bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Trace Elements and Antimycotics to Manage Rice Blast Disease Caused by Pyricularia oryzae
Authors: Maira Fatima , Sahi Shahbaz T. , Ali Safdar , Khan Muhammad A.
Published: May 2024

Rice blast disease caused by Pyricularia oryzae causes significant yield losses. Sixteen commercial cultivars of fine rice from Rice Research Institute, Kala Shah Kaku, Punjab, Pakistan were assessed for genomic resistance years as well as the efficacy of trace elements and antimycotics for two consecutive years (2021-22).  Two varieties (Super Basmati and Basmati-370) were found highly susceptible, while KSK 133 was observed resistant, RC-8, CHECK, RC-7, PKBR21-8 and PK11876-1-2 were moderately resistant, KSK-282, RC-6, PKBR21-12,PKBR2-1 and PK11661-2-3 were moderately susceptible and the variety C1,C2 and C3 were susceptible against the disease. In management of the disease, combination of thiophanate methyl, tebuconazole + trifloxystrobin, and fosetyle-aluminium was more effective with minimum disease severity of 11.89% and 11.69%.  In a moderatley susceptible vareity the application of thiophanate methyl and fosetyle-aluminium also effectively suppressed the disease severity 17.83% and 16.90% respectively. Tebuconazole + trifloxystrobin combination was less effective against the disease (36.67% and 36.51%). The combination of copper, zinc, and boron suppressed the disease to the maximum with disease severity of 9.681% and 9.62%. Overall, respective combinations of both fungicides and trace elements were found to be the most effective in controlling rice blast disease
Role of Arbuscular Mycorrhiza (AM) Fungi and Lignin in Biological Control against Vascular Fusarium Wilt Disease
Authors: Yasir Mahdi S. , Taha Zainab K. , Hassan Fadia F. , Muhsen Thamer A. A.
Published: May 2024

The current study aimed to assess the biological efficacy of the triple arbuscular mycorrhiza (AM) mixture of fungi Glomus etunicatum, G. leptotichum and Rhizophagus intraradices, and mix it with organic matter (O) and pathogenic fungi Fusarium oxysporum f.sp.lycopersici by using voyeurism in the plastic house in the growth of the tomato plant after four and eight weeks of cultivation. The results were shown after the treatment of the tomato plant in agriculture with the mixture of mycorrhiza and the pathogenic fungi and organic matter were treated with the mixture of mycorrhiza, organic matter and pathogenic fungi together. The effect of mycorrhiza and organic matter interference on the increase in the percentage of the lignin after eight weeks was very clear. The effect of the mycorrhiza mixture, organic matter and the pathogenic fungi in the percentage of disease incidence on the leaves and roots of the tomato plant, a relative decrease in infection was observed after two and four weeks of cultivation and the percentage of the death of the plant gestures contaminated with the pathogen was low after four weeks transplantation as a result of the effect of the mycorrhiza mixture and organic matter on it
Mekân ve Toplumsal Cinsiyet Bağlamında Konya Kadınlar Pazarının Dönüşümü
Authors: Atmaca Çetinkaya Merve , Tekdemir Dokeroglu Ozlem
Published: May 2024

Yerel yaşam ve ticaret kültürün önemli bir parçası olan Konya Kadınlar Pazarı üzerine güncel bir bakış açısı oluşturabilme amacıyla yola çıkan bu araştırma, belirli bir alanda varlığından haberdar olunan, kentinin sosyokültürel yapısıyla birlikte farklılaşan bu yapının, mekân ve toplumsal cinsiyet bağlamındaki dönüşüm ve değişimini odağına alır. Araştırma ayrıca 120 yıla yakın süredir yaşayan bir çarşı geleneğinin toplumsal cinsiyet açısından, kadın esnaf olgusu odağında nasıl değiştiğini ve çarşının yer aldığı mekânın çevresel dönüşümünü incelemeye odaklanır. Araştırmanın konusu olan Kadınlar Pazarı, Konya gibi medeniyet geçmişi zengin bir şehir için mekân olarak eski sayılmasa da simgesel özellikler taşıyan bir yapı olması, çarşı yapılanması için bir merkez oluşturması ve toplumsal cinsiyet kavramı üzerine bir örneklem sunabilmesi açısından önemlidir. Bu bağlamda araştırma, bu konuda farklı disiplinlerde yapılmış araştırmalardan da referanslar alarak konuyu yeniden gündeme taşıma ve mekânın bugünkü durumu ile ilgili bir farkındalık oluşturabilmeyi de başka bir amaç olarak benimser. Çalışmanın yöntemini literatür taraması, saha araştırması ve gözlem oluşturmaktadır.
Queuing Model at LPG Bulk Filling and Transportation Station (SPPBE) Pt. Agrabudi Gas Utama, Barito Kuala Regency, South Kalimantan
Authors: Patrisia Yolanda , Triyanto Irfan Rusydi , Abdullah Ishlahuddin
Published: May 2024

Background: LPG is fuel in the form of natural gas which is liquefied into LPG (Liquefied Patroleum Gas) and is an environmentally friendly petroleum product and is widely used by households and micro businesses. LPG is a popular fuel among the upper middle class. Various tube sizes are 3 kg, 5 kg and 12 kg. PT. LPG Bulk Transport and Filling Station (SPPBE). Agrabudi Gas Utama is one of the places to refill LPG gas, especially for 3 kg LPG gas in Barito Kuala district. In this research, a Multi Channel Single Phase system is used, namely there is one queue line and two or more service facilities which are implemented sequentially. Multi Channel Single Phase has several service facilities at each stage. So more than one individual can be served at a time.
Objective: The aim of this research is to save on kerosene subsidies and improve service performance by knowing the number of service facilities and optimal service times at the PT LPG Bulk Transport and Filling Station (SPPBE). Agrabudi Gas Utama.
Method: This research method is a type of research using primary data, namely by obtaining it from the company through observation and recording during field observations.
Result: Based on the results of observations made during research into the service process at SPPBE PT. Agrabudi Gas Utama applies a multichannel singlephase queue structure model, which means SPPBE PT. Agrabudi Gas Utama only has one service facility and one channel.
Conclusion: Conclusions from research carried out at SPPBE PT. Agrabudi Gas Utama is the arrival and service rate is 2.58 trucks/hour, the average truck processing time is 28.8 minutes and the expected time for trucks in the filling process is 73.92 minutes.
Detection of calcitonin gene-related peptide based on increased antigen-driven interaction with antibody variable regions
Authors: Cheng Yueqing , Gao Yujie , Zhang Shengshuo , Zou Yujie , Zhao Guangwei , Zheng Liyuan , Hou Binghui , Li Mei , Dong Jinhua
Published: May 2024

Introduction: Calcitonin gene-related peptide (CGRP) is involved in trigeminal neuralgia and migraine, and measuring the CGRP concentration in the serum is crucial for the early prediction of these conditions. Current methods for CGRP detection are primarily radioimmunoassay, which needs radioactive substances and enzyme-linked immunosorbent assays (ELISAs) which need long detection time and some have a narrow detection range.

Methods: The genes of anti-CGRP antibody variable regions were cloned into pDong1 vector to obtain pDong1/Fab-CGRP, with which phage-Fab was prepared, and the concentration of CGRP was detected by competitive ELISA. The pDong1/Fab-CGRP was modified to obtain pDong1/OS-CGRP, with which the co-expression solution containing phage-displayed heavy chain variable fragments (phage-VH) and light chain was obtained. CGRP was detected by OS-ELISA based on phage-VH, antibody light chain, and anti-light chain antibody. The VL gene was cloned into the pMAL vector to obtain pMAL-VL (CGRP), with which maltose binding protein fused with VL (MBP-VL) was prepared. CGRP was detected by OS-ELISA employing MBP-VL and phage-VH.

Results: OS-ELISAs that measure the CGRP concentration by quantifying the interaction between variable regions were investigated. OS-ELISA using phage-VH and secreted light chains in the same culture system exhibited a limit of detection (LOD) of 0.05 nM, offering higher sensitivity than competitive assay with an LOD of 0.75 nM, whereas using phage-VH and separately prepared MBP-VL exhibited an LOD of 0.15 nM and a broader detection range of 0.15–500 nM than competitive ELISA, whose detection range was 0.75–10 nM.

Discussion: The combination of the two OS assays achieved high sensitivity and a broad detection range for CGRP, which may have significance in clinical applications.
Proteomic analysis and functional validation reveal distinct therapeutic capabilities related to priming of mesenchymal stromal/stem cells with IFN-γ and hypoxia: potential implications for their clinical use
Authors: Calligaris Matteo , Zito Giovanni , Busà Rosalia , Bulati Matteo , Iannolo Gioacchin , Gallo Alessia , Carreca Anna Paola , Cuscino Nicola , Castelbuono Salvatore , Carcione Claudia , Centi Claudio , Amico Giandomenico , Bertani Alessandro , Chinnici Cinzia Maria , Conaldi Pier Giulio , Scilabra Simone Dario , Miceli Vitale
Published: May 2024

Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice.
Molecular and therapeutic advancements in Capicua (CIC)-rearranged sarcoma
Authors: Ponce Rovingaile Kriska M. , Luck Cuyler , Okimoto Ross A.
Published: May 2024

Capicua (CIC)-rearranged sarcomas are an aggressive subset of undifferentiated round cell sarcomas. CIC::DUX4, the proto-typical CIC fusion oncoprotein is associated with rapid clinical progression and chemotherapy resistance leading to poor clinical outcomes. Recent studies have identified additional CIC fusions (CIC::NUTM1, CIC::FOXO4, and CIC::LEUTX) that largely retain CIC-binding specificity but leverage C-terminal binding partners (NUTM1, FOXO4, and LEUTX) to potentially activate transcriptional programs that drive oncogenesis. Moreover, the recent development of preclinical models to study CIC::DUX4 sarcoma have advanced our understanding of the underlying biological mechanisms and uncovered key dependencies that can be translated into rational therapies. In this review, we will highlight these recent advancements in CIC-rearranged sarcoma biology with a vision for clinical translation to improve patient outcomes.
Prenylflavonoids isolated from Epimedii Herba show inhibition activity against advanced glycation end-products
Authors: Nakashima Keisuke , Miyashita Hiroyuki , Yoshimitsu Hitoshi , Fujiwara Yukio , Nagai Ryoji , Ikeda Tsuyoshi
Published: May 2024

Introduction: As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age-related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of Nε-(carboxymethyl)lysine (CML) and Nω-(carboxymethyl) arginine (CMA) during the incubation of collagen-derived gelatin with ribose.

Materials and methods: EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA.

Results: After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (1), Koreanoside E1 (2), and Koreanoside E2 (3)] and 40 known compounds (4–43) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (8), epimedonin E (21), epicornunin B (22), and epicornunin F (24) inhibited the formation of both CML and CMA, with epimedokoreanin B (8) having the most potent inhibitory effect among the isolated compounds. To obtain the structure–activity relationships of 8, the phenolic hydroxy groups of 8 were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of 8. Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay.

Discussion: As only 8 showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that 8 could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs.
The recent advances in the approach of artificial intelligence (AI) towards drug discovery
Authors: Khan Mahroza Kanwal , Raza Mohsin , Shahbaz Muhammad , Hussain Iftikhar , Khan Muhammad Farooq , Xie Zhongjian , Shah Syed Shoaib Ahmad , Tareen Ayesha Khan , Bashir Zoobia , Khan Karim
Published: May 2024

Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery.
Overlooked technological and societal trends that will level-up our fight against climate change
Authors: Beaumont Maximus L. L.
Published: May 2024

Our ability to fight COVID-19 demonstrates that where there’s a will, there’s a way. Yet proactive action will not be the single driving force behind us winning a stable and benign environment for our children. This article focuses on the not so obvious yet impactful trends affecting our ability to stave off the worst of climate change. These trends include carbon taxation, climate litigation, AI, space exploration, Direct Air Capture and an ever younger, more motivated demographic. Some trends will affect our efforts in unknown and unpredictable ways, while others will drive them with ever more force over the years to come. Carbon taxation requires a proactive change in government policy, but that change will place implementation in the hands of the free market. As we face an existential crisis never before seen by humanity, perhaps the largest driving force affecting our ability to ensure a healthy planet will be a more engaged public.
Optical coherence tomography-guided vs. intravascular ultrasound-guided percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials
Authors: Vats Vaibhav , Elahi Aarij , Hidri Sinda , Abdelkader Rem Ehab , Munaf Farhan , Prince Jennifer Mercika , Asif Muhammad Ahsan , Cheema Huzaifa Ahmad , Ahmad Adeel , Rehman Wajeeh Ur , Nashwan Abdulqadir J. , Ahmed Raheel , Lakhter Vladimir , Virk Hafeez Ul Hassan , Vincent Royce P.
Published: May 2024

Background

Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) are superior to coronary angiography for guiding percutaneous coronary intervention (PCI). However, whether one technique is superior to the other is inconclusive.

Methods

We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to November 2023 for randomized controlled trials (RCTs) comparing OCT and IVUS in patients undergoing PCI. RevMan 5.4 was used to pool outcomes with risk ratio (RR) as the effect measure.

Results

Six RCTs (4,402 patients) were included in this meta-analysis. There was no significant difference between the OCT- and IVUS-guided PCI groups in the risk of major adverse cardiovascular events (RR 0.87, 95% CI: 0.65, 1.16; I2 = 0%) and cardiac mortality (RR 0.73, 95% CI: 0.24, 2.21; I2 = 0%). The results were consistent across the subgroups of the presence or absence of left main disease (Pinteraction >0.1). There were no significant differences between OCT and IVUS in the risk of target lesion revascularization (RR 0.78, 95% CI: 0.47, 1.30; I2 = 0%), target vessel revascularization (RR 1.06, 95% CI: 0.69, 1.62; I2 = 0%), target-vessel myocardial infarction (RR 0.79, 95% CI: 0.40, 1.53; I2 = 0%), stent thrombosis (RR 0.59, 95% CI: 0.12, 2.97; I2 = 0%), and all-cause mortality (RR 1.01, 95% CI: 0.53, 1.90; I2 = 0%).

Conclusions

Our meta-analysis demonstrated similar clinical outcomes in OCT- and IVUS-guided PCI. New large-scale multicenter RCTs with long-term follow-up are required to confirm or refute our findings and provide more reliable results.

Systematic Review Registration

PROSPERO, identifier, CRD42023486933
Case Report: Lacosamide unmasking SCN5A-associated Brugada syndrome in a young female with epilepsy
Authors: Shen Ying-Chi , Wu Jen-Chueh , Lin Ting-Tse , Chang Kai-Chung , Su Jen-Jen , Juang Jyh-Ming Jimmy
Published: May 2024

Background

Lacosamide is frequently used as a mono- or adjunctive therapy for the treatment of adults with epilepsy. Although lacosamide is known to act on both neuronal and cardiac sodium channels, potentially leading to cardiac arrhythmias, including Brugada syndrome (BrS), its adverse effects in individuals with genetic susceptibility are less understood.

Case

We report a 33-year-old female with underlying epilepsy who presented to the emergency department with a four-day history of seizure clusters, and was initially treated with lacosamide therapy. During the intravenous lacosamide infusion, the patient developed sudden cardiac arrest caused by ventricular arrhythmias necessitating resuscitation. Of note, the patient had a family history of sudden cardiac death. Workup including routine laboratory results, 12-lead electrocardiogram (ECG), echocardiogram, and coronary angiogram was non-specific. However, a characteristic type 1 Brugada ECG pattern was identified by ajmaline provocation testing; thus, confirming the diagnosis of BrS. Subsequently, the genotypic diagnosis was confirmed by Sanger sequencing, which revealed a heterozygous mutation (c.2893C>T, p.Arg965Cys) in the SCN5A gene. Eventually, the patient underwent implantable cardioverter-defibrillator implantation and was discharged with full neurological recovery.

Conclusion

This case highlights a rare but lethal adverse event associated with lacosamide treatment in patients with genetic susceptibility. Further research is warranted to investigate the interactions between lacosamide and SCN5A variants.
Depletion of follicular B cell-derived antibody secreting cells does not attenuate angiotensin II-induced hypertension or vascular compliance
Authors: Figueiredo Galvao Hericka Bruna , Lieu Maggie , Moodley Seyuri , Diep Henry , Jelinic Maria , Bobik Alexander , Sobey Christopher G. , Drummond Grant R. , Vinh Antony
Published: May 2024

Introduction

Marginal zone and follicular B cells are known to contribute to the development of angiotensin II-induced hypertension in mice, but the effector function(s) mediating this effect (e.g., antigen presentation, antibody secretion and/or cytokine production) are unknown. B cell differentiation into antibody secreting cells (ASCs) requires the transcription factor Blimp-1. Here, we studied mice with a Blimp-1 deficiency in follicular B cells to evaluate whether antibody secretion underlies the pro-hypertensive action of B cells.

Methods

10- to 14-week-old male follicular B cell Blimp-1 knockout (FoB-Blimp-1-KO) and floxed control mice were subcutaneously infused with angiotensin II (0.7 mg/kg/d) or vehicle (0.1% acetic acid in saline) for 28 days. BP was measured by tail-cuff plethysmography or radiotelemetry. Pulse wave velocity was measured by ultrasound. Aortic collagen was quantified by Masson's trichrome staining. Cell types and serum antibodies were quantified by flow cytometry and a bead-based multiplex assay, respectively.

Results

In control mice, angiotensin II modestly increased serum IgG3 levels and markedly increased BP, cardiac hypertrophy, aortic stiffening and fibrosis. FoB-Blimp-1-KO mice exhibited impaired IgG1, IgG2a and IgG3 production despite having comparable numbers of B cells and ASCs to control mice. Nevertheless, FoB-Blimp-1-KO mice still developed hypertension, cardiac hypertrophy, aortic stiffening and fibrosis following angiotensin II infusion.

Conclusions

Inhibition of follicular B cell differentiation into ASCs did not protect against angiotensin II-induced hypertension or vascular compliance. Follicular B cell functions independent of their differentiation into ASCs and ability to produce high-affinity antibodies, or other B cell subtypes, are likely to be involved in angiotensin II-induced hypertension.
Validation of a Spanish version of the Foreign Language Classroom Anxiety Scale in Peruvian secondary education students
Authors: Quispe-Sanca Ruth V. , Arteta-Sandoval Gissel , Quispe-Sanca David , Morales-García Wilter C.
Published: May 2024

Background

Anxiety in learning foreign languages is a global phenomenon that impacts students’ academic performance, with English being a critical language in secondary education. The Foreign Language Classroom Anxiety Scale (FLCAS) has been widely used to assess this anxiety. However, the need to validate and adapt the scale for specific cultural contexts remains a priority in educational research.

Objective

To assess the validity and reliability of a Spanish version of the FLCAS among a sample of Peruvian secondary education students, in order to better understand the structure of language learning anxiety in this context.

Methods

A total of 818 students from four public educational institutions in southern Peru participated. An instrumental design was used, which included descriptive analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and assessments of convergent, divergent validity, and measurement invariance by gender.

Results

The EFA recommended a four-factor model that explained 32% of the total variance. Subsequent CFA adjusted this model to 24 items with optimal fit indices (CFI = 0.969; RMSEA = 0.045). The reliability of the factors was acceptable (α > 0.70 for all factors). Convergent and divergent validity was confirmed through significant correlations with related constructs (Fear of Negative Evaluation and Enjoyment of Foreign Language). Gender invariance analysis indicated that the scale is equally applicable to men and women.

Conclusion

The Spanish version of the FLCAS is a valid and reliable tool for assessing foreign language classroom anxiety among Peruvian secondary education students. This study contributes to the field of language teaching by providing evidence of the cultural applicability of the FLCAS in the Peruvian context, thus facilitating more effective pedagogical interventions to address language learning anxiety.
Alternative grading strategies in organic chemistry: a journey
Authors: Mio Matthew J.
Published: May 2024

The global pandemic forced educators at all levels to re-evaluate how they would engage content, generate relevance, and assess the development of their students. While alternative grading strategies were not necessarily new to the world of chemical education research (CER) in 2020, the pandemic accelerated the examination of such principles for instructors who wished to prioritize learning over compliance with course policies and eschew points for grading. This article describes the transformation of a traditional lecture organic chemistry course under new, standards-based principles. Working from a discrete set of grouped learning outcomes, these courses aim to clearly define standards, give helpful feedback, indicate semester-long student progress, and allow for reattempts without penalty using a token system. Students explore both core (all of which must be passed in order to show progress) and non-core (students can choose a majority of these to pass) learning outcomes in a variety of formative and summative assessment approaches. Unique to the reformatting of these courses is the use of collaborative, take-home assessments, integration of multiple-choice questions, ungrading of student-submitted summary notes, live solving of select problems with peer feedback, and a learning check system that reinforces the flipped nature of content delivery. Another distinctive feature of the courses is the requirement for students who reach a certain threshold of repeating learning outcomes to perform in-person problem solving for the instructor. Overall, students report that the structure of the courses reduces their general and specific anxiety, lowers the temptations to challenge their academic integrity, and increases their own learning self-monitoring, reflecting known pedagogies of metacognition. The instructor reports that alternative grading strategies take far less time, generates more meaningful feedback, and shifts student attitudes away from final grading and toward genuine learning.
Evaluation of the urban living lab in HEIs towards education for sustainable development (E-ULL-HEIs)
Authors: Morales Ivetheyamel , Segalás Jordi , Masseck Torsten
Published: May 2024

This study explores the implementation of Urban Living Labs (ULLs) in Higher Education Institutions (HEIs) to promote Education for Sustainable Development (ESD). It adopts a methodology that integrates a mixed approach, combining literature review, validation with experts in the field and analysis of case studies. A structured evaluation tool is proposed based on three constructs: Synergy, Strategy and Pedagogy, which cover the essential characteristics of the three thematic axes: ULLs, ESD and HEIs, through seven indicators. This tool is applied to examine the effective-ness of ULLs in promoting sustainable practices within the university context. The results, vali-dated through experts, exploratory factor analysis and Cronbach’s alpha coefficient, demonstrate the reliability and consistency of the evaluative indicators, highlighting the crucial role of ULLs in the integration of sustainability in the curriculum, experiential learning, and the impact social and community. This approach allowed the identification of successful practices and common challenges in the implementation of ULL, as well as the development of a framework of indicators adapted to the specific needs of HEIs. The study concludes by emphasizing the transformative potential of ULLs in HEIs to advance towards sustainable urban transitions, underscoring the need for robust evaluative tools to optimize the contribution of higher education to global sustainable development.
Role of miRNA-regulated type H vessel formation in osteoporosis
Authors: Zhang Dailiang , Wang Yongjing , Zhou Zunzhen , Wang Limei , Liu Chongzhi , Jiang Yuan
Published: May 2024

Osteoporosis (OP) is a chronic systemic bone metabolism disease characterized by decreased bone mass, microarchitectural deterioration, and fragility fractures. With the demographic change caused by long lifespans and population aging, OP is a growing health problem. The role of miRNA in the pathogenesis of OP has also attracted widespread attention from scholars in recent years. Type H vessels are unique microvessels of the bone and have become a new focus in the pathogenesis of OP because they play an essential role in osteogenesis-angiogenesis coupling. Previous studies found some miRNAs regulate type H vessel formation through the regulatory factors, including platelet-derived growth factor-BB (PDGF-BB), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and so on. These findings help us gain a more in-depth understanding of the relationship among miRNAs, type H vessels, and OP to find a new perspective on treating OP. In the present mini-review, we will introduce the role of type H vessels in the pathogenesis of OP and the regulation of miRNAs on type H vessel formation by affecting regulatory factors to provide some valuable insights for future studies of OP treatment.
Gut-bone axis research: unveiling the impact of gut microbiota on postmenopausal osteoporosis and osteoclasts through Mendelian randomization
Authors: Xiao Hefang , Wang Yaobin , Chen Yi , Chen Rongjin , Yang Chenhui , Geng Bin , Xia Yayi
Published: May 2024

Background

Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention.

Methods

We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287.

Results

The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis.

Conclusion

This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.
Effects of enclosure measures on soil water infiltration and evaporation in arid and semi-arid grassland in northern China
Authors: Fan Cairui , Guo Jinyan , Li Xiu , Zhang Chengfu , Wang Teng
Published: May 2024

Soil infiltration and evaporation are the main factors affecting the water cycle in arid and semi-arid areas, and the sealing measures determine the soil water storage capacity by affecting the evaporation and infiltration process of grassland soil water, which is the key to the ecological environment restoration of arid and semi-arid grassland. This study taking the enclosure time of Hulunbuir grassland for 3 years, 7 years, 10 years and the grazing control grassland as the research objects by using small evaporation instrument and double-ring infiltration instrument.To study the effects of enclosure measures on soil water distribution, soil infiltration and evaporation, and to evaluate the applicability of the main soil evaporation and infiltration models in enclosed grassland. The results show that (1) the enclosure measures can effectively improve the soil water content. In the vertical direction, the soil water content shows a trend of increasing first and then decreasing. (2) The initial infiltration rate and stable infiltration rate of grassland at different enclosure time are significantly different (P<0.05), and the soil infiltration rate and evaporation rate were in the order of EN10 >EN7 >EN3 >CK. (3) Using three infiltration process models to simulate the grassland infiltration process at different enclosure times, the Horton model is able to better model the inflection points of the infiltration process, and the fit accuracy is higher than that of the Philip and Kostiakov models. (4) The cumulative evaporation process of grassland at different closure times was simulated by using Black, Ross, and Power function models.The simulation values calculated by the Rose model are the closest to the measured value, and the simulation accuracy is the highest.The comprehensive analysis shows that the hydrological characteristics of grassland soil change significantly in the early stage of enclosure phase, and the soil properties have reached a good state for 3 to 7 years.With the continuous increase of enclosure time, the change of soil hydrological characteristics is not obvious. The results are helpful for soil and water conservation and ecological environment management in arid and semi-arid grassland.
Colour polymorphism of cotton bollworm larvae as a function of the type of host plant providing its development
Authors: Keszthelyi Sándor , Orsi-Gibicsár Szilvia , Pál-Fám Ferenc , Somfalvi-Tóth Katalin , Balog Adalbert
Published: May 2024

A well-known insect phenomenon is colour polymorphism, from which the species hopes to gain some ecological advantage. Herbivores adapt to the colours of their environment to reduce their chances of becoming prey, while predators use camouflage colours to succeed in hiding from prey. The larvae of the cosmopolitan, highly invasive cotton bollworm (Helicoverpa armigera Hbn., Lep.: Noctuidae) also benefit from this morphological polymorphism. Their fully-developed larvae can take on various colours when feeding on foliage. Our study aimed to determine the host plant-related colour adaptation of H. armigera larvae collected from different plant organs using different spectral analysis methods. Our studies, based on colour analysis of photographic images, showed that the colour of fully-developed larvae of the species is highly correlated with the colour of the damaged nutrient plant. The dominant colours of the larvae show a high similarity with the colours of the consumed host plant parts. The RGB-based analysis confirmed that larval colours are clustered according to the host plant’s organs and are mainly located in the yellow and green regions of the visible light spectrum. All these results confirm the extraordinary adaptive capabilities of this invasive species, which, among other things, verify its worldwide distribution.
Carbon storage and carbon pool characteristics of Larix gmelinii forest in Daxing’anling, Inner Mongolia, China
Authors: Zhao Kai , Yue Yongjie , Qin Fucang , Hai Long , Yi Lixi , Zhao Pengwu , Hao Longfei , Shu Yang , Zheng Yaxiong , Li Long , He Rong , Xu Yajie
Published: May 2024

Larix gmelinii is an important ecological construction tree species in northern China, and its carbon storage and distribution characteristics are of great significance for evaluating the carbon balance and climate effect of forest ecosystems. However, at present, there is a lack of systematic research on the carbon storage of L. gmelinii forests and its change with forest age. In this paper, the biomass and carbon density of L. gmelinii forests at different ages and the distribution of carbon storage in vegetation and soil were analyzed by means of sample plot investigation and model simulation in the northern forest area of Daxing’anling, Inner Mongolia. The influence of forest age on the carbon storage and carbon pool distribution characteristics of L. gmelinii forests and the mechanism of influencing factors were also discussed. Results show that: (1) As forest age increased, the total amount of carbon pools initially increased and then decreased, and the distribution structure of carbon pools showed a trend of transferring from soil to trees. The proportion of soil carbon pools gradually decreased (72.72–51.87%), while the proportion of tree carbon pools gradually increased (23.98–39.33%). The proportion of shrub and grass carbon pools was also relatively stable (0.51–0.53%). (2) Soil carbon pool was affected by the input and output of soil organic matter, soil depth, soil carbon content, and soil bulk density, shrub–grass carbon pool was affected by undergrowth light conditions and soil moisture, litter carbon pool was affected by litter input and output, and the carbon pool of trees was affected by the growth rate and carbon balance of trees. This study provides scientific basis and management suggestions for the carbon storage capacity of L. gmelinii forests and the mitigation of climate change.
Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism
Authors: Liu Baoyi , Li Ang , Liu Yi , Zhou Xinzhu , Xu Jingkai , Zuo Xianbo , Xue Ke , Cui Yong
Published: May 2024

Background

SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.

Methods

We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes.

Results

Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.

Conclusion

Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.
Expression and clinical significance of interleukin-6 pathway in cholangiocarcinoma
Authors: Gu Dongqing , Zhao Xin , Song Jing , Xiao Jianmei , Zhang Leida , Deng Guohong , Li Dajiang
Published: May 2024

Background

Cholangiocarcinoma (CCA) is a typical inflammation-induced malignancy, and elevated serum interleukin-6 (IL-6) levels have been reported to be linked to the onset and progression of CCA. We aim to investigate the potential prognostic value of the IL-6 pathway for CCA.

Methods

We detected the expressions of IL-6, IL-6R, glycoprotein (gp130), C-reactive protein (CRP), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) in CCA tissue microarray using multiplex immunofluorescence. Furthermore, the clinical associations and prognostic values were assessed. Finally, single-cell transcriptome analysis was performed to evaluate the expression level of IL-6 pathway genes in CCA.

Results

The results revealed that the expression of IL-6 was lower, while the expression of STAT3 was higher in tumor tissues compared to normal tissues. Especially in tumor microenvironment, the expression of IL-6 pathway genes was generally downregulated. Importantly, gp130 was strongly correlated with JAK2 in tumor tissues, while it was moderately correlated with JAK2 in normal tissue. Although none of the gene expressions were directly associated with overall survival and disease-free survival, our study found that IL-6, IL-6R, CRP, gp130, and JAK2 were inversely correlated with vascular invasion, which is a risk factor for poor prognosis in patients with CCA.

Conclusion

The findings from this study suggest that the IL-6 signaling pathway may have a potential prognostic value for CCA. Further investigation is needed to understand the underlying molecular mechanisms of the IL-6 pathway in CCA.
Characterization of anti-drug antibody responses to the T-cell engaging bispecific antibody cibisatamab to understand the impact on exposure
Authors: Lotz Gregor P. , Lutz Achim , Martin-Facklam Meret , Hansbauer Andre , Schick Eginhard , Moessner Ekkehard , Antony Michael , Stuchly Thomas , Viert Maria , Hosse Ralf J. , Freimoser-Grundschober Anne , Klein Christian , Schäfer Martin , Ritter Mirko , Stubenrauch Kay-Gunnar
Published: May 2024

An appropriately designed pharmacokinetic (PK) assay that is sensitive for anti-drug antibody (ADA) impact on relevant exposure is an alternative strategy to understand the neutralizing potential of ADAs. However, guidance on how to develop such PK assays and how to confirm the functional ADA impact on exposure is missing. Here, the PK assay of a T-cell-engaging bispecific antibody, cibisatamab, was developed based on its mechanism of action (MoA). Using critical monoclonal anti-idiotypic (anti-ID) antibody positive controls as ADA surrogates, the impact on exposure was evaluated pre-clinically. In a phase I clinical trial (NCT02324257), initial data suggest that the combination of ADA and PK assays for correlation of the ADA response with cibisatamab exposure. To understand the neutralizing potential of patient-derived ADAs on drug activity, advanced ADA characterization has been performed. Structural binding analysis of ADAs to antibody domains of the drug and its impact on targeting were assessed. For this purpose, relevant patient ADA binding features were identified and compared with the specific monoclonal anti-ID antibody-positive controls. Comparable results of target binding inhibition and similar impacts on exposure suggest that the observed reduction of Cmax and Ctrough levels in patients is caused by the neutralizing potential of ADAs and allows a correlation between ADA response and loss of exposure. Therefore, the described study provides important functional aspects for the development of an appropriately designed PK assay for bispecific antibodies as an alternative option towards understanding the neutralizing ADA impact on exposure.
Unveiling the multifaceted antitumor effects of interleukin 33
Authors: Arrizabalaga Leire , Risson Aline , Ezcurra-Hualde Miriam , Aranda Fernando , Berraondo Pedro
Published: May 2024

Interleukin 33 (IL-33), once predominantly recognized for its pro-tumoral activities, has emerged as a multifunctional cytokine with antitumor properties. IL-33 pleiotropic activities include activation of Th1 CD4+ T cells, CD8+ T cells, NK cells, dendritic cells, eosinophils, as well as type 2 innate lymphoid cells. Regarding this immunomodulatory activity, IL-33 demonstrates synergistic interactions with various cancer therapies, including immune checkpoint blockade and chemotherapy. Combinatorial treatments leveraging IL-33 exhibit enhanced antitumor efficacy across different tumor models, promising novel avenues for cancer therapy. Despite its antitumor effects, the complex interplay of IL-33 within the tumor microenvironment underscores the need for further investigation. Understanding the mechanisms underlying IL-33’s dual role as both a promoter and inhibitor of tumor progression is essential for refining therapeutic strategies and fully realizing its potential in cancer immunotherapy. This review delves into the intricate landscape of IL-33 effects within the tumor microenvironment, highlighting its pivotal role in orchestrating immune responses against cancer.
Isolation and characterization of probiotic Lysinibacillus species from the gastrointestinal tract of large yellow croaker (Larimichthys crocea)
Authors: Yao Yuxin , Wang Xi , Lin Xiangyang , Wu Jianshao , Wang Pan , Zhu Chuanzhong , Yan Qingpi
Published: May 2024

The objective of this study was to identify effective strategies for disease prevention and control that circumvent antimicrobial resistance (AMR) issues, thereby facilitating sustainable aquaculture practices. This research focused on isolating probiotic Bacillus strains from the intestinal tract of healthy large yellow croaker (Larimichthys crocea). Among the 11 strains tested, four demonstrated protease and lipase activities. Further testing identified one strain, Lysinibacillus sp. (LYD11), with strong inhibitory activity against Vibrio harveyi and Vibrio alginolyticus, two major pathogens of the large yellow croaker. The screened strains showed more than 45% co-aggregation with five pathogens and were capable of inhibiting pathogen colonization through competition, repulsion, and substitution adhesion of 20.56 to 48.45%, 40.37 to 75.62% and 55.51 to 85.30%, respectively. The hydrophobicity and self-aggregation rates of LYD11 were 82.73% and 49.47%, respectively, indicating a potent ability for adhesion and colonization within the fish intestine. LYD11 demonstrated robust growth under the NaCl 0.5–3.5% and pH range of 6–8 and was unaffected by the gastrointestinal environment. Safety evaluations at high concentrations in grouper, in both injected and fed groups, indicated no adverse effects, as evidenced by the absence of morbidity or mortality. Consequently, Lysinibacillus sp. LYD11 emerges as a potential probiotic candidate for the prevention and control of bacterial diseases in the large yellow croaker.