bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATG5-mediated keratinocyte ferroptosis promotes M1 polarization of macrophages to aggravate UVB-induced skin inflammation
Authors: Chen Xu , Xiao Ta , Liang Jinfeng , Li Min , Guo Yiming , Chen Sihan , Ke Yangying , Gao Xiang , Gu Heng 
Published: January 2024

Abstract
Autophagy participates in the regulation of ferroptosis. Among numerous autophagy-related genes (ATGs), ATG5 plays a pivotal role in ferroptosis. However, how ATG5-mediated ferroptosis functions in UVB-induced skin inflammation is still unclear. In this study, we confirm that the core ferroptosis inhibitor GPX4 is significantly decreased in human skin tissue exposed to sunlight. We report that ATG5 deletion in mouse keratinocytes strongly protects against UVB-induced keratinocyte ferroptosis and skin inflammation. Mechanistically, ATG5 promotes the autophagy-dependent degradation of GPX4 in UVB-exposed keratinocytes, which leads to UVB-induced keratinocyte ferroptosis. Furthermore, we find that IFN-γ secreted by ferroptotic keratinocytes facilitates the M1 polarization of macrophages, which results in the exacerbation of UVB-induced skin inflammation. Together, our data indicate that ATG5 exacerbates UVB-induced keratinocyte ferroptosis in the epidermis, which subsequently gives rise to the secretion of IFN-γ and M1 polarization. Our study provides novel evidence that targeting ATG5 may serve as a potential therapeutic strategy for the amelioration of UVB-caused skin damage.
RNA Nanotherapeutics with Fibrosis Overexpression and Retention (FORT) for NASH Treatment
Authors: Miao Lei , Shan Xinzhu , Zhao Zhiqiang , Lai Pingping , Liu Yuxiu , Li Buyao , Ke Yubin , Jiang Hanqiu , Zhou Yilong , Li Wenzhe , Wang Qian , Qin Pengxia , Xue Yizhe , Zhang Zihan , Wei Chenlong , Ma Bin , Liu Wei , Luo Cong , Lu Xueguang , Lin Jiaqi , Shu Li , Jie Yin , Xian Xunde , Delcassian Derfogail , Ge Yifan 
Published: January 2024

Abstract

Fibrotic diseases, like non-alcoholic steatohepatitis (NASH), pose challenges for targeted delivery and retention of therapeutic proteins due to increased extracellular matrix (ECM) deposition. Here we present a new approach to treat fibrotic diseases, termed “Fibrosis overexpression and retention (FORT)”. In this two-step strategy, we design 1) a retinoid derivative lipid nanoparticle (LNP) to enable specific mRNA overexpression in hepatic stellate cells, and 2) mRNA modifications which facilitate anchoring of therapeutic proteins in the fibrotic ECM. LNPs containing carboxyl retinoid derivatives, as opposed to alcohol or ester retinoid derivatives, effectively delivered mRNA, resulting in more than 10- fold enhancement of protein expression within the fibrotic liver. The carboxyl retinoid rearrangement on the LNP surface improved protein binding, sprouting, and membrane fusion. Therapeutic relaxin fusion proteins were then engineered with an endogenous collagen-binding domain. These fusion proteins exhibited increased retention in fibrotic lesions and reduced systemic side effects. In vivo, fibrosis-targeting LNPs encoding for mRNA fusion proteins demonstrated superior therapeutic efficacy in three clinically relevant NASH mouse models. This approach holds promise in chronic fibrotic diseases that are unsuited for direct injections of recombinant proteins.
The re-emergence of sexually transmissible multidrug resistant Shigella flexneri 3a, England, United Kingdom
Authors: Mason Lewis , Charles Hannah , Thorley Katie , Chong Charlotte , De Silva P. Malaka , Jenkins Claire , Baker Kate 
Published: January 2024

Abstract

Shigellosis is an enteric infection that transmits through the faecal-oral route, which can occur during sex between men who have sex with men (MSM). Between 2009 and 2014, an epidemic of sexually transmissible Shigella flexneri 3a occurred in England that subsequently declined. However, from 2018 to 2021, despite restrictions to control SARS-CoV-2 spread, S. flexneri 3a re-emerged. We explored possible drivers of the re-emergence by comparing host demographic features and pathogen genomics. The age and geographical distribution of cases in 2009–2014 (relative to 2018–2020) was comparable, with cases primarily among 35–64 year old men in London and the Southeast, a majority (54%) of which self-identified as gay or bisexual. Genomic analyses of 502 bacterial isolates showed that the majority (58%) of re-emerging MSM strains were a clonal replacement of the original lineage, with a reduced antimicrobial resistance profile. Specifically, more recent isolates had lost blaTEM−1 and erm(B), likely in line with shifting antimicrobial selection pressures. The absence of major changes in the pathogen or host demographics suggest that other factors, such as host immunity, may have driven the re-emergence of S. flexneri 3a and highlight the need for further work in the area.
Probing charge redistribution at the interface of self-assembled cyclo-P5 pentamers on Ag(111)
Authors: Pawlak Rémy , Chahib Outhmane , Yin Yulin , Liu Jung-Ching , Li Chao , Glatzel Thilo , Ding Feng , Yuan Qinghong , Meyer Ernst 
Published: January 2024

Abstract

Phosphorus pentamer (cyclo-P5-) ions are unstable in nature but can be synthesized at the Ag(111) surface. Unlike monolayer black phosphorous, little is known about their electronic properties when in contact with metal electrodes, although this is crucial for future applications. Here we characterize the atomic structure of cyclo-P5 assembled on Ag(111) using atomic force microscopy with functionalized tips and density functional theory. Combining force and tunneling spectroscopy, we find that a strong charge transfer induces an inward dipole moment at the cyclo-P5/Ag interface as well as the formation of an interface state. We probe the image potential states by field-effect resonant tunneling and quantify the increase of the local change of work function of 0.46 eV at the cyclo-P5 assembly. Our results suggest that the high-quality of the cyclo-P5/Ag interface might serve as a prototypical system for electric contacts in phosphorus-based semiconductor devices.
Teaching Practices of Islamic Education Teachers in Improving Critical Thinking of Rural Students
Authors: Osman Siti Fatihah , Ajmain@Jima’ain Muhammad Talhah , Awae Fareed , Rahman Siti Nur Hadis A , Malek Mohammad Dzarul Hafiz Dol , Aripin Syaima'a 
Published: January 2024

Abstract
Critical thinking is imperative for educators grappling with the 21st-century education system, particularly in teaching and learning (PdPc). Islamic Religious Education Teachers (IRET) predominantly employ static teaching methods, hindering the application of critical thinking in traditional lessons adhering to the syllabus. This study investigates how IRET integrates critical thinking into 21st-century learning skills (PAK-21), emphasizing sustainability. Employing a qualitative case study, it involves semi-structured interviews, observations of IRET teaching, and document analysis. Purposive sampling identifies seven IRET and 14 students. Nvivo 12.0 analyzes themes and sub-themes. Findings confirm IRET's practice of critical thinking in PAK-21, revealing challenges like time constraints, student attitudes, and rural facility limitations. IRET addresses these issues through innovation, diversified learning strategies, technology integration, knowledge amalgamation, staged teaching, student guidance, and role modelling. The study proposes a practical model for fostering critical thinking in PAK-21, meeting contemporary needs. Implications extend to Malaysian Ministry of Education policies and IRET practices, enhancing 21st-century teacher professionalism sustainably. This research advocates for an educational paradigm shift towards critical thinking, ensuring adaptability and relevance in a rapidly changing world.
Allergen-specific immunotherapy with Der p 1/2 mRNA vaccines alleviates house dust mite-induced allergic airway inflammation in a mouse model
Authors: Yin Jia , Li Junda , Yi Xilian , Guan Kai , xiaogang li 
Published: January 2024

Abstract

Allergen-specific immunotherapy is the only treatment that alters the natural course of allergic diseases and provides long-term therapeutic effects. Current treatments are based on crude allergen extracts, which contain various complex components and lack standardization, significantly affecting the safety and efficacy of AIT. With the success of mRNA vaccines, allergen-specific mRNA vaccines could prove to be a viable treatment approach. We screened major house dust mite allergens mRNA sequences in 293T cells and prepared three mRNA vaccines, then tested the safety and efficacy of AIT with these vaccines in a house dust mite-induced allergic airway mouse model. House dust mite-sensitized mice underwent subcutaneous immunotherapy with a house dust mite extract, mRNA vaccines, or placebo. Subsequent to the AIT and challenge, we assessed body temperature, allergen-induced ear swelling, specific immunoglobulin response, inflammatory cells in bronchoalveolar lavage fluid and lung tissues, and cellular immune responses in the spleen, mediastinal lymph nodes, and lungs. Der p 1- and Der p 2 mRNA were successfully expressed in 239T cells and induced specific IgG antibodies in mice. Body temperature monitoring revealed no signs of anaphylaxis following the first subcutaneous injection of either vaccine. Ear swelling response measurements indicated suppression of an early allergic reaction in Der p 2 mRNA-treated mice. All groups demonstrated the ability to suppress airway inflammation and eosinophilic infiltration. Strong differentiation of regulatory T cells and increased effective regulation of the Th1/Th2 balance were observed in mRNA-treated mice. These data suggest that mRNA vaccines represent a potential novel approach for the development of AIT treatments.
Identification and characterization of four novel xiaomi alleles to facilitate foxtail millet as a C4 model plant
Authors: Shan Meng , Duan Mengmeng , Shen Huimin , Wang Yujing , Zhang Yiru , Li Xukai , Han Yuanhuai , Yang Zhirong , Zhao Kai , Wang Xingchun 
Published: January 2024

Abstract
Diverse genetic background is essential for genetic analysis and functional genomics research in model plants. In this paper, four novel xiaomi-like mutants, named xiaomi3, xiaomi4, xiaomi5, and xiaomi6, were identified and characterized in different genetic backgrounds. These mutants exhibited an extremely early heading phenotype, with heading occurring around 30-40 days after sowing under natural long-day conditions. Significant reductions in plant height, leaf length, leaf width, panicle length, and panicle diameter were observed in the mutants compared to their corresponding wild-types. Notably, these mutants displayed diverse panicle architectures and hull colors, effectively preventing seed mixing between them. Subsequent investigation under controlled short-day and long-day conditions confirmed the significant early heading phenotype of the mutants. Molecular characterization revealed mutations in the Phytochrome C (SiPHYC) gene, including transposon insertions and a frame shift mutation, were responsible for the extremely early heading phenotype. RNA-sequencing (RNA-Seq) analysis identified 19 differentially expressed genes associated with the extremely early heading phenotype. Additionally, genome-wide InDels and SNPs were identified, providing valuable resources for marker-assisted breeding and genetic studies. These findings advance our comprehension of the genetic and molecular mechanisms underlying SiPHYC mediated photoperiod flowering, and provide valuable resources that will push xiaomi as a C4 model plant.
Examining the relationship between problematic pornography use and mental health status among adolescents of Bangladesh
Authors: Rimti Fahmida Hoque , Ripon Rezaul Karim , Zubayer Abdullah Al , Rimu Fariha Hoque , Rahman Quazi Maksudur , Nailah Mustari Tabassum , Rahman Tareq , Sarkar Tanzeema Younus , Islam Md. Rafiqul , Das Tirthom , Nipun Khairul Islam , Sabuz Md. Shahriar , Akhter Ishita , Nandi Ashim Kumar , Ilman Ahnaf , Hawlader Mohammad Delwar Hossain 
Published: January 2024

Abstract

Background: Pornographic use has been associated with poor mental health consequences. This cross-sectional study aimed to examine the relationship between problematic pornography use and mental health issues among adolescents in Bangladesh.
Methods: This study employed a cross-sectional design to evaluate the relationship between problematic pornography uses with mental health status of adolescents in Bangladesh. The survey, which involved demographic questions and scales like the University of California, Los Angeles (UCLA) Loneliness Scale, the Multidimensional Scale of Perceived Social Support (MSPSS), the General Anxiety Disorder-7, and the Brief Pornography Screen, included a sample of 601 teenagers. Data were analyzed using hierarchical linear regression models after the scales underwent step-by-step validation.
Results: It was discovered that boys scored higher (6.71) than girls (3.16), with the mean score for problematic pornography use (PPU) being 5.13. The Brief Pornography Scale revealed substantial relationships with anxiety (r=0.358), loneliness (r=0.382), and perceived social support (r=0.276). The structural modeling equation and hierarchical linear regression analysis showed that problematic use of pornography was associated with being male (r=0.26 to 0.45, p=0.001), higher monthly family cost (r=0.12 to 0.33, p=0.05), accessing pornography online (r=-0.14 to -0.27, p=0.05), consuming pornography through TV/DVD/downloaded videos (r=-0.44 to -0.55). However, the RSES scale did not reveal any correlation between problematic pornography consumption and self-esteem.
Conclusion: This study found significant relationship with problematic pornography use and mental health status of Bangladeshi adolescent. It emphasizes the significance of raising awareness about the danger of problematic pornography use. The results of this study highlight the necessity for focused interventions and educational initiatives addressing the possible hazards connected to this population's pornographic use.
Differences in outcomes of patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation between day-time and night-time
Authors: Koguchi Hazuki , Takayama Wataru , Otomo Yasuhiro , Morishita Koji , Inoue Akihiko , Hifumi Toru , Sakamoto Tetsuya , Kuroda Yasuhiro 
Published: January 2024

Abstract

Although patients who underwent night-time resuscitation for out-of-hospital cardiac arrest (OHCA) had worse clinical outcomes than those who underwent day-time resuscitation, the differences between the outcomes of patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR) in the day-time and night-time remain unclear. We analyzed data from the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan. Patients were categorized according to whether they received treatment during the day-time or night-time. The primary outcomes were survival to hospital discharge and favorable neurological outcome at discharge, and the secondary outcomes were estimated low-flow time, implementation time of ECPR, and complications due to ECPR. A multivariate logistic regression model adjusted for confounders was used for comparison. Among the 1,644 patients, the night-time patients had a significantly longer implementation time of ECPR and estimated low-flow time than the day-time patients, along with a significantly higher number of the complications than the day-time patients. However, the survival and neurologically favorable survival rates did not differ significantly between the groups. Thus, although patients who underwent ECPR at night had an increased risk of longer implementation time and complications, their clinical outcomes did not differ from those who underwent day-time ECPR.
Effects of Maintenance of Motor and Respiratory Performance With a Training Program in Inpatients Undergoing Bone Marrow Transplant
Authors: Bottani Chiara , Piazza Chiara 
Published: January 2024

Abstract
Background. Substantial physical and functional deconditioning are all potential adverse effects of bone marrow transplantation.
Objective. To observe how physiotherapy treatment during the hospitalization period can impact the maintenance of motor and respiratory performance in patients undergoing bone marrow transplantation.
Furthermore, it is interesting to evaluate how the patient is able to independently manage the proposed activity and consider it important for their health in the long term.
Methods. Patients underwent strength and endurance tests at the start, at the end of hospitalization, and two months after discharge. The patients were given a rehabilitation protocol to follow during the entire hospitalization. During this period, lasting approximately 21 days, the physiotherapist supervises the carrying out of the exercises twice a week. From discharge and for the two months of follow-up the patient carries out the proposed protocol independently.
Results. Forty-four patients were tested upon admission, discharge, and two months after admission. The distance covered in the walking test remains constant.
The strength of the upper limbs shows a slight flexion at discharge and recovery of the initial values after eight weeks. The power of the lower limbs remains constant during hospitalization and increases with remote control.
Conclusion. The results show that the proposal of moderate intensity physical activity can help maintaining motor and respiratory performance, in patients undergoing bone marrow trasplantation.
A novel COL2A1 mutation (c.1888G&gt;T(p.Gly630Cys)) in a Chinese family with Avascular necrosis of the femoral head
Authors: Wei Zhuoqun , Zhu Liulong 
Published: January 2024

Abstract

Background: Familial avascular necrosis of the femoral head (ANFH) was a complex and complicated orthopedic disorder that cause changes in the structure of type II collagen due to a pathogenic mutation in the COL2A1 gene. With the damage to cartilage and bone, the disease gradually deteriorated into familial ANFH. The reports of familial ANFH were extremely rare. Besides, misdiagnosis and missed diagnosis are extremely likely to occur due to the difficulty of diagnosis.
Case presentation: A 54-year-old woman developed soreness and pain in her right hip five months before admission without any apparent cause. The above symptoms suddenly worsened after four-month, and she was diagnosed with avascular necrosis of the femoral head (ANFH). The radiograph and MRI images (anteroposterior view) results of the pelvis and hip joints of the patient showed ANFH in stage II (based on the standard table of ARCO).
whole-exome sequencing and analysis were conducted with the consent of family members. After Carrying out whole exon sequencing and analysis and selecting candidate gene mutations for ANFH in chr12. Then, we sequenced exonic regions of the type II collagen gene (COL2A1) from patients with inherited and sporadic forms of ANFH.
The mutation in COL2A1 gene on chr12 was determined by analyzing and examining candidate genes. A C→A transition in COL2A1 gene was detected in II-7, III-11, III-13, IV-5 and IV-6 family members. This transition caused the replacement of glycine with cysteine in (Gly-X-Y)n region. Sanger sequencing was performed to verify the above mutation and the results are consistent with the above conclusion.
Conclusions: This case was from China. Findings from imaging showed that there were significant differences between familial ANFH and general ANFH. These differences were most likely due to unique phenotypes resulting from pathogenic mutations in the COL2A1 gene. The result found that a new mutation type c.1888G>T(p.Gly630Cys) may cause significant distortion of Collagen Triple-Helix Structure, which had not been reported previously. This study revealed a novel and potential mutation leading to femoral head necrosis, which provides an imaging and molecular basis for the diagnosis and timely treatment in additional members of the family.
Histopathological evaluation of PYGO2 expression in esophageal squamous cell carcinoma
Authors: Khales Sima Ardalan , kalat Habibeh Rahmani , Soleymani Sedigheh , Jafarian Amir Hossein , Forghanifard Mohammad Mahdi 
Published: January 2024

Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is one of the world's deadliest cancer diseases. Deregulation of developmental signaling pathways such as Wnt/β-catenin is frequently implicated in a wide range of human cancers. The present study was designed to analyze the expression of the Pygopus2 (PYGO2) protein, the main co-activator of the Wnt/β-catenin signaling pathway, in ESCC tissues and evaluate its probable correlation with clinic-pathological features of patients.
Materials and Methods: In this study, PYGO2 protein expression was assessed in tumors and margin normal tissues from 50 ESCC patients using immunohistochemistry (IHC) analysis.
Results: Significant PYGO2 overexpression was observed in %94 tumor cells. Interestingly, PYGO2 expression was significantly correlated with the depth of tumor invasion (p= 0.021). Considering the significant expression of PYGO2 protein in ESCC cells and its correlation with tumor invasion.
Conclusion: This protein may be used as a biomarker for diagnosis of invasive ESCC, as well as a putative therapeutic target to inhibit ESCC invasiveness.
Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation
Authors: Zhou Zhengli , Wu Xiaomei , Cheng Tingwei , Zhang Bo , Li Wenxin , Zhou Min , Zhao Jinxue , Dong E , Li Tianqing 
Published: January 2024

Abstract
Background: Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating IUA.
Methods: Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assays, trilineage differentiation experiments, and decidualization assays were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreting cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis.
Results: We successfully isolated EnSCsfrom the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained sex hormones responsiveness. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and regeneration factor secretion.
Conclusions: Due to the large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury induced IUA.