Busaya Tulusbesar serta perhitungan biaya pemasarannya.
PENGENALAN MICROSOFT OFFICE DI TK DHARMA WANITA TUNGLUR BADAS KABUPATEN KEDIRI
Authors: Sumarno Agus Sukoco Heru , Mandayatma Eka , Saukani Imam , Radianto Donny , Pracoyo Agus , Azhar Gilang Al
Published: January 2025

Integrated Primary Education (TK Dharma Wanita) is a basic educational activity  organized by and with the help of primary education officers. So, TK Dharma Wanita is a community initiative in the field of basic education, in which the village head is the responsible party. AA Gde Muninjaya (2002:169) states:“Basic education services are a form of integrated basic education services provided in primary education. Nowadays, computers are the tools used to process and create work reports, whether in the form of Word, Excel or PowerPoint data. Up to now, TK Dharma Wanita, headquartered in  Sumberejo Badas Pare Village, Kediri Regency, still uses a conventional manual typewriter for reporting, which leads to many limitations that TK faces in terms of administrative operations. and data management.
ONLINE AND OFFLINE MARKETING MENTORING AND TRAINING FOR SMEs IN JOYOGRAND MERJOSARI MALANG
Authors: Umi Umi Khabibah , Herijanto Pudji , Nurtjahjani Fullchis , Nurdjizah Nurdjizah , Aini Lilies Nur
Published: January 2025

Assistance and training for SMEs in RW 8 Joyogrand Merjosari Malang Housing is a collaboration with the world of education. This is because there is a need for knowledge about marketing, both online through social media and offline through tools in the form of product catalogs. The catalog displays all the products produced, along with their prices, so this will really help potential consumers in recognizing and knowing what products are produced. The final thing that is hoped for is that a buying and selling transaction will occur between them. If you understand the meaning of promotion, you will know the true purpose of promotion. Not just communication to attract interest or introductions. The aim of promotion is to generate sales from capturing the market, as well as increasing the number of sales, increasing awareness of the sustainability of the buying and selling relationship. The training program for presenting promotional ideas on Facebook/Instagram and the Product Catalog is one of the training programs that can help disseminate product information. Likewise for UKMs in RW 08. They need to open themselves to other people regarding what they produce. By being known by other people, it will increase sales
PELATIHAN PENGELOLAAN DAYA TARIK WISATA ALAM SUMBERINGIN DI DESA WRINGINSONGO, KECAMATAN TUMPANG
Authors: Safitri Isnaini Nur , Amanda Tiara Estu , Betari Asa Wisesa , Setiawan Ardian Wahyu , Hoesny Mariana Ulfah
Published: January 2025

This community service is aimed at accommodating the needs of the management of the Sumberingin natural tourist attraction in improving the ability to manage natural tourist attractions and tourism potential in the Wringinsongo village area by involving tourism business actors (travel agents) to increase tourist visits, both local and foreign. Participants in this training are tourist attraction managers, especially Sumberingin tourist attraction managers and Wringinsongo village managers, Tumpang District, Malang Regency. This activity is expected to improve the quality of human resources for tourist attraction managers by increasing the ability to manage tourist attractions, which will then be implemented as an effort to increase local and foreign tourist visits. This activity was carried out in some stages, namely planning (to find out the number of participants who were involved and the materials needed for the training), coordination with the related parties (representative of partner village members, travel agent, and tour guide) to ensure the plans made are in accordance with the needs, preparation of Focused Group Discussion (FGD) materials, survey to the exact location in the partner village to ensure the prepared materials are suitable with the condition of the village, doing FGD with the, and evaluation which is giving questionnaires to the participants regarding the implementation and materials.
PELATIHAN KEWIRAUSAHAAN MELALUI DIVERSIFIKASI SAYUR MAYUR BERUPA ICE CREAM BAGI WARGA DESA DUWET KEC. TUMPANG KAB.MALANG
Authors: Wahyu Ellyn Eka , Oktora Yekie Senja
Published: January 2025

The agricultural and plantation potential produced by Duwet Village includes vegetables. Several types of vegetables produced include mustard greens and tomatoes. These two types of vegetables have great potential to develop their production, not only as complementary vegetables to food dishes consumed daily by families; However, it can be developed into a food product that is more varied and has more selling value, is popular, attractive but still healthy. The problem is that mustard greens and tomatoes still receive very little processing attention so that their selling value can be increased. The existing mustard greens and tomatoes are generally only for sale and/or processed for daily food needs without any other processing alternatives due to the limited knowledge of residents to manage these mustard greens and tomatoes so that they become a product that has product value and selling value. higher. This PPM activity seeks to provide understanding through entrepreneurship training by diversifying mustard greens and tomatoes into ice cream. From this Community Service (PPM) activity, it is hoped that synergy will be created between the residents of Duwet Village, Kec. Overlapping District. Malang with the Malang State Polytechnic, to be able to help partners increase their knowledge so they can produce/process mustard greens and tomatoes as one of the superior products and sell products with a higher selling value and can help the local economy continuously.
Active solar and wind energy potential of urban morphologies on building facades and non-built-up space in between: a case study in Addis Ababa, a Sub-Saharan Africa city
Authors: Debebe Wondwosen , Assefa Tibebu
Published: January 2025

This article explores into the relationship between urban morphology and renewable energy, specifically focusing on the potential for active solar and wind energy in building facades and non-built-up spaces within blocks in Addis Ababa, a typical Sub-Saharan Africa city. The study involved the analysis of eleven urban blocks representing four different urban morphology typologies selected with geospatial clustering. Solar and wind data are obtained from satellite-based and meteorological sources. Wind and solar analyses are conducted using computational fluid dynamics through Ansys Fluent and Rhino Grasshopper in Ladybug, respectively, with the support of ArcGIS. The findings reveal that the changes in the values of some morphological descriptors have inverse relationship when comparing solar and wind potential on building facades. Conversely, changes in the values of other morphological descriptors generally show a direct relationship independently on solar and wind potential on the non-built up space. It is recommended that the combined effects of solar and wind potential on urban facades be considered based on morphological descriptors. Similarly, the independent effects of solar and wind potential on non-built-up spaces should also be recommended according to these descriptors.
Machine learning and molecular dynamics simulations predict potential TGR5 agonists for type 2 diabetes treatment
Authors: Enejoh Ojochenemi A. , Okonkwo Chinelo H. , Nortey Hector , Kemiki Olalekan A. , Moses Ainembabazi , Mbaoji Florence N. , Yusuf Abdulrazak S. , Awe Olaitan I.
Published: January 2025

Introduction

Treatment of type 2 diabetes (T2D) remains a significant challenge because of its multifactorial nature and complex metabolic pathways. There is growing interest in finding new therapeutic targets that could lead to safer and more effective treatment options. Takeda G protein-coupled receptor 5 (TGR5) is a promising antidiabetic target that plays a key role in metabolic regulation, especially in glucose homeostasis and energy expenditure. TGR5 agonists are attractive candidates for T2D therapy because of their ability to improve glycemic control. This study used machine learning-based models (ML), molecular docking (MD), and molecular dynamics simulations (MDS) to explore novel small molecules as potential TGR5 agonists.

Methods

Bioactivity data for known TGR5 agonists were obtained from the ChEMBL database. The dataset was cleaned and molecular descriptors based on Lipinski’s rule of five were selected as input features for the ML model, which was built using the Random Forest algorithm. The optimized ML model was used to screen the COCONUT database and predict potential TGR5 agonists based on their molecular features. 6,656 compounds predicted from the COCONUT database were docked within the active site of TGR5 to calculate their binding energies. The four top-scoring compounds with the lowest binding energies were selected and their activities were compared to those of the co-crystallized ligand. A 100 ns MDS was used to assess the binding stability of the compounds to TGR5.

Results

Molecular docking results showed that the lead compounds had a stronger affinity for TGR5 than the cocrystallized ligand. MDS revealed that the lead compounds were stable within the TGR5 binding pocket.

Discussion

The combination of ML, MD, and MDS provides a powerful approach for predicting new TGR5 agonists that can be optimised for T2D treatment.
Building an open-source community to enhance autonomic nervous system signal analysis: DBDP-autonomic
Authors: Dunn Jessilyn , Mishra Varun , Shandhi Md Mobashir Hasan , Jeong Hayoung , Yamane Natasha , Watanabe Yuna , Chen Bill , Goodwin Matthew S.
Published: January 2025

Smartphones and wearable sensors offer an unprecedented ability to collect peripheral psychophysiological signals across diverse timescales, settings, populations, and modalities. However, open-source software development has yet to keep pace with rapid advancements in hardware technology and availability, creating an analytical barrier that limits the scientific usefulness of acquired data. We propose a community-driven, open-source peripheral psychophysiological signal pre-processing and analysis software framework that could advance biobehavioral health by enabling more robust, transparent, and reproducible inferences involving autonomic nervous system data.
An integrated approach to flood risk assessment using multi-criteria decision analysis and geographic information system. A case study from a flood-prone region of Pakistan
Authors: Ibrahim Muhammad , Huo Aidi , Ullah Waheed , Ullah Safi , Xuantao Zhao
Published: January 2025

Flood risk assessment is crucial for effective disaster risk management and community resilience. However, the current research lacks strength in identifying high-risk areas, implementing flood early warning systems, prioritising risk reduction measures, and allocating resources for emergency response planning and management. This study aims to assess flood hazard in Mirzadhare, Charsadda a highly flood-prone area in Khyber Pakhtunkhwa province of Pakistan. The study used an integrated approach by employing geographical information system (GIS) and multi-criteria decision analysis (MCDA) techniques. Further, the study used multiple datasets, including rainfall, stream density, and village points to map out flood susceptibility in the study region. Data was collected from field surveys, questionnaires, and interviews, allowing for a detailed analysis of flood hazards. Selecting average precipitation, peak river flow, and historical flood frequency as indicators, the weights of the three are 0.4, 0.3, and 0.3 respectively, an indicator system for predicting flood disasters was constructed. The results categorised the study area into four hazard zones: very high, high, medium, and low, based on their susceptibility to flood hazards. The study findings reveal that more than 65% of the area, including agricultural land with other livelihood settlements, is at a very high risk of flood hazard. Over 50% of the population lives in floodplains and faces an extremely high risk of future flood events. The precision of the results may have been affected by the accuracy and completeness of the data sources utilised, such as historical flood records, precipitation data, stream network data, and stream density. This combination of methods enabled the creation of accurate, data-driven flood risk maps. The hazard map of the area serves as a valuable tool for decision-making, resource allocation, and the development of flood risk management strategies. Based on the study findings, regular updates and continuous monitoring are recommended to ensure the accuracy and relevance of the flood hazard information over time.
Communication, inclusion, and environmental justice - journalists’ attitudes towards low-carbon city transformation in China
Authors: Wu Yan , Martens Pim , Krafft Thomas
Published: January 2025

Cities are recognized as significant contributors to carbon emissions due to their numerous productive enterprises and dense populations. Tackling climate change and achieving the transformation to low-carbon cities requires public participation. News media serve as the primary channel for the public to gain relevant information, and journalists’ attitudes significantly influence the content of related news reports. This study focuses on the attitudes of Chinese journalists towards the transition to low-carbon cities, using semi-structured interviews in qualitative research to conduct 31 interviews with participants from Chinese mainstream medias. This research discussed the journalists’ attitudes towards the low-carbon city transition, based on our samples studies, we find that (1) low-carbon city development brings some new opportunities for economic development and improving the overall urban living environment, despite challenges like lack of professional knowledge and information gaps. (2) Newsworthiness, audience preferences, journalists’ climate scientific knowledge, and management mechanisms, are key factors influencing journalists’ choice to cover low-carbon topics. Despite an increase in related reports, many media do not prioritize climate change or low-carbon transitions as core topics, and environmental news have a life cycle. (3) We suggests that media enhance collaboration with stakeholders, increase audience interaction to learn diverse voices, using storytelling and integrating technological innovations to improve low-carbon communication. This study highlights the complex interactions between media, public participation, and environmental policies, offering a holistic view of the challenges and opportunities in promoting more inclusive and equitable low-carbon city transition.
Single-cell RNA sequencing elucidates cellular plasticity in esophageal small cell carcinoma following chemotherapy treatment
Authors: Zhang Qinkai , Gao Ziyu , Qiu Ru , Cao Jizhao , Zhang Chunxiao , Qin Wei , Yang Meiling , Wang Xinyue , Yang Ciqiu , Li Jie , Yang Dongyang
Published: January 2025

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressively progressing malignancy that presents considerable clinical challenges.Although chemotherapy can effectively manage symptoms during the earlystages of SCCE, its long-term effectiveness is notably limited, with theunderlying mechanisms remaining largely undefined. In this study, weemployed single-cell RNA sequencing (scRNA-seq) to analyze SCCE samplesfrom a single patient both before and after chemotherapy treatment. Our analysisrevealed significant cellular plasticity and alterations in the tumormicroenvironment’s cellular composition. Notably, we observed an increase intumor cell diversity coupled with reductions in T cells, B cells, and myeloid-likecells. The pre-treatment samples predominantly featured carcinoma cells in amiddle transitional state, while post-treatment samples exhibited an expandedpresence of cells in terminal, initial-to-terminal (IniTerm), and universally alteredstates. Further analysis highlighted dynamic interactions between tumor cells andimmune cells, with significant changes detected in key signaling pathways, suchas TIGIT-PVR and MDK-SDC4. This study elucidates the complex dynamics of cellplasticity in SCCE following chemotherapy, providing new insights and identifyingpotential therapeutic targets to enhance treatment efficacy.
A family with normal sperm motility carrying a sY86 deletion in AZFa region and partial deletion in AZFc region
Authors: Zhao Yuhong , Zhi Weiwei , Xiong Dongsheng , Li Ningjing , Du Xinrong , Zeng Jiuzhi , Zhang Guohui , Liu Weixin
Published: January 2025

Introduction

Usually, patients with sY84 or sY86 deficiency present with azoospermia, but recent studies have shown that some males with partial AZFa deletions, including sY84 or sY86, exhibit normal fertility. Here, we reported a rare case of AZF deletion in a family, where both father and son exhibited a deletion at the sY86 site in the AZFa region and a partial deletion in the AZFc region.

Methods and Results

Detection was performed using classical multiplex polymerase chain reaction and the “Male AZF Full-region Detection” Panel, revealing specific deletions in AZFa: Yq11.21 (14,607,372–14,637,973), 30.6 kb; AZFc: Yq11.223–11.23 (25,848,831–27,120,665), 1.3 M for the father; and Yq11.223–11.23 (25,505,378–27,120,665), 1.6 M for the son. Notably, although the son’s sperm motility parameters showed no significant abnormalities, there was a history of failed pregnancies for twice, with sperm exhibiting a high rate of head defect.

Discussion

Given the complexities of the reproductive phenotype following AZF region deletions, additional extended genetic testing is necessary when partial deletions in the AZF region are detected, thus providing more accurate predictions of the spermatogenesis in patient. This study provides valuable insights and guidance for clinical decision-making and the implementation of assisted reproductive technologies in such cases.
CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity
Authors: Kong Yaojie , Li Jingyao , Zhao Xueyao , Wu Yanwei , Chen Liang
Published: January 2025

Chimeric Antigen Receptor (CAR)-T cell therapy has rapidly emerged as a groundbreaking approach in cancer treatment, particularly for hematologic malignancies. However, the application of CAR-T cell therapy in solid tumors remains challenging. This review summarized the development of CAR-T technologies, emphasized the challenges and solutions in CAR-T cell therapy for solid tumors. Also, key innovations were discussed including specialized CAR-T, combination therapies and the novel use of CAR-Treg, CAR-NK and CAR-M cells. Besides, CAR-based cell therapy have extended its reach beyond oncology to autoimmune disorders. We reviewed preclinical experiments and clinical trials involving CAR-T, Car-Treg and CAAR-T cell therapies in various autoimmune diseases. By highlighting these cutting-edge developments, this review underscores the transformative potential of CAR technologies in clinical practice.
The role of the C5a-C5aR pathway in iron metabolism and gastric cancer progression
Authors: Ni Qinxue , Yang Hong , Rao Hang , Zhang Liyong , Xiong Mengyuan , Han Xiao , Deng Boshao , Wang Lulu , Chen Jian , Shi Yan
Published: January 2025

Gastric cancer continues to be a leading global health concern, with current therapeutic approaches requiring significant improvement. While the disruption of iron metabolism in the advancement of gastric cancer has been well-documented, the underlying regulatory mechanisms remain largely unexplored. Additionally, the complement C5a-C5aR pathway has been identified as a crucial factor in gastric cancer development. The impact of the complement system on iron metabolism and its role in gastric cancer progression is an area warranting further investigation. Our research demonstrates that the C5a-C5aR pathway promotes gastric cancer progression by enhancing iron acquisition in tumor cells through two mechanisms. First, it drives macrophage polarization toward the M2 phenotype, which has a strong iron-release capability. Second, it increases the expression of LCN2, a high-affinity iron-binding protein critical for iron export from tumor-associated macrophages, by activating endoplasmic reticulum stress in these cells. Both mechanisms facilitate the transfer of iron from macrophages to cancer cells, thereby promoting tumor cell proliferation. This study aims to elucidate the connection between the complement C5a-C5aR pathway and iron metabolism within the tumor microenvironment. Our data suggest a pivotal role of the C5a-C5aR pathway in tumor iron management, indicating that targeting its regulatory mechanisms may pave the way for future iron-targeted therapeutic approaches in cancer treatment.
Squamate reptiles may have compensated for the lack of γδTCR with a duplication of the TRB locus
Authors: Sampson Jordan M. , Morrissey Kimberly A. , Mikolajova Kieran J. , Zimmerly Kourtney M. , Gemmell Neil J. , Gardner Michael G. , Bertozzi Terry , Miller Robert D.
Published: January 2025

Squamate reptiles are amongst the most successful terrestrial vertebrate lineages, with over 10,000 species across a broad range of ecosystems. Despite their success, squamates are also amongst the least studied lineages immunologically. Recently, a universal lack of γδ T cells in squamates due to deletions of the genes encoding the T cell receptor (TCR) γ and δ chains was discovered. Here, we begin to address how the loss of γδ T cells may have impacted the evolution of the squamate immune system. Using the skink Tiliqua rugosa, we found that squamates have not significantly increased the complexity of conventional T cell receptor beta (TCRβ or TRB) chain V regions compared to that of the nearest living squamate relative, the tuatara, Sphenodon punctatus or other amniotes. Our analyses include a putative new TCR locus. This novel locus contains V, D, and J gene segments that undergo V(D)J recombination, albeit with a limited number of gene segments in most squamate species. Based on conserved residues, the predicted protein chain would be expected to form a heterodimer with TCRα. This new TCR locus appears to be derived from an ancient duplication of the TRB locus and is homologous to the recently described T cell receptor epsilon (TRE). TRE is absent from the genomes of the tuatara and all Archosaurs examined and appears squamate specific.
Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo
Authors: Li Xuezhen , Huang Han , Li Yanan , Feng Yi , Wang Jinxuan , Luo Shuping , Chen Yaping , Zhang Yuqin , Yan Guohong , Nan Lihong
Published: January 2025

Object

Neuroinflammation mediated by microglia has emerged as a critical factor in ischemic stroke and neuronal damage. Gualou Guizhi Granule (GLGZG) has been shown to suppress inflammation in lipopolysaccharide (LPS)-activated microglia, though the underlying mechanisms and its protective effects against neuronal apoptosis remain unclear. This study aims to investigate how GLGZG regulates the Notch signaling pathway in microglia to reduce neuroinflammation and protect neurons from apoptosis.

Method

Using in vitro and in vivo models, we explored GLGZG's impact on microglia activation, pro-inflammatory cytokines, and neuronal apoptosis. Microglial cells were activated with LPS, and primary neuronal cells were exposed to LPS-activated microglia to simulate neuroinflammation. Additionally, we investigated the effects of GLGZG in combination with N-[N-[3,5-difluorophenacetyl]-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or siRNA-Notch1 to further elucidate the involvement of the Notch signaling pathway.

Results

GLGZG significantly inhibited microglia activation and reduced neuroinflammation by de-creasing the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in both in vitro and in vivo models. GLGZG also effectively protected against microglia-induced neuronal apoptosis. Mechanistically, GLGZG down-regulated key components of the Notch signaling pathway, in-cluding Notch-1, NICD, RBPSUH, and Hes-1, in activated microglia. Combined treatment with GLGZG and DAPT or siRNA-Notch1 demonstrated enhanced inhibition of microglial activation and neuroinflammation.

Conclusion

Our findings reveal that GLGZG exerts its protective effects through the suppression of the Notch signaling pathway, thereby inhibiting microglia activation, reducing neuroinflammation, and safeguarding neurons from neuroinflammation-induced damage, offering potential as a therapeutic agent for ischemic stroke-induced neuroinflammation.
Unveiling the nanoworld of antimicrobial resistance: integrating nature and nanotechnology
Authors: Sharma Devesh , Gautam Sakshi , Singh Sakshi , Srivastava Nalini , Khan Abdul Mabood , Bisht Deepa
Published: January 2025

A significant global health crisis is predicted to emerge due to antimicrobial resistance by 2050, with an estimated 10 million deaths annually. Increasing antibiotic resistance necessitates continuous therapeutic innovation as conventional antibiotic treatments become increasingly ineffective. The naturally occurring antibacterial, antifungal, and antiviral compounds offer a viable alternative to synthetic antibiotics. This review presents bacterial resistance mechanisms, nanocarriers for drug delivery, and plant-based compounds for nanoformulations, particularly nanoantibiotics (nAbts). Green synthesis of nanoparticles has emerged as a revolutionary approach, as it enhances the effectiveness, specificity, and transport of encapsulated antimicrobials. In addition to minimizing systemic side effects, these nanocarriers can maximize therapeutic impact by delivering the antimicrobials directly to the infection site. Furthermore, combining two or more antibiotics within these nanoparticles often exhibits synergistic effects, enhancing the effectiveness against drug-resistant bacteria. Antimicrobial agents are routinely obtained from secondary metabolites of plants, including essential oils, phenols, polyphenols, alkaloids, and others. Integrating plant-based antibacterial agents and conventional antibiotics, assisted by suitable nanocarriers for codelivery, is a potential solution for addressing bacterial resistance. In addition to increasing their effectiveness and boosting the immune system, this synergistic approach provides a safer and more effective method of tackling future bacterial infections.
Pyrrocidines A and B demonstrate synergistic inhibition of Fusarium verticillioides growth
Authors: Lofton Lily W. , Read Quentin D. , Hamilton Hailey L. , Glenn Anthony E. , Hawkins Jaci A. , Mitchell Trevor R. , Gold Scott E.
Published: January 2025

Fusarium verticillioides—a mycotoxigenic fungus and food safety threat—coinhabits maize kernels with Sarocladium zeae. This protective endophyte produces secondary metabolites of interest, pyrrocidines A and B, which inhibit the growth of F. verticillioides and specifically block fumonisin biosynthesis. Previous transcriptomic analyses found FvZBD1 (FVEG_00314), a gene adjacent to the fumonisin biosynthetic gene cluster, to be induced over 4,000-fold in response to pyrrocidine challenge. Deletion of FvZBD1 resulted in dramatic increases in fumonisin production (FB1 >30-fold). Here, using pyrrocidine dose-response assays, we discovered a potent synergy between pyrrocidines A and B, where they functioned powerfully together to inhibit F. verticillioides growth. Further, results provided evidence that FvZBD1 confers partial tolerance to pyrrocidines, particularly pyrrocidine A, and that pyrrocidine functions through FvZBD1 to effectively eliminate fumonisin biosynthesis. Additionally, we showed that the FvABC3 (FVEG_11089) mutant, earlier described as hypersensitive to pyrrocidine, is particularly sensitive to pyrrocidine B. Thus, pyrrocidine A and B show different target specificity (FvZBD1 or FvABC3) and synergistic action. These findings will help inform the optimization of maximally efficacious S. zeae strains for eliminating F. verticillioides colonization and fumonisin contamination in maize cropping systems. This novel study contributes significantly to our knowledge of competitive microorganism relationships and the role of secondary metabolites in antagonistic fungal-fungal interactions.
Novel silver nanoparticle-based biomaterials for combating Klebsiella pneumoniae biofilms
Authors: Elashkar Eslam , Alfaraj Rihaf , El-Borady Ola M. , Amer Mahmoud M. , Algammal Abdelazeem M. , El-Demerdash Azza S.
Published: January 2025

Background

Klebsiella pneumoniae is a significant nosocomial pathogen that has developed resistance to multiple antibiotics, often forming biofilms that enhance its virulence. This study investigated the efficacy of a novel nanoformulation, AgNPs@chitosan-NaF, in combating K. pneumoniae biofilms.

Methods

Antimicrobial susceptibility testing was performed to assess the antibiotic resistance profile of K. pneumoniae isolates. The antibiofilm activity of AgNPs@chitosan-NaF was evaluated using crystal violet staining and scanning electron microscopy. The underlying mechanisms of action were investigated through gene expression analysis.

Results

The majority of K. pneumoniae isolates exhibited high levels of multidrug resistance. AgNPs@chitosan-NaF demonstrated superior biofilm inhibition compared to AgNPs@chitosan, significantly reducing biofilm biomass and disrupting biofilm architecture at MICs ranging from 0.125 to 1 μg/mL. Mechanistic studies revealed that the nanoformulation downregulated the expression of key biofilm-associated genes, including treC, fimA, mrkA, and ecpA. While AgNPs@chitosan-NaF exhibited a concentration-dependent cytotoxic effect on both normal and cancer cell lines, minimal cytotoxicity was observed at concentrations below 31.25 μg/mL.

Conclusion

This study highlights the synergistic effect of silver nanoparticles, chitosan, and sodium fluoride in combating K. pneumoniae biofilms. The nanoformulation, AgNPs@chitosan-NaF, emerges as a promising therapeutic strategy to address the challenge of multidrug-resistant bacterial infections.
Multidrug efflux pumps of Pseudomonas aeruginosa show selectivity for their natural substrates
Authors: Mazza Léna , Bory Alexandre , Luscher Alexandre , Kloehn Joachim , Wolfender Jean-Luc , van Delden Christian , Köhler Thilo
Published: January 2025

Antibiotic-resistant Gram-negative bacteria are an increasing threat to human health. Strategies to restore antibiotic efficacy include targeting multidrug efflux pumps by competitive efflux pump inhibitors. These could be derived from natural substrates of these efflux systems. In this work, we aimed to elucidate the natural substrates of the clinically relevant Mex efflux pumps of Pseudomonas aeruginosa by an untargeted metabolomic approach. We constructed a PA14 mutant, genetically deleted in the major multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexXY-OprM, and MexEF-OprN and expressed in this mutant each efflux pump individually from an inducible promoter. Comparative analysis of the exo-metabolomes identified 210 features that were more abundant in the supernatant of efflux pump overexpressors compared to the pump-deficient mutant. Most of the identified features were efflux pump specific, while only a few were shared among several Mex pumps. We identified by-products of secondary metabolites as well as signaling molecules. Supernatants of the pump-deficient mutant also showed decreased accumulation of fatty acids, including long chain homoserine lactone quorum sensing molecules. Our data suggests that Mex efflux pumps of P. aeruginosa appear to have dedicated roles in extruding signaling molecules, metabolic by-products, as well as oxidized fatty acids. These findings represent an interesting starting point for the development of competitive efflux pump inhibitors.
Contrast-enhanced ultrasound of collecting duct carcinoma in the renal: a case report misdiagnosed as renal abscess on computed tomography scan
Authors: Luo Yunhao , Zhang Jing , Wu Minggang , Huang Qiuyun , Liu Fangqin , Qiao Lang
Published: January 2025

Collecting duct carcinoma (CDC), also known as Bellini duct carcinoma, is a rare malignancy with significant challenges in early diagnosis. This paper presents a case report of CDC that was misdiagnosed as renal abscess on computed tomography (CT). A 49-year-old male patient was admitted to the hospital with bilateral lumbar pain, exacerbated on the left side, accompanied by hematuria. Following laboratory tests, CT scan, ultrasound, and contrast-enhanced ultrasound (CEUS), the CT diagnosis was renal abscess, whereas CEUS suggested a malignant tumor. After a multidisciplinary discussion, the patient underwent surgery and was diagnosed with CDC. Previous studies indicate that two-dimensional ultrasound of CDC often lack typical features, while CT and magnetic resonance imaging (MRI) scan usually show mild enhancement. CEUS has a unique advantage in visualizing the microvasculature, which aids in the diagnosis of CDC.
Infantile epileptic spasms syndrome: an etiologic study of 361 patients with infantile epileptic spasms syndrome
Authors: Zhu Linghui , Xia Yuan , Ding Hao , Zhang Tong , Li Jun , Li Baomin
Published: January 2025

Introduction

Infantile Epileptic Spasms Syndrome (IESS) typically has a profound impact on the neurodevelopment of patients. The study on IESS indicates possible geographical variation in etiology and a lack of data from China. Our study intends to summarize the etiology of IESS and analyze its characteristics.

Methods

A retrospective analysis was performed to gather clinical data from patients diagnosed with IESS at the Department of Neurology of Qilu Hospital of Shandong University and the Children's Hospital Affiliated to Shandong University between June 2017 to May 2024.

Results

A total of 361 patients with IESS were included, comprising 115 structural cases (31.9%), 37 genetic cases (10.2%), 32 genetic-structural cases (8.9%), 9 metabolic cases (2.5%), 3 infectious cases (0.8%), and 165 cases with unknown etiology (45.7%). No immunological cause was determined. The primary cause of the condition was linked to hypoxic-ischemic encephalopathy (HIE), with structural brain abnormalities following closely. The predominant pathogenic genes identified were TSC2, NF1, SCN8A, and KCNQ2. Male gender, preterm infants, low birth weight infants, and developmental regression in patients were associated with a higher likelihood of structural etiology. Patients exhibiting developmental regression before the commencement demonstrated inferior outcomes. Patients administered adrenocorticotropic hormone (ACTH) exhibited a higher likelihood of attaining seizure control, and those who responded favorably to the medication saw improved results.

Conclusion

The predominant etiology of IESS is structural, succeeded by genetic factors, with significant pathogenic genes comprising TSC2, NF1, SCN8A, and KCNQ2. The genetic classifications exhibit geographic variability. Genetic and structural etiologies are frequently linked to an unfavorable prognosis. Genetic testing can help clarify the etiology of IESS when metabolic screening and brain MRI results are negative. The advancement of genetic testing is crucial for future targeted and individualized diagnosis and therapy.
Association of early aspirin use with 90-day mortality in patients with sepsis: an PSM analysis of the MIMIC-IV database
Authors: Huang Chunsheng , Tong Qiaoling , Zhang Wenyuan , Pan Zhihao
Published: January 2025

Objective

In addition to its antiplatelet and anti-inflammatory properties, aspirin inhibits bacterial proliferation directly. The potential benefits of aspirin may enhance the prognosis for sepsis patients. However, little is known about the effects of early aspirin administration. This study aimed to examine the correlation between the administration of aspirin at an early stage and the 90-day mortality rate among sepsis patients.

Methods

In order to distinguish between septic patients who received early aspirin treatment and those who did not, queries were conducted on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The principal metric utilized was 90-day mortality. We determined the association between early aspirin use and 90-day mortality using multivariate Cox regression, and propensity score matching (PSM) was utilized to validate our findings. The analyses of the subgroups have been completed.

Results

Our analysis comprised 28,425 septic patients, of whom 7,568 (26.6%) received aspirin within 24 h of intensive care unit (ICU) admission. The aspirin users group had a lower 90-day mortality than the aspirin nonusers group [1,624 (21.8%) vs. 2,035 (27.3%), P < 0.001]. The logistic regression showed that early aspirin use was associated with a lower 90-day mortality (OR, 0.74, 95% CI, 0.69–0.80, P < 0.001). K-M curve analysis showed that the 90-day mortality of the aspirin users group was significantly lower than that of the aspirin nonusers group (P < 0.001). Subgroup analysis revealed comparable relationships between early aspirin use and 90-day mortality among individuals.

Conclusion

In conclusion, early aspirin use was associated with decreased in-hospital and 90-day mortality in septic patients, emphasizing the significance of early aspirin use administration in the ICU.
Functions of METTL1/WDR4 and QKI as m7G modification - related enzymes in digestive diseases
Authors: Zhou Wenyan , Yi Yan , Cao Wenyu , Zhong Xiaolin , Chen Ling
Published: January 2025

N7-methylguanosine (m7G) modification is one of the most prevalent forms of chemical modification in RNA molecules, which plays an important role in biological processes such as RNA stability, translation regulation and ribosome recognition. Methyl-transferation of m7G modification is catalyzed by the enzyme complex of methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4), and Quaking (QKI) recognizes internal m7G methylated mRNA and regulates mRNA translation and stabilization. Recent studies have found that m7G modification - related enzymes are associated with the onset and progression of digestive cancer, such as colorectal cancer, liver cancer, and other digestive diseases such as ulcerative colitis. This review will focus on the latest research progress on the roles of m7G methyltransferase METTL1/WDR4 and recognized enzyme QKI in digestive diseases.