bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-1 single transcription start site mutants display complementary replication functions that are restored by reversion
Authors: GC K. , Lesko S. , Emery A. , Burnett C. , Gopal K. , Clark S. , Swanstrom R. , Sherer N.M. , Telesnitsky A. , Kharytonchyk S.
Published: December 2024

HIV-1 transcription initiates at two positions, generating RNAs with eithercap1G orcap3G 5′ ends. The replication fates of these RNAs differ, with viral particles encapsidating almost exclusivelycap1G RNAs andcap3G RNAs retained in cells where they are enriched on polysomes and among spliced viral RNAs. Here, we studied replication properties of virus promoter mutants that produced only one RNA 5′ isoform or the other: separately, in combination, and during spreading infection. Results showed that either single start RNA could serve as both mRNA and genomic RNA when present as the only form in cells, althoughcap3G RNA was more efficiently translated and spliced whilecap1G RNA was packaged into nascent virions slightly better than RNAs from the parental virus. When co-expressed from separate vectors,cap1G RNA was preferentially packaged into virions. During spreading infectioncap1G-only virus displayed only minor defects butcap3G-only virus showed severe replication delays in both the highly permissive MT-4 cell line and in primary human CD4+ T cells. Passage ofcap3G-only virus yielded revertants that replicated as well as the twinned (cap1G+cap3G) transcription start site parent. These revertants displayed restored packaging and splicing levels and had regained multiple transcription start site use.

Importance

HIV-1 generates two RNAs during its replication that differ by only two nucleotides in length. Despite this very minor difference, the RNAs perform different and complementary replication functions. When mutants that expressed only one RNA were forced to revert, they regained functions associated with the second RNA.
CGC1, a new reference genome forCaenorhabditis elegans
Authors: Ichikawa Kazuki , Shoura Massa J. , Artiles Karen L. , Jeong Dae-Eun , Owa Chie , Kobayashi Haruka , Suzuki Yoshihiko , Kanamori Manami , Toyoshima Yu , Iino Yuichi , Rougvie Ann E. , Wahba Lamia , Fire Andrew Z. , Schwarz Erich M. , Morishita Shinichi
Published: December 2024

The original 100.3 Mb reference genome forCaenorhabditis elegans, generated from the wild-type laboratory strain N2, has been crucial for analysis ofC. eleganssince 1998 and has been considered complete since 2005. Unexpectedly, this long-standing reference was shown to be incomplete in 2019 by a genome assembly from the N2-derived strain VC2010. Moreover, genetically divergent versions of N2 have arisen over decades of research and hindered reproducibility ofC. elegansgenetics and genomics. Here we provide a 106.4 Mb gap-free, telomere-to-telomere genome assembly ofC. elegans, generated from CGC1, an isogenic derivative of the N2 strain. We used improved long-read sequencing and manual assembly of 43 recalcitrant genomic regions to overcome deficiencies of prior N2 and VC2010 assemblies, and to assemble tandem repeat loci including a 772-kb sequence for the 45S rRNA genes. While many differences from earlier assemblies came from repeat regions, unique additions to the genome were also found. Of 19,972 protein-coding genes in the N2 assembly, 19,790 (99.1%) encode products that are unchanged in the CGC1 assembly. The CGC1 assembly also may encode 183 new protein-coding and 163 new ncRNA genes. CGC1 thus provides both a completely defined reference genome and corresponding isogenic wild-type strain forC. elegans, allowing unique opportunities for model and systems biology.
The Cardioprotective Effect of Ischemic Postconditioning is Mediated by Inhibiting RAP2C-MAP4K4 Pathway
Authors: Yan Peng , Yu Zaixin , Hu Zhiqiang , Li Sheng , Juaiti Muka Mengjiang , Zhang Min
Published: December 2024

Background

Ischemic postconditioning (PostC) serves as a vital defense for cardiomyocytes against the deleterious effects of ischemia/reperfusion (I/R) injury, the beneficial effects could be further enhanced through pharmacological strategies. Our prior research demonstrated upregulated expression of the GTP-binding protein RAP2C in H9C2 cells post hypoxia-reoxygenation (H/R). The cardioprotective effects of RAP2C and underlying mechanisms are unclear. We therefore explored the role of RAP2C in PostC-induced cardioprotection against I/R injury.

Methods

Open-chest rat I/R and primary cultured cardiomyocytes H/R models were used. RAP2C and MAP4K4 expression was detected by immunohistochemistry and Western blotting. The BioGRID and STRING databases were tapped to predict the RAP2C-MAP4K4 binding, which was confirmed by co-immunoprecipitation and immunofluorescence.

Results

Results indicated that I/R and H/R upregulated the protein levels of RAP2C, MAP4K4, phospho-JNK, phospho-P38, and phospho-ERK, concomitant with increased apoptosis. PostC mitigated these effects. The pro-apoptotic impacts and the activation of the MAPK pathway induced by H/R were attenuated by RAP2C knockdown and intensified by RAP2C overexpression. H/R increased the interaction between RAP2C and MAP4K4, and PostC attenuated this effect. MAP4K4 knockdown reduced the pro-apoptotic and MAPK-activating effects induced by both RAP2C overexpression and hypoxia/reoxygenation (H/R).

Conclusions

These results demonstrate that PostC reduces cardiomyocyte apoptosis via modulating RAP2C/MAP4K4 pathways, suggesting their potential as therapeutic targets for the treatment of ischemic heart disease.
Study of exclusive decays of
Bs→ψ(1S,2S)Ks
and
Bs→ηc(1S,2S)Ks
Authors: Nayak Lopamudra , Patnaik Sonali , Sadangi Priyanka , Swain Sanjay Kumar
Published: December 2024

We analyze the exclusive two-body nonleptonic decays of Bs meson to ground as well as radially excited 2S charmonium state with a light meson Ks, induced by the b→cc¯d transition. Within the framework of relativistic independent quark model based on a flavor-independent interaction potential in scalar-vector harmonic form, we calculate the weak form factors from the overlapping integrals of meson wave function obtained in this model. Using the factorization approximation, we predict the branching fractions for the Bs→ψ(1S,2S)Ks and Bs→ηc(1S,2S)Ks, which can be compared with future theoretical predictions. Branching fraction for Bs→J/ψKs decay is found to be in good agreement with the data from the LHCb collaboration, whereas for Bs→ψ(2S)Ks, it is found to be within the detection ability of the CMS collaboration. We also predict the ratios of branching fractions (R), which are in broad agreement with the data from LHCb collaboration. These results indicate that the present approach works well in the description of exclusive nonleptonic Bs decays within the framework of the relativistic independent quark model.

Published by the American Physical Society
2024
Running coupling for holographic QCD with heavy and light quarks: Isotropic case
Authors: Aref’eva Irina Ya. , Hajilou Ali , Slepov Pavel , Usova Marina
Published: December 2024

We consider the running coupling constant in holographic models supported by Einstein-dilaton-Maxwell action for heavy and light quarks. To obtain the dependence of the running coupling constant α on temperature and chemical potential we impose boundary conditions on the dilaton field that depend on the position of the horizon. We use two types of boundary conditions: a simple boundary condition with the dilaton field vanishing at the horizon and a boundary condition that ensures an agreement with lattice calculations of string tension between quarks at zero chemical potential. The location of the first order phase transitions in the (μ,T) plane does not depend on the dilaton boundary conditions for light and heavy quarks. At these phase transitions, the function α undergoes jumps depending on temperature and chemical potential. We also show that for the second boundary conditions the running coupling decreases with a temperature increase, and the dependence on temperature and chemical potential both for light and heavy quarks is actually specified in quark-gluon plasma (QGP) phase by functions of one variable, demonstrating in this sense automodel behavior.

Published by the American Physical Society
2024
Subdynamics in a many-body system of quantum particles
Authors: Los Victor F.
Published: December 2024

For a system of N≫1 spinless quantum particles, the projection operator is introduced, which, surprisingly, exactly transforms the inhomogeneous (with irrelevant initial correlations term) Nakajima-Zwanzig generalized master equation (GME) into completely closed (homogeneous) GME with initial correlations included into the kernel governing its evolution. The obtained equation is equivalent to the closed linear evolution equation for an S-particle (S<N) statistical operator, which holds for any initial condition and all timescales. Thus, the introduced projector implements the idea of the subdynamics in the subspace of S-particle complex. It also allows for precise treatment of the initial correlations on an equal footing with collisions. No “molecular chaos” -type approximation is used. The obtained homogeneous equation is further specialized in the linear approximation in the particles density n for the kernel and considered in detail for the one-particle statistical operator. The influence of both the quantum correlations, caused by the particles' statistics, and initial correlations, related to the interparticle interaction, is considered in detail and at different timescales. Connection of the linear equation for a one-particle statistical operator to the nonlinear quantum Boltzmann equation is shown.

Published by the American Physical Society
2024
The impacts of convergence policies on macroeconomic stability in the West African monetary zone
Authors: Abdul Rahman Yahuza , Osei-Fosu Anthony Kofi , Sakyi Daniel
Published: December 2024

Purpose

This paper examines the effectiveness of the joint impact of convergence policy measures on macroeconomic stability conditions in the West African monetary zone (WAMZ) countries, using an annual panel data from 1990 to 2021.

Design/methodology/approach

It uses the dynamic autoregressive distributed lag (ARDL) approach to exploit the short and long run dynamics macro stability. A composite convergence index was constructed and its impact was examined on three different macroeconomic stability measures representing: internal stability, external stability and overall stability.

Findings

Findings from the study suggest that a unit deviation of the convergence policy index from its mean, in the short run, leads to worsening external and overall macroeconomic stability conditions in the zone, but it leads to improvement in the internal macroeconomic stability conditions. However, in the long run, the opposite occurs, a unit deviation of the convergence policy index from its mean, it leads to improvement in both external and overall macroeconomic stability situations and deterioration in internal macroeconomic stability situation.

Practical implications

It is concluded that the convergence policy criteria are effective only in the long run and therefore these policies alone cannot be used to achieve short run macroeconomic stability within the zone. Thus, policymakers should have a second look at how fiscal and monetary policies are conducted and also work to address structural challenges.

Originality/value

The paper examines the effectiveness of the joint impact of convergence policy measures on macroeconomic stability conditions in the WAMZ countries.
Sustainability in Brazilian companies within ISE B3: an analysis based on multicriteria decision-making technique
Authors: Fernandes Yasmin Shawani , Ferrarese Pegino Paulo Marcelo , Contani Eduardo Augusto do Rosário , Fidelis Reginaldo
Published: December 2024

Purpose

This study proposes a method for analyzing the sustainability of companies according to the Corporate Sustainability Index (ISE B3) while considering environmental, social and governance (ESG) dimensions.

Design/methodology/approach

As a quantitative and descriptive work, our study is based on analyses of responses to ISE B3 questionnaires. We consider 12 scenarios involving the allocation of different weights to important ESG dimensions and use the TOPSIS multicriteria decision-making method to evaluate companies in Brazil.

Findings

The results provide empirical evidence on the importance of balanced approach among the ESG dimensions and reflect the need for regulations and incentives to promote balanced ESG practices. We also identify companies with consistently good sustainability practices, such as Natura, those that deliver poor performance, such as Iochpe-Maxion S.A. and Azul S.A.

Research limitations/implications

We contribute to the literature by integrating a multicriteria methodology into the assessment of corporate sustainability, demonstrating the effectiveness of TOPSIS in different scenarios. We emphasize the importance of balancing the ESG dimensions, and in doing so provide novel perspectives in research.

Practical implications

Our findings offer a practical framework for managers to evaluate and refine their ESG strategies by using benchmarks from industry leaders. Policymakers can use them to formulate regulations and incentives that promote balanced ESG practices.

Originality/value

Our work clarifies the application of TOPSIS to several ESG-based scenarios and presents a comprehensive strategy for evaluating corporate sustainability. Our model can be reproduced and customized in diverse settings and contributes to the literature on corporate sustainability.
Process reengineering and public value creation: using process mining in courts
Authors: Racis Serena , Spano Alessandro , Latti Giorgio
Published: December 2024

Purpose

This study aims to apply Process Mining (PM) techniques to identify the critical elements that primarily affect the trials’ duration and suggest the best practices to enable their more efficient execution, reduce their duration and, consequently, create public value, through a case study conducted in an Italian Civil Court.

Design/methodology/approach

Through PM analyses and in-depth discussions with the court staff, we analysed the trials with the longest duration and those belonging to a specific subject matter to identify peculiar features and inefficiencies that prolong the trials’ duration.

Findings

Our results highlight how innovative tools like PM can revolutionise the judicial system by providing judges with objective trials data that can support and facilitate the entire trials’ definition. However, many issues, especially related to the little spread data culture and process-oriented approach in courts, are highly present, leading to data inconsistencies and subsequent difficulties in trials’ analysis and interpretation.

Originality/value

Little research has devoted attention to the PM potential to enhance the judiciary. Our study contributes to this strand, yet adopting a different approach: it investigates the trials’ excessive length by focusing on bottlenecks and inefficient activities that slow down trials and identifies activities’ thresholds to monitor the trials’ execution and limit delays.
Transport sustainability – a bibliometric, systematic methodological review and future research opportunities
Authors: Tetteh Francis Kamewor , Owusu Kwateng Kwame , Mensah John
Published: December 2024

Purpose

Over the past decade, achieving sustainability in the transport sector has become a significant concern for governments and stakeholders. In this context, this study aims to comprehensively analyse the existing literature to document contributions and methodological deficiencies and pave the way for future research.

Design/methodology/approach

The authors used thematic, bibliometric and methodological systematic reviews of 39 articles across 30 sources from 112 authors between 2005 and 2023.

Findings

Using the Biblioshiny, the bibliometric analysis unveils the top prolific authors, contributing sources, most productive countries, top-cited papers and evolving keywords in advancing transport sustainability literature streams. The analyses revealed two strands of literature (those from the composite perspective and the triple-bottom-line perspective). The authors further consolidated indicators to measure the three pillars of transport sustainability comprehensively.

Originality/value

This paper uses a holistic approach to provide a state-of-the-art understanding of transport sustainability useful for the net zero or sustainable transport agenda. This paper is among the few attempts to consolidate indicators to measure transport sustainability from the triple bottom line perspective, whilst also offering exciting directions for future studies and inspiring hope for a more sustainable transport sector.
Researching Together: Researchers With and Without Disabilities Engage Across National and Interdisciplinary Boundaries
Authors: Mannion Jess , Vincent Lori B. , Kroeger Stephen D. , Blee Tricia , Daly Oisin , Gallagher Rhena , Higgins Bryan , McHugh Mairead , Wolfer Kerri , Hayes Brittany E.
Published: December 2024

Introduction

The Relationships and Sexuality Research Team consists of researchers with learning disabilities who specialise in research on sexual citizenship and use visual and creative research methods. They are collaborating with academics on an innovative, cross‐national, interdisciplinary and co‐produced research project that brings together research teams from Ireland, the United Kingdom and the United States. Together, we gauged how effective this way of working was for use with an international research team.

Methods

Each of the 10 researchers participated in an interview using graphic narrative to co‐create their story in comic form, uncover the origin stories and motivating elements of our mutual involvement and identify, in a formative way, conditions of equitable participation. Two focus groups followed this to explore perceptions and experiences of this project, one with the researchers with learning disabilities and one with the non‐disabled academics and practitioner‐researchers.

Results

Many benefits were identified. This approach fosters learning new perspectives and innovative research methods, leading to meaningful and equitable research outcomes. However, we identified various barriers relating to power and communication due to professional jargon, cultural terminology, speech and articulation differences, accents and online communication. This led us to devise several strategies to implement to work towards more inclusive research.

Conclusion

For research teams with diverse teams, there needs to be the opportunity to build trust and find common ground. Reflecting on the process and making changes early on is crucial, as well as focusing on inclusion and equity rather than agendas.
Design and Development of Novel Hybrids Based on Pyrrolo[2,1‐f][1,2,4]Triazine and 1‐(Methylpiperidin‐4‐yl) Aniline–Based Analogs: Exploring the Utility as Anticancer Agents via MERTK Inhibition
Authors: Sathe Balaji Dashrath , Jaiswal Shivani , Kumar Devendra , Singh Thakur Gurjeet , Nainwal Nidhi , Rawat Pramod , Yadav Savita , Kumar Bhupinder , Dwivedi Ashish Ranjan , Rathod S. V.
Published: December 2024

Mer‐tyrosine kinase (MERTK), a member of the AXL, TYRO3, and MERTK (TAM) family, is one of the promising targets for cancer treatment. It plays a key role in cancer cell survival and proliferation and regulates immune responses in cancer. The study aimed to rationally design and develop molecules considering the pharmacophoric requirements of MERTK using a multi‐synthetic approach followed by the hybridization of individual pharmacophores. A hybrid drug design approach was employed by hybridization of pyrrolo[2,1‐f][1,2,4]triazine and 1‐(methylpiperidin‐4‐yl)aniline pharmacophoric systems to develop novel leads (1K1–1K5). The molecules were synthesized via a multi‐step synthetic approach. The synthesized molecules were assessed for their pharmacological potential via cell viability, drug metabolism and pharmacokinetics (DMPK), and MERTK inhibition studies corroborated by in silico studies. IK5 was found to have an IC50 value of 0.36 μM towards A549, followed by 0.42 μM and 0.80 μM against MCF‐7 and MDA‐MB‐231 cells, respectively. Further, the molecules were also analyzed for their microsomal stability and were found to be stable with better intrinsic clearance profiles. The molecules thus pave a strategy for developing novel MERTK inhibitors and their advance in vitro and in vivo assessment in the future.
TRIM16 and PRC1 Are Involved in Pancreatic Cancer Progression and Targeted by Delphinidin
Authors: Wang Donghua , Lv Long , Du Jinghu , Tian Kui , Chen Yu , Chen Manyu
Published: December 2024

Pancreatic cancer (PC) is the leading cause of cancer‐related death worldwide, and new biomarkers, therapeutic targets, and candidate drugs are needed. In this work, three PC‐related microarray datasets (GSE183795, GSE28735, and GSE62452) were analyzed. The differentially expressed genes (DEGs) of PC were obtained with the limma package in R. Weighted gene co‐expression network analysis (WGCNA) and machine learning approaches were used to screen the hub genes. Kaplan–Meier plotter and receiver operating characteristic (ROC) curve analysis were utilized to assess the diagnostic efficacy of the hub genes. The binding ability between natural bioactive ingredients and hub proteins was evaluated by molecular docking and molecular dynamics simulation. CCK‐8, flow cytometry, transwell, and western blot assays were used to analyze the viability, apoptosis, cell cycle progression, invasion, and pathway change of PC cells. Additionally, a nude mice model was used to evaluate the aggressive properties of PC cells in vivo. In this study, a total of 988 DEGs were identified, which were mainly enriched in cell adhesion and PI3K‐Akt signaling pathway, and two core genes TRIM16 and PRC1 were further identified. The overall survival of patients with high expression of TRIM16 and PRC1 was shorter. Delphinidin (Del) had good binding affinity with both TRIM16 and PRC1, and Del could inhibit the viability, invasion, and metastasis of PC cells and induce cell apoptosis and G0/G1 phase arrest. In addition, Del could promote the activation of p53 and inhibit the activation of the PI3K/AKT signaling pathway in PC cells. In summary, TRIM16 and PRC1 are identified as prognostic biomarkers and therapeutic targets for PC, and Del has good binding affinity with them and may be a potential therapeutic agent for PC.
Coordination among cytoskeletal organization, cell contraction, and extracellular matrix development is dependent on LOX for aneurysm prevention
Authors: Aviram Rohtem , Zaffryar‐Eilot Shelly , Kaganovsky Anna , Odeh Anas , Melamed Shay , Militsin Ruslana , Coren Lavi , Pinnock Cameron B. , Shemesh Ariel , Palty Raz , Ganesh Santhi K. , Hasson Peleg
Published: December 2024

Distinct and seemingly independent cellular pathways affecting intracellular machinery or extracellular matrix (ECM) deposition and organization have been implicated in aneurysm formation. One of the key genes associated with this pathology in both humans and mice is lysyl oxidase (LOX), a secreted ECM‐modifying enzyme, highly expressed in medial vascular smooth muscle cells. To dissect the mechanisms leading to aneurysm development, we conditionally deleted Lox in smooth muscle cells. We find that cytoskeletal organization is lost following Lox deletion. Cell culture assays and in vivo analyses demonstrate a cell‐autonomous role for LOX affecting myosin light‐chain phosphorylation and cytoskeletal assembly resulting in irregular smooth muscle contraction. These results not only highlight new intracellular roles for LOX, but notably, they provide a link between multiple processes leading to aneurysm formation, suggesting LOX coordinates ECM development, cytoskeletal organization, and cell contraction required for media development and function.
Efficacy of a 3‐Month Oral Function Management Protocol Incorporating Provision of Dietary Advice for Older Outpatients: A Randomised Controlled Trial
Authors: Hori Ayaka , Ohta Midori , Horibe Yasuhiro , Ryu Masahiro , Ueda Takayuki
Published: December 2024

Objective

This study aimed to examine the effects of an oral hypofunction management protocol incorporating oral function training and provision of dietary advice for 3 months on the nutritional status and oral function of older patients diagnosed with oral hypofunction.

Background

Oral hypofunction is associated with poor nutritional status, emphasising the need for management protocols incorporating provision of nutritional guidance and dietary advice. However, the efficacy of such protocols remains unclear.

Materials and Methods

This quasi‐randomised controlled clinical trial included 80 patients (age ≥ 65 years) diagnosed with oral hypofunction who were divided into two groups (intervention and control). The intervention group was provided with dietary advice and instructed to perform daily oral function training. The patients' nutritional status and oral function were evaluated every 1.5 months. Intergroup and intragroup comparisons were made.

Results

The intervention group exhibited a significant increase in the mean Mini Nutritional Assessment score over the study period (baseline: 25.4 ± 3.2; after 3 months: 26.3 ± 3.0), whereas no significant difference was observed in the control group (baseline: 26.4 ± 2.4; after 3 months: 26.4 ± 2.7). The mean number of symptoms of poor oral function was 4.0 ± 1.0 and 3.9 ± 0.9 at baseline and 2.8 ± 1.3 and 3.0 ± 1.3 after 3 months in the intervention and control groups, respectively, with a significant difference within the groups.

Conclusion

Management protocols incorporating provision of nutritional advice effectively improved the oral function and nutritional status of older patients with oral hypofunction.
Integrative Genomic and Transcriptomic Analysis in Acute Interstitial Pneumonia
Authors: Kwak Donghee , Kang Junho , Yu Yeuni , Lee Hansong , Kim Yeongjoo , Kwon Eun Jung , Lim Dong Min , Mun Seongik , Kim Hyo Min , Lee Hae Seul , Kim Yun Hak , Yeo Hye Ju , Cho Woo Hyun
Published: December 2024

Acute Interstitial Pneumonia (AIP) represents a severe form of diffuse lung injury within the idiopathic interstitial pneumonia spectrum. Given the limited understanding of its molecular basis, this study aims to elucidate AIP's genomic and transcriptomic profiles to uncover its pathophysiological underpinnings and identify potential therapeutic targets. We conducted a comprehensive analysis of genomic and transcriptomic data from lung tissues of 15 AIP patients. This included assessing differentially expressed genes (DEGs) and identifying mutations in exonic coding variants, as well as analysing expression quantitative trait loci (eQTL) profiles to link non‐coding SNP genotypes with gene expression levels. Transcriptomic analysis revealed a significant upregulation of genes linked to the Type I interferon receptor and keratin filament, and a downregulation of genes related to focal adhesion and endothelial integrity, compared to healthy individuals. These patterns were distinct from those observed in idiopathic pulmonary fibrosis (IPF) and non‐IPF interstitial lung diseases (ILDs). Genomic analysis highlighted mutations in genes associated with keratin and the extracellular matrix. Additionally, eQTL profiling provided insights into the genetic regulation of gene expression in AIP. Our findings reveals AIP's unique molecular landscape, differentiating it from other ILDs and laying the groundwork for future diagnostic and therapeutic research.
Hypoglycemic Agents Increase Regulatory Factor X1 to Inhibit Cancer Cell Behaviour in Human Glioblastoma Cells
Authors: Shan Weiran , Zuo Kendrick , Zuo Zhiyi
Published: December 2024

Glioblastoma multiforme is a deadly brain tumour in humans. We have shown that regulatory factor X1 (RFX1), a transcription factor, inhibits the proliferation, migration and invasion of human glioblastoma cells. This study was designed to identify the existing medications that could increase RFX1 in human glioblastoma cells and to determine whether these medications could inhibit the cancer cell behaviours. A bioinformatics approach was used to identify the medications that increased RFX1. The effects of these medications on human glioblastoma cell proliferation, migration and invasion were assayed under cell culture and mouse brain xenograft conditions. Pioglitazone, rosiglitazone and WY‐14643 increased RFX1 based on bioinformatics prediction and Western blotting data. These hypoglycemic agents reduced the proliferation, migration and invasion of human glioblastoma cell cultures. These agents reduced metalloproteinase 2 (MMP2) activity in the culture medium. Silencing RFX1 attenuated hypoglycemic agent‐induced inhibition of cancer cell behaviours and MMP2 activity. Pioglitazone reduced the xenograft tumour volume and migration distance of U87 human glioblastoma cells in the mouse brain. RFX1‐siRNA attenuated these effects. Our results provide additional evidence for RFX1 as a therapeutic target for human glioblastoma and suggest that pioglitazone, rosiglitazone and WY‐14643 inhibit cancer cell behaviour of human glioblastoma cells via upregulating RFX1.
Beetroot Microgreens (Beta vulgaris) Powder Obtained by Cast‐Tape Drying and Freeze‐Drying
Authors: Freitas Guilherme Meira , Cicotti Lurian , Constant Patrícia Beltrao Lessa , Zotarelli Marta Fernanda , de Sá João Paulo Natalino , Mazzutti Simone , de Oliveira Frederico Alberto , Durigon Angelise
Published: December 2024

The study aimed to dehydrate beet microgreen foams using cast‐tape drying and freeze‐drying to obtain powder and characterize them in terms of physicochemical properties and betalain. Foam formulations were analyzed: F1 = 78.3% water + 13% microgreens + 6.5% Emustab + 2.2% pre‐gelatinized starch; F2 = 78.3% water + 13% microgreens + 4.4% pre‐gelatinized starch + 4.3% Emustab. The formulated foams were dried using cast‐tape drying (CTD) (70°C and 2 mm spreading thickness) and freeze‐dried (FD). The drying time for CTD was 12 min for CTDF1 and 24 min for CTDF2 (moisture of 0.1 g/g). The FD time was 14 h for FDF1 and 18 h for FDF2 (moisture of 0.02 g/g). The water activity and moisture content of the powder obtained by CTD were lower than that of the FD powder for both formulations, and the protein content in F2 (4%–4.6%) was lower than in F1 (5.2%–6.3%). The foam allows for the rapid drying of beet microgreens by CTD due to the high drying rate and moderate temperature. The CTDF2 powder has lower moisture and activity water, violet/red coloration, good flowability, and low cohesiveness compared to the other samples. Freeze‐drying shows higher betalain retention (FDF1). Microgreens in powdered form constitute viable protein sources to be incorporated into plant‐based products, while betalain allows using this powder as a natural dye. These potential applications demand further investigation, aiming at a potential introduction as a new product in the market.
Genome‐wide identification and characterization of potato NRL gene family and functional analysis of StNRL‐6 in response to Phytophthora infestans
Authors: Cheng Dong , Qiu Huishan , Zhou Dan , Lin Tianyu , Liu Lang , Nie Jiahui , He Qin , Tian Zhendong
Published: December 2024

NPH3/RPT2‐Like (NRL) proteins, as blue light receptor phototropin‐interacting modules, regulate various aspects of physiological responses in light signaling. However, little information is available on NRL family members regulating plant immunity, especially concerning plants' late blight resistance to Phytophthora infestans. In this study, a systematical analysis of the potato NRL family was performed. In total, 35 StNRL genes were identified and phylogenetically classified into six subfamilies. Twelve StNRL genes were defined as seven pairs of segmental duplication, which was the major evolutionary driving force for StNRL expansion. Synteny analysis between the genomes of potato and Arabidopsis thaliana, tomato, and rice provided insights into evolutionary characteristics. Two StNRL family members, StNRL‐6 and StNRL‐7, interacted with the blue light photoreceptor Stphot1 and negatively regulated potato and Nicotiana benthamiana resistance against P. infestans. Moreover, the key motif RxSxS identified in the NRL family member is essential for StNRL‐6 to interact with Stphot1 and enhance plant susceptibility to P. infestans. This comprehensive analysis of the StNRL family provides valuable information to elucidate key molecular mechanisms on how blue light regulates plant immunity.
Litigation as a Governance Strategy: Courts, Bureaucracies and the Welfare Rights of Irregular Migrants
Authors: Andreetta Sophie
Published: December 2024

Over the last few years, the welfare rights of illegalized migrants living in Belgium have become increasingly restricted. Without a legal residence status, such rights are limited to (conditional) access to public healthcare. Welfare courts have, however, sometimes gone against the grain and granted social assistance benefits to irregularized applicants, based on fundamental rights principles. Conflicting jurisprudential trends have emerged and are still debating the ambiguous, and multiple meanings of ‘human dignity’ especially for those with a precarious immigration status. This article delves into the role of courts in the implementation of migrants' welfare rights. Based on ethnographic fieldwork within welfare courts, in public administrations and amongst migrants, it shows how litigation has become part of the daily governance of social protection. This allows certain categories of migrants to gain access to financial assistance, yet creates lengthy, complex procedures and leading to great uncertainty for claimants.
Variegated digital state repression in Central Asia
Authors: Knox Colin , Kurmanov Bakhytzhan
Published: December 2024

Existing research on digital activism in autocratic regimes tends to treat Central Asia as a homogenous entity with similar approaches to how new digital technologies are used for the purposes of state repression. Drawing on Feldstein's taxonomy of digital repression and new empirical evidence, this essay shows that digital state repression varies across the region. The presented findings add to current scholarship in three ways. First, we consider different forms of autocracies within Central Asia as a differentiated geography. Second, we examine the factors which led to a shift in how technologies could be used by autocracies as policy instruments to control their citizens. Third, given the growth of technological innovations that can sustain autocracies, we examine the specific mix of technologies within the different types of autocracies that shape the strategies of repression in Central Asia. The research presents a variegated picture of digitally‐enabled deepening autocratization in Central Asia.
Identification of the Novel HLA‐DPB1*03:01:27 Allele by Next‐Generation Sequencing
Authors: Muniyappa Nagesh , Pati Priti Priyadarsini , Pitale Jayee , Phalke Sameer , Pandey Rajeev Kumar
Published: December 2024

The novel HLA‐DPB1*03:01:27 allele differs from HLA‐DPB1*03:01:01 by one nucleotide substitution in codon 199 exon 4.
The Full‐Length Genomic Sequence of the HLA‐B*40:298:02 Allele
Authors: Tian Wei , Li LiXin
Published: December 2024

HLA‐B*40:298:02 differs from HLA‐B*40:01:01 by eight nucleotide positions residing in exon 1 to intron 6.
La libertad de Reinaldo Arenas. Un estudio de su obra poética
Authors: Pérez José Ángel
Published: December 2024

Este ensayo analiza la concepción de la libertad en la obra poética de Reinaldo Arenas. Atiende a motivos como la esclavitud, la exclusión y la muerte para comprender el mundo coaccionario que este autor presenta; así como los modos en que se realiza en ese mundo la libertad, mediante motivos que van desde suicidio hasta la creación artística. Se construye como resultado un mapa de los motivos poéticos mediante los que se muestra la concepción de la libertad implícita en su poesía.
Ecological erosion and expanding extinction risk of sharks and rays
Authors: Dulvy Nicholas K. , Pacoureau Nathan , Matsushiba Jay H. , Yan Helen F. , VanderWright Wade J. , Rigby Cassandra L. , Finucci Brittany , Sherman C. Samantha , Jabado Rima W. , Carlson John K. , Pollom Riley A. , Charvet Patricia , Pollock Caroline M. , Hilton-Taylor Craig , Simpfendorfer Colin A.
Published: December 2024

The true state of ocean biodiversity is difficult to assess, and there are few global indicators to track the primary threat of overfishing. We calculated a 50-year Red List Index of extinction risk and ecological function for 1199 sharks and rays and found that since 1970, overfishing has halved their populations and their Red List Index has worsened by 19%. Overfishing the largest species in nearshore and pelagic habitats risks loss of ecomorphotypes and a 5 to 22% erosion of functional diversity. Extinction risk is higher in countries with large human coastal populations but lower in nations with stronger governance, larger economies, and greater beneficial fisheries subsidies. Restricting fishing (including incidental catch) and trade to sustainable levels combined with prohibiting retention of highly threatened species can avert further depletion, widespread loss of population connectivity, and top-down predator control.
A conserved bacterial genetic basis for commensal-host specificity
Authors: Gutiérrez-García Karina , Aumiller Kevin , Dodge Ren , Obadia Benjamin , Deng Ann , Agrawal Sneha , Yuan Xincheng , Wolff Richard , Zhu Haolong , Hsia Ru-Ching , Garud Nandita , Ludington William B.
Published: December 2024

Animals selectively acquire specific symbiotic gut bacteria from their environments that aid host fitness. To colonize, a symbiont must locate its niche and sustain growth within the gut. Adhesins are bacterial cell surface proteins that facilitate attachment to host tissues and are often virulence factors for opportunistic pathogens. However, the attachments are often transient and nonspecific, and additional mechanisms are required to sustain infection. In this work, we use live imaging of individual symbiotic bacterial cells colonizing the gut of living
Drosophila melanogaster
to show that
Lactiplantibacillus plantarum
specifically recognizes the fruit fly foregut as a distinct physical niche.
L. plantarum
establishes stably within its niche through host-specific adhesins encoded by genes carried on a colonization island. The adhesin binding domains are conserved throughout the Lactobacillales, and the island also encodes a secretion system widely conserved among commensal and pathogenic bacteria.
Room-temperature exceptional plasticity in defective Bi
2
Te
3
-based bulk thermoelectric crystals
Authors: Deng Tingting , Gao Zhiqiang , Li Ze , Qiu Pengfei , Li Zhi , Yuan Xinjie , Ming Chen , Wei Tian-Ran , Chen Lidong , Shi Xun
Published: December 2024

The recently discovered metal-like room-temperature plasticity in inorganic semiconductors reshapes our knowledge of the physical properties of materials, giving birth to a series of new-concept functional materials. However, current room-temperature plastic inorganic semiconductors are still very rare, and their performance is inferior to that of classic brittle semiconductors. Taking classic bismuth telluride (Bi
2
Te
3
)–based thermoelectric semiconductors as an example, we show that antisite defects can lead to high-density, diverse microstructures that substantially affect mechanical properties and thus successfully transform these bulk semiconductors from brittle to plastic, leading to a high figure of merit of up to 1.05 at 300 kelvin compared with other plastic semiconductors, similar to the best brittle semiconductors. We provide an effective strategy to plastify brittle semiconductors to display good plasticity and excellent functionality simultaneously.
Lessons learnt in the end-of-life management of a hospice inpatient with advanced oropharyngeal cancer established on clozapine for treatment-resistant schizophrenia
Authors: Williams Tegen , Rea Emily
Published: December 2024

Clozapine is a tightly controlled medication used effectively as a last-line agent in treatment-resistant schizophrenia, with a relatively narrow therapeutic window and significant interactions. Both underdosing and toxicity can be catastrophic to the patient. Patients with complex mental health illnesses are more at risk of head and neck cancers due to the high prevalence of associated risk factors including smoking, diet and alcohol. These patients also face barriers to accessing and using healthcare and may not tolerate procedures for artificial routes for feeding and medications. As the disease progresses, these patients are vulnerable to clozapine toxicity from factors such as constipation, reduction in cigarette smoking, weight loss and medication interactions. Conversely, they also risk underdosing with a relapse of distressing psychotic symptoms as the swallow deteriorates. This case highlights the need for considerate planning, prescribing, close monitoring and awareness alongside the importance of multidisciplinary working when caring for this patient group.
Natural lung-tropic TH9 cells: a sharp weapon for established lung metastases
Authors: Chen Tao , Qiao Chenxiao , Yinwang Eloy , Wang Shengdong , Wen Xuehuan , Feng Yixuan , Jin Xiangang , Li Shuming , Xue Yucheng , Zhou Hao , Zhang Wenkan , Zeng Xianchang , Wang Zenan , Sun Hangxiang , Jiang Lifeng , Li Hengyuan , Li Binghao , Cai Zhijian , Ye Zhaoming , Lin Nong
Published: December 2024

Background

Lung metastasis remains the primary cause of tumor-related mortality, with limited treatment options and unsatisfactory efficacy. In preclinical studies, T helper 9 (TH9) cells have shown promise in treating solid tumors. However, it is unclear whether TH9 cells can tackle more challenging situations, such as established lung metastases. Moreover, comprehensive exploration into the nuanced biological attributes of TH9 cells is imperative to further unravel their therapeutic potential.

Methods

We adoptively transferred TH1, TH9, and TH17 cells into subcutaneous,in situ, and established lung metastases models of osteosarcoma and triple-negative breast cancer, respectively, comparing their therapeutic efficacy within each distinct model. We employed flow cytometry and anin vivoimaging system to evaluate the accumulation patterns of TH1, TH9, and TH17 cells in the lungs after transfusion. We conducted bulk RNA sequencing onin vitrodifferentiated TH9 cells to elucidate the chemokine receptor CXCR4, which governs their heightened pulmonary tropism relative to TH1 and TH17 cell counterparts. Using Cd4creCxcr4flox/floxmice, we investigate the effects of CXCR4 on the lung tropism of TH9 cells. We performed mass spectrometry to identify the E3 ligase responsible for CXCR4 ubiquitination and elucidated the mechanism governing CXCR4 expression within TH9 cellular milieu. Ultimately, we analyzed the tumor immune composition after TH9 cell transfusion and evaluated the therapeutic efficacy of adjunctive anti-programmed cell death protein-1 (PD-1) therapy in conjunction with TH9 cells.

Results

In this study, we provide evidence that TH9 cells exhibit higher lung tropism than TH1 and TH17 cells, thereby exhibiting exceptional efficacy in combating established lung metastases. CXCR4-CXCL12 axis is responsible for lung tropism of TH9 cells as ablating CXCR4 in CD4+T cells reverses their lung accumulation. Mechanistically, tumor necrosis factor receptor-associated factor 6 (TRAF6)-driven hyperactivation of NF-κB signaling in TH9 cells inhibited ITCH-mediated ubiquitination of CXCR4, resulting in increased CXCR4 accumulation and enhanced lung tropism of TH9 cells. Besides, TH9 cells’ transfusion significantly improved the immunosuppressed microenvironment. TH9 cells and anti-PD-1 exhibit synergistic effects in tumor control.

Conclusions

Our findings emphasized the innate lung tropism of TH9 cells driven by the activation of TRAF6, which supports the potential of TH9 cells as a promising therapy for established lung metastases.
Magnetized nanofluid flowing across an inclined microchannel with heat source/sink and temperature jump: Corcione’s model aspects
Authors: Ramesh G. K. , Madhukesh J. K. , Hiremath Pradeep N. , Aly Emad H.
Published: December 2024

This paper focuses on applying the Corcione model to the microchannel. The Corcione model is highly relevant because it provides accurate empirical relationships for forecasting the dynamic viscosity and effective thermal conductivity of nanofluids. These qualities are crucial for building and improving different thermal systems. The model presents and discusses two simple empirical correlating equations for forecasting the dynamic viscosity and effective thermal conductivity of nanofluids. Hence the aim of this work is to use Corcione’s model to demonstrate the fully developed laminar flow of an electrically conducting nanoliquid through an inclined microchannel. The energy equation takes into account the physical impacts of the heat source/sink, temperature jamp, and viscous dissipation. TiO2 nanoparticles in water are taken into consideration in this work for enhanced cooling. Using the numerical program Maple, Runge–Kutta–Fehlberg 4th–5th-order method is utilized to solve the present research. Making use of graphs, all of the flow parameters are shown, and the physical consequences on the flow and temperature profiles are thoroughly examined. It is noted that a higher inclined angle enhances the velocity profile whereas a larger temperature jump declines the temperature profile. Furthermore, Corcione’s model often has greater velocities, temperatures, and reduced surface drag forces than the Tiwari–Das model.
Effect of Carbon Morphology and Slurry Formulation in Sulfur Cathode for Li-S Batteries
Authors: Lateef Saheed A. , Raulo Avinash , Chmiola John , Mustain William E. , Albano Fabio , Jalilvand Golareh
Published: December 2024

The performance of Lithium-Sulfur (Li-S) batteries is significantly influenced by material selection and manufacturing processes, with conductive carbon and slurry formulation playing crucial roles. In this study, the impact of carbon morphology and solvent/solid ratio in slurry preparation on microstructure and electrochemical performance of sulfur cathodes was investigated. Various carbon structures, such as nanotubes, sheets, and particles, were explored, and the solvent volume was adjusted to assess their effects on electrode architecture and electrochemical performance. Our findings demonstrate that the binder dissolution process and consequent electrode architecture and performance are highly influenced by both the carbon structure and slurry solvent volume. Furthermore, it was observed that, contrary to common assumption, advanced carbon structures are not necessary for enhanced capacity and durability of Li-S cathodes. Accordingly, the best cycling durability was achieved by optimizing the slurry with 300 μL/mgPVDF of NMP solvent and using Ketjen black as the conductive carbon, resulting in an initial capacity of 1029 mAh gS
−1, with a retention of 830 mAh gS
−1 after 500 cycles. These results, obtained at a high areal loading of 4.5 mgS cm−2, demonstrate the commercial potential of the proposed electrode formulation and processing method without reliance on advanced materials or techniques.