bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Coordinated Action of DesK/DesR and YvfT/YvfU to Control the Expression of an ABC Transporter in Bacillus subtilis
Authors: Fernández Pilar , Porrini Lucía , Pereyra Julián Ignacio , Albanesi Daniela , Mansilla María Cecilia
Published: September 2024

Two‐component systems (TCSs) are vital signal transduction pathways ubiquitous among bacteria, facilitating their responses to diverse environmental stimuli. In Bacillus subtilis, the DesK histidine kinase thermosensor, together with the response regulator DesR, constitute a TCS dedicated to membrane lipid homeostasis maintenance. This TCS orchestrates the transcriptional regulation of the des gene, encoding the sole desaturase in these bacteria, Δ5‐Des. Additionally, B. subtilis possesses a paralog TCS, YvfT/YvfU, with unknown target gene(s). In this work, we show that YvfT/YvfU controls the expression of the yvfRS operon that codes for an ABC transporter. Interestingly, we found that this regulation also involves the action of DesK/DesR. Notably, opposite to des, yvfRS transcription is induced at 37°C and not at 25°C. Our in vivo and in vitro experiments demonstrate that both YvfU and DesR directly bind to the operon promoter region, with DesR exerting its control over yvfRS expression in its unphosphorylated state. Our study uncovers an intriguing case of cross‐regulation where two homologous TCSs interact closely to finely tune gene expression in response to environmental cues. These findings shed light on the complexity of bacterial signal transduction systems and their critical role in bacterial adaptability.
Peptidoglycan Endopeptidase PBP7 Facilitates the Recruitment of FtsN to the Divisome and Promotes Peptidoglycan Synthesis in Escherichia coli
Authors: Liu Xinwei , Boelter Gabriela , Vollmer Waldemar , Banzhaf Manuel , den Blaauwen Tanneke
Published: September 2024

Escherichia coli has many periplasmic hydrolases to degrade and modify peptidoglycan (PG). However, the redundancy of eight PG endopeptidases makes it challenging to define specific roles to individual enzymes. Therefore, the cellular role of PBP7 (encoded by pbpG) is not clearly defined. In this work, we show that PBP7 localizes in the lateral cell envelope and at midcell. The C‐terminal α‐helix of PBP7 is crucial for midcell localization but not for its activity, which is dispensable for this localization. Additionally, midcell localization of PBP7 relies on the assembly of FtsZ up to FtsN in the divisome, and on the activity of PBP3. PBP7 was found to affect the assembly timing of FtsZ and FtsN in the divisome. The absence of PBP7 slows down the assembly of FtsN at midcell. The ΔpbpG mutant exhibited a weaker incorporation of the fluorescent D‐amino acid HADA, reporting on transpeptidase activity, compared to wild‐type cells. This could indicate reduced PG synthesis at the septum of the ΔpbpG strain, explaining the slower accumulation of FtsN and suggesting that endopeptidase‐mediated PG cleavage may be a rate‐limiting step for septal PG synthesis.
How to engineer a habitable planet: the rise of marine ecosystem engineers through the Phanerozoic
Authors: Cribb Alison T. , Darroch Simon A. F.
Published: September 2024

Ecosystem engineers are organisms that modify their physical habitats in a way that alters resource availability and the structure of the communities they live in. The evolution of ecosystem engineers over the course of Earth history has thus been suggested to have been a driver of macroevolutionary and macroecological changes that are observed in the fossil record. However, the rise to dominance of ecosystem engineers has not been thoroughly reconstructed. Here, we investigate the history of bioturbation and reef‐building (two of the most important marine ecosystem engineering behaviours today) over the Phanerozoic. Using fossil occurrences from the Paleobiology Database, we reconstruct how common communities influenced by ecosystem engineers were in the oceans, how dominant ecosystem engineers were within their own communities, and the taxonomic and ecological composition of bioturbators and reef‐builders. We find that bioturbation has become an increasingly common ecosystem engineering behaviour over the Phanerozoic, while reef‐building ecosystem engineers have not become more dominant since their Devonian apex. We also identify unique bioturbation and reef‐building regimes that are characterized by different ecosystem engineering taxonomic groups, ecological modes, and dominance, suggesting that the nature of ecosystem engineering has at times rapidly shifted over the course of the Phanerozoic. These reconstructions will serve as important data for understanding how ecosystem engineers have driven changes in biodiversity and ecosystem structure over the course of Earth history.
“No One Seems to See Us, and They Look at Us as Worthless Colleagues”: Challenges Experienced by Iranian Transplant Nurse Coordinators—A Qualitative Study
Authors: Mollazadeh Farzin , Habibzadeh Hossein , Parizad Naser
Published: September 2024

Background

Transplant nurse coordinators have close and long‐term interactions with organ donor families throughout the organ donation process. Due to the responsibilities and high sensitivity of organ transplant coordination, transplant nurse coordinators face several stressful challenges. This study aimed to explore the challenges faced by Iranian transplant nurse coordinators.

Methods

This is a qualitative study conducted using qualitative content analysis. This study was conducted from February to September 2023. Semi‐structured face‐to‐face interviews were conducted with a total of 14 transplant nurse coordinators. Data were analyzed using conventional qualitative content analysis proposed by Graneheim and Lundman.

Results

“Challenges of living as a transplant nurse coordinator” was identified as the main category, the subcategories of which included “consent‐obtaining obstacles,” “exposure to violence,” “compassion fatigue,” “obsessive thoughts,” “work–life imbalance,” and “hardworking coordinators in the shadow.”

Conclusions

The challenges experienced by transplant nurse coordinators can lead to several negative consequences, including job burnout and turnover, reduced quality of family and marital life, additional healthcare costs, and reduced organ donation rate. To address these challenges, cultivating a culture of organ donation in society could involve public awareness campaigns and educational initiatives. Improving the working conditions and occupational incentives could include reducing work hours, providing psychological support, and increasing salaries. Implementing psychological interventions could involve regular counseling sessions and stress management programs. These measures can effectively reduce the challenges transplant nurse coordinators face and improve their overall well‐being and job satisfaction.
Epistemic normativity without epistemic teleology
Authors: Kiesewetter Benjamin
Published: September 2024

This article is concerned with a puzzle that arises from three initially plausible assumptions that form an inconsistent triad: (i) Epistemic reasons are normative reasons (normativism); (ii) reasons are normative only if conformity with them is good (the reasons/value‐link); (iii) conformity with epistemic reasons need not be good (the nihilist assumption). I start by defending the reasons/value‐link, arguing that normativists need to reject the nihilist assumption. I then argue that the most familiar view that denies the nihilist assumption—epistemic teleology—is untenable. Finally, I consider two alternative ways of accounting for the goodness of conformity with epistemic reasons: it may be good because it accords with the virtue of reasons‐responsiveness, and it may be good because it is good to conform with normative reasons as such. I argue that both of these conceptions avoid the problems of epistemic teleology and merit serious consideration as potential solutions to the puzzle.
The role of target populations in resident support for local collaboration
Authors: Kalesnikaite Vaiva , Neshkova Milena I. , Porumbescu Gregory A.
Published: September 2024

The characteristics of populations benefiting from collaboration are mostly regarded as contextual factors in collaborative theory and research. Drawing on policy design and distributive justice theories, this study seeks to understand how public support for collaboration varies depending on the characteristics of the target population that benefits from collective action. The analysis demonstrates that collaborative arrangements aiding populations considered deserving are more likely to gain public approval than those benefiting negatively constructed groups. We also investigate citizens' attribution of blame for collaboration failure and find that the process appears to be independent of the characteristics of target populations.
Functional characterisation of BnaA02.TOP1α and BnaC02.TOP1α involved in true leaf biomass accumulation in Brassica napus L.
Authors: Peng Danshuai , Guo Yuan , Hu Huan , Wang Xin , He Shuangcheng , Gao Chenhao , Liu Zijin , Chen Mingxun
Published: September 2024

Leaves, as primary photosynthetic organs essential for high crop yield and quality, have attracted significant attention. The functions of DNA topoisomerase 1α (TOP1α) in various biological processes, including leaf development, in Brassica napus remain unknown. Here, four paralogs of BnaTOP1α, namely BnaA01.TOP1α, BnaA02.TOP1α, BnaC01.TOP1α and BnaC02.TOP1α, were identified and cloned in the B. napus inbred line ‘K407’. Expression pattern analysis revealed that BnaA02.TOP1α and BnaC02.TOP1α, but not BnaA01.TOP1α and BnaC01.TOP1α, were persistently and highly expressed in B. napus true leaves. Preliminary analysis in Arabidopsis thaliana revealed that BnaA02.TOP1α and BnaC02.TOP1α paralogs, but not BnaA01.TOP1α and BnaC01.TOP1α, performed biological functions. Targeted mutations of four BnaTOP1α paralogs in B. napus using the CRISPR‐Cas9 system revealed that BnaA02.TOP1α and BnaC02.TOP1α served as functional paralogs and redundantly promoted true leaf number and size, thereby promoting true leaf biomass accumulation. Moreover, BnaA02.TOP1α modulated the levels of endogenous gibberellins, cytokinins and auxins by indirectly regulating several genes related to their metabolism processes. BnaA02.TOP1α directly activated BnaA03.CCS52A2 and BnaC09.AN3 by facilitating the recruitment of RNA polymerase II and modulating H3K27me3, H3K36me2 and H3K36me3 levels at these loci and indirectly activated the BnaA08.PARL1 expression, thereby positively controlling the true leaf size in B. napus. Additionally, BnaA02.TOP1α indirectly activated the BnaA07.PIN1 expression to positively regulate the true leaf number. These results reveal the important functions of BnaTOP1α and provide insights into the regulatory network controlling true leaf biomass accumulation in B. napus.
Brussel in een België met vier Gewesten?
Authors: Moors Dirk , Vandenbroucke Anneloes , Degryse Iadine , Boone Simon
Published: September 2024

Bij eerdere staatshervormingen leken de scenario’s op afspraken van een scheidend echtpaar (Vlaanderen en Wallonië) dat het wel eens geraakt over de verdeling van hun gemeenschappelijke bezittingen, maar niet over Brussel. Hoewel het Brussels Gewest autonomie kreeg over de Gewestbevoegdheden, bleven de Brusselaars voor de Gemeenschapsbevoegdheden onder voogdij van de Gemeenschappen. Om de mening van de Brusselaars werd niet gevraagd. Het Brussels Studies Institute wil deze aanpak omdraaien en het institutionele debat benaderen vanuit het perspectief van Brussel, en van zijn inwoners. In dit boek buigen ruim vijfentwintig onderzoekers zich over de bevoegdheden die Brussel en de Brusselaars nodig hebben. Ze vertrekken hierbij vanuit het meest eenvoudige scenario: Brussel als autonoom gewest, zoals Vlaanderen en Wallonië, zonder onderscheid tussen gewest- en gemeenschapsbevoegdheden. Zou dit het leven van de Brusselaars verbeteren?
Cooling System of a High-Pressure Centrifugal Compressor: Development and Impact on Wheel Temperatures
Authors: Weihard Stefan , Willeke Tobias , Božek Lukáš , Hort Vladimír , Münch Stefan , Spengler Sebastian , Winter Thomas
Published: September 2024

High power density, low fuel consumption, and a compact design with competitive total costs of ownership are key requirements for internal combustion engines for conventional fuels and carbon-free or carbon-neutral future fuels. These requirements influence the development targets of charging systems and call for single-stage charging systems with increased charge air pressures. However, high compressor pressure ratios of the turbocharger lead to challenging material temperatures in aluminum alloy wheels. Consequently, creep becomes the fundamental lifetime-limiting damage mechanism for these wheels. In order to meet customer requirements regarding total costs of ownership, the lifetime is of major importance for the development of aluminum compressor wheels for turbochargers with pressure ratios beyond 6. This paper focuses on a high-pressure compressor (HPC) design with a water-cooling system for a new turbocharger generation. The development of its components and their validation based on numerically predicted and measured compressor wheel temperatures are discussed. After introducing the need for high-pressure ratios and the accompanying lifetime challenges, the paper presents the design strategy and methods of the development process. Finally, the paper summarizes the achievements obtained by this procedure. Detailed and rarely before documented temperature measurements from the rotating compressor wheel are published. As will be shown, the temperature measurements confirm the predictions from the predevelopment phase. A comparison of the temperature measurements from the recently developed compressor wheel with measurements carried out for a state-of-the-art wheel reveals the technological improvements achieved by this new generation of high-pressure compressor wheels.
Equation-Oriented Meanline Method for Axial Turbine Performance Prediction Under Choking Conditions
Authors: Anderson Lasse B. , Agromayor Roberto , Parisi Simone , Haglind Fredrik , Nord Lars O.
Published: September 2024

Meanline models play a crucial role in turbine design and system-level analyses, facilitating rapid evaluation of design concepts and prediction of off-design performance. Most of the existing meanline methods are inadequate in predicting turbine performance under choking conditions. These models either neglect the impact of losses on choking or increase the computational complexity significantly. This limitation is addressed in this work, presenting a novel meanline model. The choking state at each cascade is determined by maximizing the mass flow rate, while taking into account the effect of losses. Leveraging the method of Lagrange multipliers, the optimization problems are transformed into a set of equations that seamlessly integrate with the rest of the meanline model. The resulting system of equations is then solved simultaneously using efficient root-finding algorithms, resulting in fast and reliable convergence. Validation against experimental data from three different turbines demonstrates the model’s ability to accurately predict mass flow rate, torque, and exit flow angles across single-stage and multistage turbines, with errors typically within ±2.5% and ±5.0% for mass flow rate and torque, respectively, and within ±5 deg for flow angles. The proposed approach represents a significant advancement in meanline modeling, offering improved accuracy and computational efficiency.
Global Industry Perspectives on Postgraduate Strength and Conditioning Degrees: An Exploratory Factor Analysis
Authors: James Lachlan P. , Davids Charlie J. , Talpey Scott W. , Huynh Minh , Lidums Maris , Driller Matthew W. , Kelly Vincent G. , Gastin Paul B.
Published: September 2024

Purpose: This investigation sought to determine industry perceptions of postgraduate strength and conditioning (S&C) degrees to understand whether graduates are equipped for the demands of sport performance service roles. Methods: Survey data were collected from 111 participants employed as performance staff or in a role that recruits and supervises performance staff. The survey consisted of 3 main sections: (1) perceptions of career-development opportunities in S&C, (2) perception of S&C postgraduate programs, and (3) perceptions of employability in S&C. Exploratory factor analysis was conducted to identify the key factors considered to be of greatest relevance to career progression in S&C. Results: A 2-factor solution was achieved for each of the 3 sections, resulting in 6 total factors. These factors are Academic and Professional Development, Mentorship and Sport Diversity, Student Preparation, Require Greater Emphasis, Testing and Training, and Personal and Professional Growth. Conclusions: Postgraduate S&C programs require a broad range of placement/internship opportunities to (1) provide diverse experiences, (2) allow students to build contacts and develop professional networks, (3) gain exposure to working in high-performance environments and multidisciplinary teams, and (4) access high-quality mentors. Alongside the ability to deliver training and testing, graduates should be equipped with strong organizational and relationship-building skills. Improved graduate capabilities can raise the standards of the profession and result in enhanced service provision to athletes.
Microbial single-cell applications under anoxic conditions
Authors: Keating Ciara , Fiege Kerstin , Diender Martijn , Sousa Diana Z. , Villanueva Laura
Published: September 2024

The field of microbiology traditionally focuses on studying microorganisms at the population level. Nevertheless, the application of single-cell level methods, including microfluidics and imaging techniques, has revealed heterogeneity within populations, making these methods essential to understand cellular activities and interactions at a higher resolution. Moreover, single-cell sorting has opened new avenues for isolating cells of interest from microbial populations or complex microbial communities. These isolated cells can be further interrogated in downstream single-cell “omics” analyses, providing physiological and functional information. However, applying these methods to study anaerobic microorganisms under
in situ
conditions remains challenging due to their sensitivity to oxygen. Here, we review the existing methodologies for the analysis of viable anaerobic microorganisms at the single-cell level, including live-imaging, cell sorting, and microfluidics (lab-on-chip) applications, and we address the challenges involved in their anoxic operation. Additionally, we discuss the development of non-destructive imaging techniques tailored for anaerobes, such as oxygen-independent fluorescent probes and alternative approaches.
Evaluation of gradient strip diffusion for susceptibility testing of aztreonam–avibactam in metallo-β-lactamase-producing Enterobacterales
Authors: Lemon Jamie K. , Jankowsi-Romano Cheryl , Duong Scott , Juretschko Stefan , Streva Vincent A.
Published: September 2024

The emergence of metallo-β-lactamase (MBL)-producing Enterobacterales presents unique clinical treatment challenges. Recently developed β-lactam/ β-lactamase inhibitor combination agents, while effective against other carbapenemase-producing organisms, are notably ineffective against MBL producers. While MBLs do not hydrolyze monobactams (aztreonam), many MBL-producing organisms are resistant to aztreonam through alternate mechanisms, leaving cefiderocol as the sole monotherapy treatment option recommended for MBL producers. Recent guidelines for the treatment of MBL-harboring organisms have added combination therapy with aztreonam and ceftazidime–avibactam, using ceftazidime–avibactam as a source of the β-lactamase inhibitor avibactam. Current laboratory testing options for the combination of aztreonam–avibactam are limited to broth microdilution (BMD) and broth disk elution (BDE) methods, which are not practical in most clinical laboratories. In this study, we evaluated the performance of aztreonam/avibactam gradient strips on 103 MBL-producing Enterobacterales patient isolates as well as an additional 31 isolates from the CDC AR Bank. All MBL Enterobacterales patient isolates included in this study harbored a New Delhi metallo-β-lactamase (
bla
NDM
) gene. Essential agreement of gradient strip minimal inhibitory concentrations (MICs) for patient isolates compared to BMD was 93.2%. While there are no established breakpoints for aztreonam–avibactam, category agreement (CA) for patient isolates was 97.1% when using the CLSI aztreonam breakpoints. There were no major or very major errors observed. There were three minor errors. Precision for aztreonam–avibactam gradient strip diffusion was 100%. These data demonstrate that the use of gradient strip diffusion for aztreonam–avibactam MIC determination in MBL-producing Enterobacterales is a viable option for clinical laboratories.
Profiling inflammatory outcomes of
Candida albicans
colonization and food allergy induction in the murine glandular stomach
Authors: Zeise Karen D. , Falkowski Nicole R. , Stark Kelsey G. , Brown Christopher A. , Huffnagle Gary B.
Published: September 2024

We investigated the effects of
Candida albicans
colonization on inflammatory responses in the murine glandular stomach, which is similar to the glandular mucosa of the human stomach. We also explored whether the presence of a food allergy could exacerbate
C. albicans
-induced inflammation or if
C. albicans
would amplify allergic inflammation in the glandular stomach.
C. albicans
successfully colonized the stomach of amoxicillin-pre-treated BALB/c mice and induced gastritis in the limiting ridge with minimal inflammation in the glandular stomach. There was significant upregulation of
Il18
, calprotectin (
S100a8
and
S100a9
), and several antimicrobial peptides, but minimal induction of type 1, 2, or 3 responses in the glandular stomach. A robust type 2 response, inflammatory cell recruitment, and tissue remodeling occurred in the glandular stomach following oral ovalbumin challenges in sensitized mice. The type 2 response was not augmented by
C. albicans
colonization, but there was significant upregulation of
Il1b
,
Il12a
,
Tnf
, and
Il17a
in
C. albicans
-colonized food allergic mice. The presence of
C. albicans
did not affect the expression of genes involved in barrier integrity and signaling, many of which were upregulated during food allergy. Overall, our data indicate that
C. albicans
colonization induces minimal inflammation in the glandular stomach but augments antimicrobial peptide expression. Induction of a food allergy results in robust type 2 inflammation in the glandular stomach, and while
C. albicans
colonization does not exacerbate type 2 inflammation, it does activate a number of innate and type 3 immune responses amid the backdrop of allergic inflammation.

IMPORTANCE

Food allergy continues to be a growing public health concern, affecting at least 1 in 10 individuals in the United States alone. However, little is known about the involvement of the gastric mucosa in food allergy. Gastrointestinal
Candida albicans
colonization has been reported to promote gastrointestinal inflammation in a number of chronic diseases. Using a mouse model of food allergy to egg white protein, we demonstrate regionalization of the inflammatory response to
C. albicans
colonization, induction of robust type 2 (allergic) inflammation in the stomach, and augmentation of innate and type 3 responses by
C. albicans
colonization during food allergy.
Chlamydia
-driven ISG15 expression dampens the immune response of epithelial cells independently of ISGylation
Authors: Wu Yongzheng , Liu Chang , Tang Chongfa , Niragire Béatrice , Levy-Zauberman Yaël , Adapen Cindy , Vernay Thomas , Hugueny Juliette , Baud Véronique , Subtil Agathe
Published: September 2024

Excessive inflammation upon
Chlamydia trachomatis
infection can cause severe damages in the female genital tract. This obligate intracellular bacterium develops mainly in epithelial cells, whose innate response contributes to the overall inflammatory response to infection. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) stimulates interferon γ (IFNγ) production and is required for bacterial clearance in several infectious contexts. Here, we describe and investigate the consequences of the increase in ISG15 expression by epithelial cells infected with
C. trachomatis
. Infection of HeLa cells and primary ecto-cervical epithelial cells resulted in a transcriptional upregulation of
ISG15
expression. This did not involve the canonical type I interferon (IFN-I) signaling pathway and depended instead on the activation of the STING/TBK1/IRF3 pathway. The absence or reduction of ISG15 synthesis led to increased production of several cytokines and chemokines, including interleukin (IL) 6 and IL8. This implicates that ISG15 normally dampens the immune response induced by
C. trachomatis
infection in epithelial cells. ISG15 exerted its control from an intracellular location, but without involving ISGylation. Finally, higher levels of inflammation and delayed bacterial clearance were observed in the genital tracts of ISG15-KO mice infected by
C. trachomatis
compared with wild-type animals; however, IFNγ production was unchanged. Altogether, our data show that ISG15 expression acts as a brake on the immune response to
C. trachomatis
infection in epithelial cells and limits bacterial burden and inflammation in mice.

IMPORTANCE

Infection of epithelial cells by
Chlamydia trachomatis
elicits an innate immune response by these cells. The signaling pathways involved, and their outcomes, are still very poorly understood. In this paper, we described how
Chlamydia
infection triggered the expression of ISG15, a small molecule normally associated to type I interferon (IFN-I) signaling and control of INF-γ production. ISG15 synthesis by epithelial cells attenuated their immune response to
Chlamydia
infection. In mice, we observed that ISG15 displayed a marginal role in modulating the production of IFN-γ, a key component of the host immune response to infection, but facilitated bacterial clearance. Overall, our study strengthens the importance of ISG15 not only in the resolution of viral but also of bacterial infection and document its role of “immune brake” in the context of
Chlamydia
infection.
Hepatic sinusoidal obstruction syndrome after immune-checkpoint-inhibitor therapy: when the liver sends SOS
Authors: Kasper Philipp , Fischer Anne Kristin , Schumacher Jan Christoph
Published: September 2024

A woman in her 50s presented to the hospital with new-onset jaundice and ascites. Her medical history included a melanoma of the right shoulder, diagnosed 8 months before, for which she had received four cycles of ipilimumab and nivolumab. Due to the oncological history and previous immunotherapy, an immune-checkpoint-inhibitor (ICI)-induced hepatitis was suspected, and a high-dose corticosteroid treatment was initiated. However, as there was no improvement in the liver function tests, a percutaneous liver biopsy was performed for further diagnostic clarification. Histological analysis ultimately identified a hepatic sinusoidal obstruction syndrome (SOS) as the underlying cause of liver dysfunction and portal hypertension. ICI-related hepatic SOS represents an extremely rare adverse event related to immunotherapy that should be considered in all patients with treatment-refractory ICI-related hepatotoxicity and clinical signs of portal hypertension.
Bridging the Gap: A Comprehensive Study on Traditional Chinese Medicine Strategies for Managing Adult Irritable Bowel Syndrome
Authors: Wei Dong-Jue , Li Hui-Juan , Lyu Ai-Ping , Bian Zhao-Xiang , Siah Kewin T. H. , Zhong Linda L. D.
Published: September 2024

Recent studies have witnessed the incorporation of herbal medicine into the management of Disorders of Gut-Brain Interactions (DGBIs), reflecting a paradigm shift toward holistic healing modalities. However, there still exists a substantial gap in comprehending the utilization of Traditional Chinese Medicine (TCM) for Irritable Bowel Syndrome (IBS), particularly beyond the confines of China. This study endeavors to bridge this knowledge gap by meticulously identifying existing guidelines, critically reviewing TCM practices, and crafting contemporary treatment recommendations. We systematically searched several databases to retrieve related evidence in June 2023. Firstly, we employed the AGREE II tool to evaluate the recommended for use of TCM in the treatment of IBS, establishing a structured treatment selection hierarchy for different TCM patterns of IBS patients. Subsequently, we conducted an expert questionnaire to gain insights into the common treatment methods and medication choices practiced by clinical TCM doctors. Based on CM theory and experts’ opinions, IBS with predominant Diarrheal (IBS-D) is divided into five Chinese medicine syndrome patterns, and IBS with predominant Constipation (IBS-C) is classified to four. A total of 22[Formula: see text]CM prescriptions were recommended for the management of IBS, 13 for IBS-D and 9 for IBS-C. The findings provide IBS patients with enhanced treatment choices while offering clinical physicians more specific treatment regimens. This research is the first to conduct a comprehensive study that combines guidelines with real clinical practices in the realm of TCM IBS treatment. This serves as a foundation for providing more personalized treatment options and improving the quality of life for patients.
Research Progress of Chinese Medicine in the Regulation of Liver Fibrosis-Related Signaling Pathways
Authors: Zheng Shihao , Xue Chengyuan , Li Size , Qi Wenying , Zao Xiaobin , Li Xiaoke , Wang Wei , Liu Qiyao , Cao Xu , Zhang Peng , Ye Yongan
Published: September 2024

Liver fibrosis is a common complication of chronic liver disease, significantly affecting patients’ quality of life and potentially leading to cirrhosis and hepatocellular carcinoma. Despite advancements in modern medicine, the treatment of liver fibrosis remains limited and challenging. Thus, identifying new therapeutic strategies is of great clinical importance. Signaling pathways related to liver fibrosis play a crucial regulatory role in immune response and inflammation. Aberrant activation of specific pathways, such as the NF-κB signaling pathway, results in the overexpression of genes associated with liver inflammation and fibrosis, thereby promoting the progression of liver fibrosis. Chinese medicine offers unique potential advantages as a therapeutic approach. Recent studies have increasingly demonstrated that certain Chinese medicines can effectively treat liver fibrosis by regulating relevant signaling pathways. The active ingredients in these medicines can inhibit hepatic inflammatory responses and fibrotic processes by interfering with these pathways, thus reducing the severity of liver fibrosis. This paper aims to investigate the mechanisms of Chinese medicine in treating liver fibrosis and its modulation of related signaling pathways. Additionally, it discusses the prospects of the clinical application of these treatments and provides valuable references for further research and clinical practice.
Isoliquiritigenin Suppresses Breast Tumor Development by Enhancing Host Antitumor Immunity
Authors: Yuan Chun-Lu , Yang Xiao-Lu , Sun Lei , Jiang Yi-Xin , Zhang Dan-Dan , Huang Shuang
Published: September 2024

Isoliquiritigen (ISL), a constituent of licorice, has been shown to possess antitumorigenic effects in diverse cancer types. In this study, we observed that ISL suppressed breast tumor development significantly more effectively in immunocompetent mice than in immunocompromised ones. In exploring the cause of such a discrepancy, we detected robust tumor infiltration of CD8[Formula: see text] T lymphocytes in mice treated with ISL, not seen in tumors derived from vehicle-treated mice. Moreover, we found a dramatic reduction in PD-L1 in both experimental breast tumors and cultured breast cancer cells upon ISL treatment. In further experiments, we showed that ISL selectively elevated miR-200c in breast cancer and confirmed that PD-L1 mRNA is the target of miR-200c in both murine and human breast cancer cells. ISL suppression of PD-L1 was functionally linked to miR-200c/ZEB1/2 because (1) ISL diminished ZEB1/2; (2) knockdown of ZEB1/2 led to the disappearance of PD-L1; and (3) miR-200c antagomiR disabled ISL to reduce PD-L1. We found evidence that ISL reduced the level of PD-L1 by simultaneously intercepting the ERK and Src signaling pathways. In agreement with clinical finding that PD-L1 antibodies enhance efficacy of taxane-based therapy, we showed that ISL improved the tumoricidal effects of paclitaxel in an orthopedic murine breast tumor model. This study demonstrates that ISL-led tumor suppression acts through the augmentation of host antitumor immunity.
Honokiol Exhibits Anti-Tumor Effects in Breast Cancer by Modulating the miR-148a-5p-CYP1B1 Axis
Authors: Han Xuejiao , Cheng Yuan , Jiang Zedong , Alu Aqu , Ma Xuelei
Published: September 2024

Breast cancer (BC) is the most frequently diagnosed malignancy in female patients. There is a significant lack of therapeutic strategies for BC, particularly triple-negative breast cancer (TNBC). Honokiol (HNK), a lignin extracted from the Magnolia genus plant, has demonstrated numerous pharmacological effects. Therefore, this study aims to investigate the antitumor effect of HNK on BC cells and employ high-throughput sequencing to elucidate its potential mechanism. We found that HNK significantly inhibited proliferation and induced apoptosis on BC cell lines in a dose-dependent manner. Moreover, HNK treatment suppressed migration and colony formation and initiated the intrinsic apoptotic pathway specifically in MDA-MB-231 cells. High-throughput sequencing and bioinformatics analysis revealed that miR-148a-5p expression was significantly up-regulated, whereas CYP1B1 expression was down-regulated following HNK treatment. Importantly, survival analysis based on TCGA database showed high miR-148a-5p expression was correlated with a better prognosis for BC patients. Inhibition of miR-148a-5p by inhibitor not only increased cell viability but also attenuated apoptosis induced by HNK. Finally, a strong synergistic effect between HNK and paclitaxel was observed in vitro. In conclusion, our study validated the antitumor efficacy of HNK against human BC cells and elucidated its underlying mechanism through high-throughput sequencing, thereby providing compelling evidence for further exploration of the potential clinical application of HNK towards the treatment of BC.
A diverse array of optical solitons of generalized nonlinear dispersive mK(m,n) model
Authors: Seadway Aly R. , Ali Asghar , Bekir Ahmet , Cevikel Adem C. , Alp Murat
Published: September 2024

The generalized [Formula: see text] model is used to portray the movement of nonlinear waves by applying four mathematical methods with assistance of Mathematica software. These methods are called enhanced simple equation (SE) method, Exp[Formula: see text]-expansion method, [Formula: see text]-expansion method and modified F-expansion method. For physical behavior, few solutions are plotted graphically in the form of two-dimensional (2D) and three-dimensional (3D). The techniques and soliton solutions that are developed provide computational tools for additional research in this area. With this work, we have gained a better knowledge of soliton motion and how it is used in dynamical systems and other related technologies. Hence, this work will help physicists envision some new ideas and hypotheses in nonlinear science.
China’s Shift from CMI to MCF: Military Modernization and the Defense Industry at the Core
Authors: BINDU GOKIREDDY HIMA , JASH AMRITA
Published: September 2024

The concept of civil-military integration (CMI) was officially introduced in the 1990s in the United States to transform industrial bases in defense amidst shifting geopolitical dynamics. CMI aims to blur the lines between civilian and military sectors, fostering the sharing of resources and technological advancement. This paper looks at the practice of CMI in China and its shift to military–civil fusion (MCF). Though the concept only emerged in the late 20th century, CMI in its other forms such as defense conversion and diversification has been practiced in China since the Mao era. However, the transition from CMI to MCF underscores the evolution of China’s strategic priorities, aligning military and civilian resources for technological advancement and national rejuvenation. Under Xi Jinping’s leadership, China has elevated MCF into a national strategy. MCF is considered essential for achieving China’s strategic goals and has entered a rapid stage of development, reflecting Xi’s commitment to modernizing the PLA and advancing national rejuvenation to realize the “Chinese Dream.” China’s efforts to achieve self-sufficiency in defense production and assert its military prowess on the global stage propelled by the MCF strategy under Xi Jinping have global geopolitical implications.
RESOURCE COMMITMENT AND PARTNER SELECTION IN ASYMMETRIC CORPORATE-STARTUP COLLABORATIONS
Authors: PAUER SOPHIA , MATZLER KURT , HERRMANN STELLA
Published: September 2024

Startups and established firms collaborate in order to leverage complementary resources and innovative capabilities to sustain a competitive advantage. By forming alliances, startups are able to mitigate challenges connected to their smallness and lack of legitimacy. However, the underlying criteria by which startups screen and select potential collaboration partners in such asymmetric collaborations remain poorly understood. This paper examines the dynamics of these asymmetric collaborations, exploring the motives, selection criteria, and the willingness of startups to partner from a resource-based perspective. We conduct a conjoint experiment to examine the relationship between diverse resource commitment types and startups’ willingness to partner. The findings of the study confirm a strong influence of financial, technological, managerial, and physical resources in a startup’s decision-making process regarding partner selection. Notably, the attractiveness of a partner was found to diminish when they possess a similar market portfolio, potentially fostering future competition. Consequently, startups must implement effective control and protection mechanisms to prevent opportunistic behaviours from collaboration partners operating in the same market. To contribute to the existing literature, we adopt a resource-based theoretical lens that emphasises the pivotal role of capabilities in a startup’s decision-making process and demonstrates their influential role in forging successful collaborations with established partners. Ultimately, our findings enhance the understanding of the partner selection criteria, offering valuable insights for new ventures seeking beneficial partnerships at the early stages of a collaboration.
Translated sums on special family of quasi-primitive sequences
Authors: Laib Ilias
Published: September 2024

A sequence [Formula: see text] of strictly positive integers is said to be quasi-primitive if there are no three distinct terms [Formula: see text] and [Formula: see text] such that [Formula: see text]. Erdős conjectured that the sum [Formula: see text] where [Formula: see text] is the sequence of all powers of prime numbers and [Formula: see text][Formula: see text]. Recently, Laib et al. proved that the analogous conjecture of Erdős [Formula: see text] is false for [Formula: see text] over the quasi-primitive sequence of semiprimes. In this paper, by constructing a family of quasi-primitive sequences from sequences of [Formula: see text]-almost primes and the powers of the prime numbers, we extend this falsity up to [Formula: see text].
Northcott property and universality of higher degree forms
Authors: Prakash Om
Published: September 2024

Let [Formula: see text] be a totally real number field, [Formula: see text] a positive integer, and [Formula: see text] a higher degree form over [Formula: see text]. We prove that there are at most finitely many totally real extensions [Formula: see text] of degree [Formula: see text] such that [Formula: see text] over [Formula: see text] is universal. Further, we show that there are no universal forms over totally real infinite extensions of [Formula: see text] having the Northcott property.
IUAC: Inaudible Universal Adversarial Attacks Against Smart Speakers
Authors: Sun Haifeng , Du Haohua , Yu Xiaojing , Hou Jiahui , Zhang Lan , Li Xiangyang
Published: September 2024

Intelligent voice systems are widely utilized to control smart home applications, which raises significant privacy and security concerns. Recent studies have revealed their vulnerability to adversarial attacks, replay attacks, and so on. However, these attacks rely on the victim’s voice data. In our work, we investigate a stealthy and command-independent attack that does not necessitate collecting victims’ voices. Our proposed attack, IUAC, misleads the voice system to go against the victim’s will, regardless of the commands delivered. Our core concept is to train highly robust attack commands through the construction of diverse data, rendering the user’s commands negligible. To achieve stealthy attacks, we leverage a high-frequency carrier to construct an inaudible universal adversarial command. Extensive experiments conducted with real-world datasets demonstrate that our attack system attains an average attack success rate of 96% while resisting environmental interference. Moreover, our attack success rate against real-world voice systems is 4.52× higher than the state-of-the-art. Finally, we propose an effective defense mechanism and provide experimental tests to validate its efficacy.
Retail CBDC: Implications for Banking and Financial Stability
Authors: Infante Sebastian , Kim Kyungmin , Orlik Anna , Silva André F. , Tetlow Robert
Published: September 2024

This article reviews the literature examining how the introduction of a retail central bank digital currency (CBDC) would affect a modern economy, focusing on the implications for the banking sector and for financial stability. A CBDC can improve welfare by reducing financial frictions, countering market power in deposit markets, encouraging financial inclusion, and enhancing the payment system. However, a CBDC also entails noteworthy risks, including the possibility of bank disintermediation and associated contraction in bank credit, as well as potential adverse effects on financial stability. The recycling of the new CBDC liability through asset purchases or lending by the central bank plays an important role in determining the economic consequences of the introduction of a CBDC, raising fundamental questions about the footprint of central banks in the financial system. Ultimately, the effects of a CBDC depend critically on its design features, particularly remuneration.
Hypoxia-induced TIMAP upregulation in endothelial cells and TIMAP-dependent tumor angiogenesis
Authors: Aburahess Salah , Li Laiji , Hussain Aashiq , Obeidat Marya , Alavi Parnian , Azad Abul K. , Jahroudi Nadia , Ballermann Barbara J.
Published: September 2024

The protein phosphatase 1 regulatory subunit TGFβ-inhibited membrane associated protein (TIMAP), known to activate AKT in endothelial cells (EC), was shown here to be repressed by bone morphogenetic factor 9 (BMP9). Hypoxia and angiogenic growth factors induced TIMAP expression by inhibiting the BMP9 pathway. In a mouse breast cancer model, TIMAP deletion inhibited tumor angiogenesis and tumor growth. Therefore, the proangiogenic functions of TIMAP are induced by hypoxia and angiogenic growth factors.
Animal models of haploinsufficiency revealed the isoform-specific role of GSK-3 in HFD-induced obesity and glucose intolerance
Authors: Gupte Manisha , Umbarkar Prachi , Lemon Jacob , Tousif Sultan , Lal Hind
Published: September 2024

The precise isoform-specific role of GSK-3 in obesity-induced glucose intolerance is unclear. To overcome the limitations of pharmacological GSK-3 inhibitors (not isoform-specific) and tissue-specific genetic models, in the present study, we created novel inducible heterozygous mouse models of GSK-3 inhibition that allowed us to delete the gene globally in an isoform-specific and temporal manner to determine the isoform-specific role of GSK-3 in obesity-induced glucose intolerance.
Deubiquitinases in skeletal muscle—the underappreciated side of the ubiquitination coin
Authors: Du Wayne X. , Goodman Craig A. , Gregorevic Paul
Published: September 2024

Ubiquitination is a posttranslational modification that plays important roles in regulating protein stability, function, localization, and protein-protein interactions. Proteins are ubiquitinated via a process involving specific E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. Simultaneously, protein ubiquitination is opposed by deubiquitinating enzymes (DUBs). DUB-mediated deubiquitination can change protein function or fate and recycle ubiquitin to maintain the free ubiquitin pool. Approximately 100 DUBs have been identified in the mammalian genome, and characterized into seven classes [ubiquitin-specific protease (USP), ovarian tumor proteases (OTU), ubiquitin C-terminal hydrolase (UCH), Machado-Josephin disease (MJD), JAB1/MPN/Mov34 metalloprotease (JAMM), Ub-containing novel DUB family (MINDY), and zinc finger containing ubiquitin peptidase (ZUP) classes]. Of these 100 DUBs, there has only been relatively limited investigation of 20 specifically in skeletal muscle cells, in vitro or in vivo, using overexpression, knockdown, and knockout models. To date, evidence indicates roles for individual DUBs in regulating aspects of myogenesis, protein turnover, muscle mass, and muscle metabolism. However, the exact mechanism by which these DUBs act (i.e., the specific targets of these DUBs and the type of ubiquitin chains they target) is still largely unknown, underscoring how little we know about DUBs in skeletal muscle. This review endeavors to comprehensively summarize the current state of knowledge of the function of DUBs in skeletal muscle and highlight the opportunities for gaining a greater understanding through further research into this important area of skeletal muscle and ubiquitin biology.
A long-term high-fat diet induces differential gene expression changes in spatially distinct adipose tissue of male mice
Authors: Alradi Malak , Askari Hassan , Shaw Mark , Bhavsar Jaysheel D. , Kingham Brewster F. , Polson Shawn W. , Fancher Ibra S.
Published: September 2024

A long-term high-fat diet induced the expression of more than 980 unique genes across subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The high-fat diet also induced the differential expression of nearly 1,000 AT genes. We identified four genes that were oppositely expressed in SAT versus VAT in response to the high-fat diet and propose that these genes in particular may serve as promising targets aimed at resolving VAT dysfunction in obesity.