bluuebunny/crossref_metadata_2025 huggingface dataset:
Monolithic Electrically‐Driven Retroreflector Based on Gold Nanoparticles Embedded in Ferroelectric Polymer
Authors: Ligorio Giovanni , Truong Vinh‐Binh , Schitter Georg , List‐Kratochvil Emil
Published: February 2024

The surface plasmon resonance (SPR) observed in metal nanostructures finds application in biosensing, optical communication technologies, and neuromorphic computing. There it enables the detection and transduction of dielectric environment changes in the vicinity of the metal nanostructure. Combining this principle with materials where the dielectric environment can be electrically modulated, it becomes possible to realize active optoelectronic plasmonic devices specifically designed for optical communication technologies. In this work, the use of an organic ferroelectric polymer to reversibly modulate the localized SPR (LSPR) of gold nanoparticles (AuNPs) inducing a reversible spectral shift of the resonance is investigated. The proposed plasmonic modulator is based on a two‐terminal device composed of AuNPs deposited on a transparent conductive electrode, covered by a ferroelectric polymer poly(vinylidene fluoride‐co‐trifluoroethylene) with a metallic electrode on top also serving as the mirror. By applying a voltage bias between the two electrodes, an electric field is generated within the device, enabling precise control over the dielectric environment of the AuNPs and thereby modulating the LSPR. It is demonstrated that this concept can be easily fabricated, potentially flexible, lightweight, and robust, making it an attractive choice for optical communication devices, particularly as a free space modulating retroreflector.
Natural xanthones as modulators of the Nrf2/ARE signaling pathway and potential gastroprotective agents
Authors: Gunter Natalie Vivien , Teh Soek Sin , Jantan Ibrahim , Law Kung Pui , Morita Hiroyuki , Mah Siau Hui
Published: February 2024

Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti‐inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action–particularly mangiferin (2), α‐mangostin (3), and γ‐mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.
Making a case for nature‐based solutions for a sustainable built environment in Africa
Authors: Aghimien Douglas , Aliu John , Chan Daniel W. M. , Aigbavboa Clinton , Awuzie Bankole
Published: February 2024

The potential of using nature‐based solutions to address issues of climate change has continued to gain momentum, especially in developed nations. However, the same cannot be said for developing countries, particularly in Africa, where the knowledge and awareness of natural solutions are low, and research on their application within the built environment is scant. Using a sciento‐metric and narrative review of published literature, this paper makes a case for research exploration on nature‐based solutions for a sustainable built environment in Africa. The findings revealed an opportunity for significant research contributions on nature‐based solutions in addressing flood risk management, climate change and urban planning, water quality and carbon emission, sustainable development, and green infrastructure and urban development. These areas are the critical focus of past studies explored. Also, the findings offer guidance for further studies to be conducted in less explored areas, such as carbon sequestration, greenhouse gases, energy utilisation, indoor comfort, and numeric models for using nature‐based solutions within the African context. The findings of the study offer an excellent theoretical background to direct researchers and practitioners who seek to attain and promote sustainable built environments through nature‐based solutions, especially in Africa.
The cue‐ball effect: How an advantaged firm's closer competitors can propagate the impact of its advantage to more distant competitors
Authors: Balasubramanian Natarajan , Makadok Richard , Chiu Wan‐Ting
Published: February 2024

Research Summary

Cost advantage helps a firm at the expense of its rivals, but may hurt some rivals worse than others. Conventional wisdom suggests that an advantaged firm will do more harm to closer competitors, but the opposite may occur if competitors can reposition themselves. Closer competitors have stronger incentives to reposition away from the advantaged firm, thereby potentially encroaching on rivals more distant from the advantaged firm and propagating the harm to them like the cue ball in billiards transfers energy from cue stick to target ball. Our formal model compares an advantaged firm's closer and farther competitors, when repositioning is allowed or prohibited, and demonstrates when its advantage hurts farther competitors worse than closer ones. We provide an illustrative case study from grocery retailing.

Managerial Summary

When Walmart brought its advantage in distribution efficiency to the low end of the grocery retailing industry, it displaced the inefficient downscale incumbent Winn‐Dixie in many geographic areas. One might have expected such increased efficiency at the low end of the market to hurt midscale supermarkets like Kroger more than premium grocers like Whole Foods, yet the opposite occurred. Why? In a word, repositioning. Midscale competitors retreated away from Walmart by repositioning upscale via renovations, which thereby transferred the impact to premium rivals who could not escape any further upscale. Our economic model of this “cue‐ball effect” predicts that the impact propagated onto upper‐end competitors is greater in markets with less income inequality, and our empirical results are consistent with this prediction.
The effect of flatter hierarchy on applicant pool gender diversity: Evidence from experiments
Authors: Hurst Reuben , Lee Saerom (Ronnie) , Frake Justin
Published: February 2024

Research Summary

This article investigates how job seekers' perceptions of an employer's formal hierarchy affect the size and gender composition of its applicant pool. Building on the literature on gendered organizations and organizational design, we develop opposing perspectives on these relationships. To arbitrate between these perspectives, we first conduct a field experiment in partnership with a hiring firm. We find that featuring a flatter hierarchy in recruiting materials does not significantly affect the size of the applicant pool, but significantly decreases women's representation within it. Our follow‐up survey experiment identifies several potential mechanisms (e.g., perceptions of career progression, informality, workload, and fit). Our findings imply that firms' growing tendency to adopt flatter hierarchies could inadvertently undermine efforts to attract a greater proportion of women applicants.

Managerial Summary

Using a pair of labor market experiments, this study finds that characterizing a hiring firm's hierarchy as “flatter” with fewer management levels reduces women's representation in the applicant pool. We show that this decrease in the share of women applicants is likely driven by the fact that women, compared to men, perceive flatter hierarchies as more likely to present difficulties in fitting in, burden them with more work, and provide fewer opportunities for career progression. These findings suggest that, to mitigate workplace gender segregation, organizations with flatter structures may benefit from de‐emphasizing their organizational hierarchies in recruitment efforts. Moreover, companies should consider how their organizational attributes contribute to fostering a more inclusive work environment.
Efficient Photothermal Sensor Based on Coral‐Like Hollow Gold Nanospheres for the Sensitive Detection of Sulfonamides
Authors: Xiao Xiaoyue , Yu Sha , Zhang Gan , Chen Zongyou , Hu Hong , Lai Xiaocui , Liu Daofeng , Lai Weihua
Published: February 2024

Gold nanoparticles (AuNPs), universally regarded as colorimetric signal reporters, are widely employed in lateral flow immunoassays (LFIAs). However, it is difficult for AuNPs‐LFIA to achieve a wide range and sensitive detection. Herein, novel coral‐like hollow gold nanospheres (CHGNPs) are synthesized. The growth of gold nanospheres can be regulated to obtain a multibranched and hollow construction. The obtained CHGNPs possess intense broadband absorption across the visible to near‐infrared region, exhibiting a high molar extinction coefficient of 14.65 × 1011 M−1 cm−1 and a photothermal conversion efficiency of 79.75%. Thus, the photothermal/colorimetric dual‐readout LFIA is developed based on CHGNPs (CHGNPs‐PT‐LFIA and CHGNPs‐CM‐LFIA) to effectively improve the detection sensitivity and broaden the detection range in regard to sulfonamides (SAs). The limits of detection of the CHGNPs‐PT‐LFIA and CHGNPs‐CM‐LFIA reached 1.9 and 2.8 pg mL−1 for the quantitative detection of sulfaquinoxaline, respectively, which are 6.3‐fold and 4.3‐fold lower than that of the AuNPs‐LFIA. Meanwhile, the CHGNPs‐PT‐LFIA broadened the detection range to three orders of magnitude, which ranged from 2.5 to 5000 pg mL−1. The synthesized photothermal CHGNPs have been proven effective in improving the performance of the LFIA and provide a potential option for the construction of sensing platforms.
Enzyme‐Directed and Organelle‐Specific Sphere‐to‐Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells
Authors: Gan Shenglong , Yang Liu , Heng Yiyuan , Chen Qingxin , Wang Dongqing , Zhang Jie , Wei Wenyu , Liu Zhiyang , Njoku Demian Ifeanyi , Chen Jian Lin , Hu Yi , Sun Hongyan
Published: February 2024

Employing responsive nanoplatforms as carriers for photosensitizers represents an effective strategy to overcome the challenges associated with photodynamic therapy (PDT), including poor solubility, low bioavailability, and high systemic toxicity. Drawing inspiration from the morphology transitions in biological systems, a general approach to enhance PDT that utilizes enzyme‐responsive nanoplatforms is developed. The transformation of phosphopeptide/photosensitizer co‐assembled nanoparticles is first demonstrated into nanofibers when exposed to cytoplasmic enzyme alkaline phosphatase. This transition is primarily driven by alkaline phosphatase‐induced changes of the nanoparticles in the hydrophilic and hydrophobic balance, and intermolecular electrostatic interactions within the nanoparticles. The resulting nanofibers exhibit improved ability of generating reactive oxygen species (ROS), intracellular accumulation, and retention in cancer cells. Furthermore, the enzyme‐responsive nanoplatform is expanded to selectively target mitochondria by mitochondria‐specific enzyme sirtuin 5 (SIRT5). Under the catalysis of SIRT5, the succinylated peptide/photosensitizer co‐assembled nanoparticles can be transformed into nanofibers specifically within the mitochondria. The resulting nanofibers exhibit excellent capability of modulating mitochondrial activity, enhanced ROS formation, and significant anticancer efficacy via PDT. Consequently, the enzyme‐instructed in situ fibrillar transformation of peptide/photosensitizers co‐assembled nanoparticles provides an efficient pathway to address the challenges associated with photosensitizers. It is envisaged that this approach will further expand the toolbox for enzyme‐responsive biomaterials for cancer therapy.
Hierarchical Porous Nonprecious High‐entropy Alloys for Ultralow Overpotential in Hydrogen Evolution Reaction
Authors: Wang Chunyang , Zhao Shen , Han Guoqiang , Bian Haowei , Zhao Xinrui , Wang Lina , Xie Guangwen
Published: February 2024

Water electrolysis is considered the cleanest method for hydrogen production. However, the widespread popularization of water splitting is limited by the high cost and scarce resources of efficient platinum group metals. Hence, it is imperative to develop an economical and high‐performance electrocatalyst to improve the efficiency of hydrogen evolution reaction (HER). In this study, a hierarchical porous sandwich structure is fabricated through dealloying FeCoNiCuAl2Mn high‐entropy alloy (HEA). This free‐standing electrocatalyst shows outstanding HER performance with a very small overpotential of 9.7 mV at 10 mA cm−2 and a low Tafel slope of 56.9 mV dec−1 in 1 M KOH solution, outperforming commercial Pt/C. Furthermore, this electrocatalytic system recorded excellent reaction stability over 100 h with a constant current density of 100 mA cm−2. The enhanced electrochemical activity in high‐entropy alloys results from the cocktail effect, which is detected by density functional theory (DFT) calculation. Additionally, micron‐ and nano‐sized pores formed during etching boost mass transfer, ensuring sustained electrocatalyst performance even at high current densities. This work provides a new insight for development in the commercial electrocatalysts for water splitting.
Density‐Functional Theory Studies on Photocatalysis and Photoelectrocatalysis: Challenges and Opportunities
Authors: Lin Chun‐Han , Rohilla Jyoti , Kuo Hsuan‐Hung , Chen Chun‐Yi , Mark Chang Tso‐Fu , Sone Masato , Ingole Pravin P. , Lo Yu‐Chieh , Hsu Yung‐Jung
Published: February 2024

Density‐functional theory (DFT) is pivotal in the advancement of photocatalysis and photoelectrocatalysis. Its capability to explore electronic structures of materials contributes significantly to clarifying the mechanisms of photocatalytic (PC) and photoelectrocatalytic (PEC) processes. DFT calculations enable a deeper understanding of how these processes work at a molecular level, which is essential for designing versatile photocatalysts and photoelectrodes and optimizing reaction pathways. In this perspective, key PC and PEC applications, such as H2 production, CO2 reduction, dye degradation, and N2 reduction, where DFT is instrumental in optimizing materials designs and reaction pathways, are highlighted. Exploration on the synergy between experimental research and DFT calculations is highlighted, which is crucial for the development of efficient and environmentally friendly energy solutions. The discussion further extends to challenges and future directions, emphasizing the need for incorporating factors, including discrepancy in scale, light illumination, electrolyte presence, and applied bias, into DFT calculations, to achieve a more comprehensive understanding of PC and PEC systems. In this perspective, it is aimed to provide a holistic view of the current state and potential advancements in photocatalyst and photoelectrode modeling, thereby guiding future research toward more effective and sustainable energy and chemical production processes in PC and PEC systems.
Catalyzing Sustainable Water Splitting with Single Atom Catalysts: Recent Advances
Authors: Alam Nasar , Noor Tayyaba , Iqbal Naseem
Published: February 2024

Electrochemical water splitting for sustainable hydrogen and oxygen production have shown enormous potentials. However, this method needs low‐cost and highly active catalysts. Traditional nano catalysts, while effective, have limits since their active sites are mostly restricted to the surface and edges, leaving interior surfaces unexposed in redox reactions. Single atom catalysts (SACs), which take advantage of high atom utilization and quantum size effects, have recently become appealing electrocatalysts. Strong interaction between active sites and support in SACs have considerably improved the catalytic efficiency and long‐term stability, outperforming their nano‐counterparts. This review‘s first section examines the Hydrogen Evolution Reaction (HER) and the Oxygen Evolution Reaction (OER). In the next section, SACs are categorized as noble metal, non‐noble metal, and bimetallic synergistic SACs. In addition, this review emphasizes developing methodologies for effective SAC design, such as mass loading optimization, electrical structure modulation, and the critical role of support materials. Finally, Carbon‐based materials and metal oxides are being explored as possible supports for SACs. Importantly, for the first time, this review opens a discussion on waste‐derived supports for single atom catalysts used in electrochemical reactions, providing a cost‐effective dimension to this vibrant research field. The well‐known design techniques discussed here may help in development of electrocatalysts for effective water splitting.
ATwo‐StageMethod for Order Selection inModel‐FreePredictive Control
Authors: Jiravit Pratvittaya , Yamamoto Shigeru
Published: February 2024

One of the primary advantages of model‐free predictive control over conventional methods is that it does not use any mathematical models and relies only utilizes measured input/output data from the storage. The capability of model‐free predictive control has been already demonstrated in nonlinear systems using linear and polynomial regression for data storage. However, identifying the appropriate order that aligns with the actual system order remains a primary challenge, selecting an incorrect order may result in increasing redundant terms, ultimately leading to instability issues. In this study, we employed the Singular Value Decomposition (SVD) order selection technique, combined with the Bayesian Information Criterion (BIC), to identify the appropriate input and output orders of the system as well as the optimal horizon order in predictive control. This combined technique was subsequently applied to determine the appropriate order for model‐free predictive control. Our findings confirmed the effectiveness of the proposed method using numerical simulations in both linear and nonlinear systems. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.
Purification of dredged water by magnetic coagulation: Response surface optimization and dissolved organic matter removal characteristics
Authors: Xiao Yuanting , Feng Jingwei , Zhang Liu , Yang Yulin , Zhou Xuyang , Xu Deqian , Gong Miao , Yin Hao , Yuan Shoujun
Published: February 2024

In the present study, magnetic coagulation was used to treat dredged water and the response surface method was used to optimize process parameters. The dissolved organic matter (DOM) removal characteristics were characterized by three‐dimensional fluorescence spectrometry and ultra‐high resolution mass spectrometry. During the magnetic coagulation process, the suspended solids (SS) removal rate increased initially and then decreased under conditions of increasing magnetic powder dosage and stirring rate. After magnetic coagulation and precipitation for 20 min, the contents of SS, ammonia nitrogen, chemical oxygen demand, and total phosphorus in the treated dredged water met the requirements of the discharge standard (GB8978–1996, China). Three‐dimensional fluorescence results showed that magnetic coagulation selectively removed fulvic acids and humic acid substances. After magnetic coagulation with precipitation for 10 min and 20 min, the total relative content of lignins, tannins, proteins, lipids, aminosugars, unsaturated hydrocarbons, condensed aromatic structures, and carbohydrates decreased by 26.3% and 39.4%, respectively. After magnetic coagulation, the distribution range of small molecule DOM shifted to the low H/C and high O/C regions. This study provides a novel perspective for studies on the removal of DOM in dredged water by magnetic coagulation.

Practitioner Points

SS and DOM removal were significantly enhanced by the use of magnetic coagulation.

SS removal efficiency was affected by stirring rate and magnetic powder dosage.

Magnetic coagulation selectively removed fulvic acids and humic acid substances.

DOM molecule shifted to low H/C and high O/C regions after magnetic coagulation.
Mexico
Authors: Unda-Gutierrez Mónica , Reyes Alejandra
Published: February 2024

The decentralisation that began in Mexico in the early 1980s was one of a series of changes to have shaped the evolution of the country’s system of municipal government. Despite the still-limited nature of local governance, and recent attempts under the last two federal administrations to recentralise power, municipalities are increasingly relevant actors in Mexico’s economic, social, and political life. This chapter provides a framework for understanding the evolution and current functioning of municipal government in Mexico. It shows how decentralisation measures have changed the nature of municipal government, and at the same time examines the limits imposed on it by legal strictures, fiscal challenges, and intergovernmental relations.
Spain
Authors: Velasco Caballero Francisco
Published: February 2024

In general terms, the Spanish system of local government under the current Constitution (1978) is relatively stable. Various economic crises and social and political changes (such as the emergence of new political parties at the state, regional, and local levels) have brought about several adjustments in the local government system, but have not modified its pillars. Although both state and autonomous communities (regions) tend to reduce local autonomy, this reduction has not been dramatic yet. The constraints on local governments are mainly relevant in financial matters, in which since 2012 state and regional controls on local authorities have significantly increased to ensure the balance and sustainability of local budgets. Currently, the most urgent reforms concern the second tier of local government (provinces), whose contours are not clearly set out either in the Constitution or in the general laws, and the rural municipalities, many of which are continuously losing population and are at risk of disappearing.
Comparative Conclusions
Authors: Steytler Nico
Published: February 2024

This chapter draws comparative conclusion about the role and place of local governments in 16 federal or federal-type countries and explores their relationship with the other orders of government and their impact on the system of federalism as a whole. It seeks to answer the overall question of whether the growth of local government with relative autonomy is changing the shape of federal systems. Local government is increasingly seen as part of the state formation; its status is evolving. In some countries, local government is seen as an integral part of the federated state and recognised as such in the federal constitution. Discrete areas of autonomous decision-making in policy and finances are also emerging. In other countries where the traditional subservient position of local governments to state governments is maintained, and financial self-reliance is leading to greater policy autonomy. The recognition of local government as an order of government—often with direct engagement with the federal government—is the most pronounced in metropolitan governments and in fiscal relations.
Measuring Adolescents’ Life Skills and Values: Method and Results from East Africa
Authors: Ariapa Martin , Pavlovic Masa , Care Esther
Published: February 2024

The goals of the ALiVE initiative, to capture and disseminate estimates of adolescents’ life skills and values at a level that would provide valuable information to ministries of education, guided the development of an assessment tool. The aim was to produce a tool that had the capacity to assess the proficiencies of adolescents in East Africa through a household-based approach. This approach required that the tool could capture these cognitive, interpersonal, and intrapersonal capacities; not rely on knowledge and skills built through formal education; and would be compatible with oral administration of the assessment with participating adolescents. The process of development is described as taking place within these parameters. Results from the assessment of 45,442 adolescents across Kenya, Tanzania, and Uganda are presented following the technical information generated through the test and scale development process. The patterns of results are uniformly similar across each of the education systems, although there are some slight differences in levels of proficiencies. The outcomes provide confidence in the test and scale development processes followed, and in the use of household-based assessment for measurement of life skills and values.
Einleitung
Authors: Probst-Böhm Anja
Published: February 2024

Archäologische Artefakte kann man als Buchstaben oder Wörter verstehen. Interpretiert oder besser verstanden und richtig zusammengesetzt, können sie eine Geschichte über die damaligen Menschen erzählen. Anders als z. B. in der Forensik stehen für die Überprüfung einer Interpretation aber meist nur sehr eingeschränkte Möglichkeiten zur Verfügung.
Typo-chronologische Aufarbeitung der Knochen-, Geweih- und Zahnartefakte
Authors: Probst-Böhm Anja
Published: February 2024

Bei den folgenden Bestimmungen wurden Knochen-, Geweih- und Zahnartefakte ohne Differenzierung insgesamt erfasst. Nagespuren von Kleintieren konnten an keinem der untersuchten Artefakte beobachtet werden und Wurzelfraß konnte nur vereinzelt an den Funden aus den Mineralbodensiedlungen entdeckt werden.
KIF18A inactivates hepatic stellate cells and alleviates liver fibrosis through the TTC3/Akt/mTOR pathway
Authors: Zhang Hao , Xia Tong , Xia Zhijia , Zhou Huaxin , Li Zhipeng , Wang Wei , Zhai Xiangyu , Jin Bin
Published: February 2024

Activation of hepatic stellate cells (HSCs) has been demonstrated to play a pivotal role in the process of liver fibrogenesis. In this study, we observed a decrease in the expression of KIF18A in fibrotic liver tissues compared to healthy liver tissues, which exhibited a negative correlation with the activation of HSCs. To elucidate the molecular mechanisms underlying the involvement of KIF18A, we performed in vitro proliferation experiments and established a CCl4-induced liver fibrosis model. Our results revealed that KIF18A knockdown enhanced HSCs proliferation and reduced HSCs apoptosis in vitro. Mouse liver fibrosis grade was evaluated with Masson’s trichrome and alpha-smooth muscle actin (α-SMA) staining. In addition, the expression of fibrosis markers Col1A1, Stat1, and Timp1 were detected. Animal experiments demonstrated that knockdown of KIF18A could promote liver fibrosis, whereas overexpression of KIF18A alleviated liver fibrosis in a CCl4-induced mouse model. Mechanistically, we found that KIF18A suppressed the AKT/mTOR pathway and exhibited direct binding to TTC3. Moreover, TTC3 was found to interact with p-AKT and could promote its ubiquitination and degradation. Our findings provide compelling evidence that KIF18A enhances the protein binding between TTC3 and p-AKT, promoting TTC3-mediated ubiquitination and degradation of p-AKT. These results refine the current understanding of the mechanisms underlying the pathogenesis of liver fibrosis and may offer new targets for treating this patient population.
Stability of Time-Dependent Motions for Fluid–Rigid Ball Interaction
Authors: Hishida Toshiaki
Published: February 2024

We aim at the stability of time-dependent motions, such as time-periodic ones, of a rigid body in a viscous fluid filling the exterior to it in 3D. The fluid motion obeys the incompressible Navier–Stokes system, whereas the motion of the body is governed by the balance for linear and angular momentum. Both motions are affected by each other at the boundary. Assuming that the rigid body is a ball, we adopt a monolithic approach to deduce $$L^q$$

L
q

–$$L^r$$

L
r

decay estimates of solutions to a non-autonomous linearized system. We then apply those estimates to the full nonlinear initial value problem to find temporal decay properties of the disturbance. Although the shape of the body is not allowed to be arbitrary, the present contribution is the first attempt at analysis of the large time behavior of solutions around nontrivial basic states, that can be time-dependent, for the fluid–structure interaction problem and provides us with a stability theorem which is indeed new even for steady motions under the self-propelling condition or with wake structure.
Genome-wide association and Mendelian randomisation analysis among 30,699 Chinese pregnant women identifies novel genetic and molecular risk factors for gestational diabetes and glycaemic traits
Authors: Zhen Jianxin , Gu Yuqin , Wang Piao , Wang Weihong , Bian Shengzhe , Huang Shujia , Liang Hui , Huang Mingxi , Yu Yan , Chen Qing , Jiang Guozhi , Qiu Xiu , Xiong Likuan , Liu Siyang
Published: February 2024

Aims/hypothesis

Gestational diabetes mellitus (GDM) is the most common disorder in pregnancy; however, its underlying causes remain obscure. This study aimed to investigate the genetic and molecular risk factors contributing to GDM and glycaemic traits.

Methods

We collected non-invasive prenatal test (NIPT) sequencing data along with four glycaemic and 55 biochemical measurements from 30,699 pregnant women during a 2 year period at Shenzhen Baoan Women’s and Children’s Hospital in China. Genome-wide association studies (GWAS) were conducted between genotypes derived from NIPTs and GDM diagnosis, baseline glycaemic levels and glycaemic levels after glucose challenges. In total, 3317 women were diagnosed with GDM, while 19,565 served as control participants. The results were replicated using two independent cohorts. Additionally, we performed one-sample Mendelian randomisation to explore potential causal associations between the 55 biochemical measurements and risk of GDM and glycaemic levels.

Results

We identified four genetic loci significantly associated with GDM susceptibility. Among these, MTNR1B exhibited the highest significance (rs10830963-G, OR [95% CI] 1.57 [1.45, 1.70], p=4.42×10–29), although its effect on type 2 diabetes was modest. Furthermore, we found 31 genetic loci, including 14 novel loci, that were significantly associated with the four glycaemic traits. The replication rates of these associations with GDM, fasting plasma glucose levels and 0 h, 1 h and 2 h OGTT glucose levels were 4 out of 4, 6 out of 9, 10 out of 11, 5 out of 7 and 4 out of 4, respectively. Mendelian randomisation analysis suggested that a genetically regulated higher lymphocytes percentage and lower white blood cell count, neutrophil percentage and absolute neutrophil count were associated with elevated glucose levels and an increased risk of GDM.

Conclusions/interpretation

Our findings provide new insights into the genetic basis of GDM and glycaemic traits during pregnancy in an East Asian population and highlight the potential role of inflammatory pathways in the aetiology of GDM and variations in glycaemic levels.

Data availability

Summary statistics for GDM; fasting plasma glucose; 0 h, 1 h and 2h OGTT; and the 55 biomarkers are available in the GWAS Atlas (study accession no.: GVP000001, https://ngdc.cncb.ac.cn/gwas/browse/GVP000001).

Graphical Abstract
Safety, tolerability and immunogenicity of PRV-101, a multivalent vaccine targeting coxsackie B viruses (CVBs) associated with type 1 diabetes: a double-blind randomised placebo-controlled Phase I trial
Authors: Hyöty Heikki , Kääriäinen Susanna , Laiho Jutta E. , Comer Gail M. , Tian Wei , Härkönen Taina , Lehtonen Jussi P. , Oikarinen Sami , Puustinen Leena , Snyder Michele , León Francisco , Scheinin Mika , Knip Mikael , Sanjuan Miguel
Published: February 2024

Aims/hypothesis

Infection with coxsackie B viruses (CVBs) can cause diseases ranging from mild common cold-type symptoms to severe life-threatening conditions. CVB infections are considered to be prime candidates for environmental triggers of type 1 diabetes. This, together with the significant disease burden of acute CVB infections and their association with chronic diseases other than diabetes, has prompted the development of human CVB vaccines. The current study evaluated the safety and immunogenicity of the first human vaccine designed against CVBs associated with type 1 diabetes in a double-blind randomised placebo-controlled Phase I trial.

Methods

The main eligibility criteria for participants were good general health, age between 18 and 45 years, provision of written informed consent and willingness to comply with all trial procedures. Treatment allocation (PRV-101 or placebo) was based on a computer-generated randomisation schedule and people assessing the outcomes were masked to group assignment. In total, 32 participants (17 men, 15 women) aged 18–44 years were randomised to receive a low (n=12) or high (n=12) dose of a multivalent, formalin-inactivated vaccine including CVB serotypes 1–5 (PRV-101), or placebo (n=8), given by intramuscular injections at weeks 0, 4 and 8 at a single study site in Finland. The participants were followed for another 24 weeks. Safety and tolerability were the primary endpoints. Anti-CVB IgG and virus-neutralising titres were analysed using an ELISA and neutralising plaque reduction assays, respectively.

Results

Among the 32 participants (low dose, n=12; high dose, n=12; placebo, n=8) no serious adverse events or adverse events leading to study treatment discontinuation were observed. Treatment-emergent adverse events considered to be related to the study drug occurred in 37.5% of the participants in the placebo group and 62.5% in the PRV-101 group (injection site pain, headache, injection site discomfort and injection site pruritus being most common). PRV-101 induced dose-dependent neutralising antibody responses against all five CVB serotypes included in the vaccine in both the high- and low-dose groups. Protective titres ≥8 against all five serotypes were seen in >90% of participants over the entire follow-up period.

Conclusions/interpretation

The results indicate that the tested multivalent CVB vaccine is well tolerated and immunogenic, supporting its further clinical development.

Trial registration

ClinicalTrials.gov NCT04690426.

Funding

This trial was funded by Provention Bio, a Sanofi company.

Graphical Abstract
Parametric optimizing of electro-discharge machining for LM25Al/VC composite material machining using deterministic and stochastic methods
Authors: Tolcha Mesay Alemu , Lemu Hirpa Gelgele
Published: February 2024

The electro-discharge machining (EDM) process is investigated using deterministic and stochastic methods to determine and model the effects of process parameters on machining performance. The workpiece utilized for the investigation was an LM25 aluminum alloy reinforced with vanadium carbide (VC), processed through a stir casting technique. EDM process parameters like peak current, discharge voltage, and pulse on-time are considered to analyze material removal rate, electrode wearing rate, and surface roughness. This study applied four multi-criteria decision-making (MCDM) and analytical methodologies to evaluate EDM performance. Then, the MCDM scores were compared using two objective verification mechanisms. In this case, the teaching-learning-based optimization (TLBO) technique delivered the best-desired results relative to the VIKOR, Grey relational grade (GRG), and the response surface method (RSM). Also, the RSM and analytical methods are simpler than the other methods, though they produced nearly identical results as the sophisticated MDCM and deterministic methods.
Pleurotus ostreatus as a model mushroom in genetics, cell biology, and material sciences
Authors: Nakazawa Takehito , Kawauchi Moriyuki , Otsuka Yuitsu , Han Junxian , Koshi Daishiro , Schiphof Kim , Ramírez Lucía , Pisabarro Antonio G. , Honda Yoichi
Published: February 2024

Pleurotus ostreatus, also known as the oyster mushroom, is a popular edible mushroom cultivated worldwide. This review aims to survey recent progress in the molecular genetics of this fungus and demonstrate its potential as a model mushroom for future research. The development of modern molecular genetic techniques and genome sequencing technologies has resulted in breakthroughs in mushroom science. With efficient transformation protocols and multiple selection markers, a powerful toolbox, including techniques such as gene knockout and genome editing, has been developed, and numerous new findings are accumulating in P. ostreatus. These include molecular mechanisms of wood component degradation, sexual development, protein secretion systems, and cell wall structure. Furthermore, these techniques enable the identification of new horizons in enzymology, biochemistry, cell biology, and material science through protein engineering, fluorescence microscopy, and molecular breeding.

Key points

• Various genetic techniques are available in Pleurotus ostreatus.

• P. ostreatus can be used as an alternative model mushroom in genetic analyses.

• New frontiers in mushroom science are being developed using the fungus.
VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway
Authors: Wang Qian , Tang Yuwen , Dai Ang , Li Tiange , Pei Yulin , Zhang Zuo , Hu Xinyue , Chen Tingtao , Chen Qi
Published: February 2024

Ovarian cancer poses a significant threat to women’s health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM’s apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer.

Key points

• This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins

• The engineered bacteria can target and colonize tumor sites in vivo

• VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells

Graphical Abstract
‘Climate Healing Stones’: Common Minerals Offer Substantial Climate Change Mitigation Potential
Authors: Pratt Chris , Mahdi Zainab , El Hanandeh Ali
Published: February 2024

This review proposes that mineral-based greenhouse gas (GHG) mitigation could be developed into a substantial climate change abatement tool. This proposal was evaluated via three objectives: (1) synthesise literature studies documenting the effectiveness of geological minerals at mitigating GHG emissions; (2) quantify, via meta-analysis, GHG magnitudes that could be abated by minerals factoring-in the carbon footprint of the approach; and (3) estimate the global availability of relevant minerals. Several minerals have been effectively harnessed across multiple sectors—including agriculture, waste management and coal mining—to mitigate carbon dioxide/CO2 (e.g., olivine), methane/CH4 (e.g., allophane, gypsum) and nitrous oxide/N2O (e.g., vermiculite) emissions. High surface area minerals offer substantial promise to protect soil carbon, albeit their potential impact here is difficult to quantify. Although mineral-based N2O reduction strategies can achieve gross emission reduction, their application generates a net carbon emission due to prohibitively large mineral quantities needed. By contrast, mineral-based technologies could abate ~9% and 11% of global CO2 and CH4 anthropogenic emissions, respectively. These estimates conservatively only consider options which offer additional benefits to climate change mitigation (e.g., nutrient supply to agricultural landscapes, and safety controls in landfill operations). This multi-benefit aspect is important due to the reluctance to invest in stand-alone GHG mitigation technologies. Minerals that exhibit high GHG mitigation potential are globally abundant. However, their application towards a dedicated global GHG mitigation initiative would entail significant escalation of their current production rates. A detailed cost-benefit analysis and environmental and social footprint assessment is needed to ascertain the strategy’s scale-up potential.
Assessment of water stress impact on olive trees using an accurate determination of the endocarp development
Authors: Sánchez-Piñero Marta , Corell Mireia , de Sosa Laura L. , Moriana Alfonso , Medina-Zurita Noemí , Madejón Engracia , Girón Ignacio , Castro-Valdecantos Pedro , Martín-Palomo María José , Pérez-López David
Published: February 2024

When considering deficit irrigation, the most resistant period to water stress in olive crops is during the pit hardening. However, the determination of this period and the impact that water stress has on its onset or duration have not been clearly established. The aim of this work is to describe the impact of water stress on three processes that determine fruit development: fruit growth, endocarp hardening, and oil accumulation. This experiment was conducted between 2021 and 2022, in a plot with olive trees that were 3 years old at the beginning of the experiment. The young trees were of cv Manzanilla de Sevilla and were planted in a 4 × 1.5 m frame. The treatments were: Control, irrigated close to what is considered the optimum level in which the water status of the crop ensures the absence of water stress; RDI, with a moderate stress during the pit hardening stage; Rainfed and Traditional Rainfed. This latter was included only in 2022 using a 7 × 5 m frame. Traditional Rainfed was included to compare with Rainfed, these were similar in the maximum level of water stress but not in the duration. The fruit growth, oil accumulation, and endocarp hardness were measured for a period of 2 years. The hardness curves fit accurately established Period II which was the one with the fast hardness increases. The water potential was measured periodically on leaves at midday, whereby the minimum and average potential and the stress integral were obtained for each of the periods indicated before using pit hardness measurements. The results suggest that endocarp hardening was the process most resistant to water stress, as it showed very little variation from the seasonal pattern, despite the high levels of stress achieved. The fruit growth process was the most sensitive to water stress, but the recovery was fast in conditions of moderate water stress level. The oil accumulation started slowly during Period II, but its rate increased at the end of the period. This later process was moderately resistant to water stress. However, although the accumulation rate was faster during Period III, it was influenced by the water status during Period II. Cumulative water stress was related with fruit growth and oil accumulation processes. Endocarp development could be useful for determining a/the deficit irrigation period because of its almost constant pattern. These periods would permit water management optimization according to final use of the fruit (oil or table). However, continuous monitoring of water stress would be needed.
Use of class IC antiarrhythmic drugs in patients with structural heart disease and implantable cardioverter defibrillator
Authors: Zylla Maura M. , Wolfes Julian , Schleberger Ruben , Lawin Dennis , Kieser Meinhard , Reinke Florian , Eckardt Lars , Rillig Andreas , Stellbrink Christoph , Thomas Dierk , Frey Norbert , Lugenbiel Patrick
Published: February 2024

Background

Due to suspected pro-arrhythmic effects and increased mortality associated with class-IC antiarrhythmic drugs (AADs) in previous trials, AAD therapy in structural heart disease (SHD) is mainly restricted to amiodarone. In the presence of diagnostic and therapeutic advancements in cardiovascular medicine, it remains unclear if previous studies adequately reflect contemporary patients. In clinical practice, class-IC-AADs are occasionally used in individual cases, particularly in patients with an implantable cardioverter defibrillator (ICD).

Methods

This study retrospectively investigated outcome in ICD-carriers with SHD in whom class-IC-AADs were used as an individualized therapy due to failure, side effects, or unacceptable risk of alternative therapeutic options.

Results

Fifty patients from four tertiary centers were included (median age 48.5 years; 52% female). The most common underlying SHD were dilated (42%) or ischemic cardiomyopathy (26%) (median LVEF = 45%). Indications for AAD were sustained ventricular arrhythmias (VA) (58%), symptomatic premature ventricular contractions (26%), or atrial arrhythmias (16%). Median follow-up was 27.8 months. Freedom from sustained VA was 72%, and freedom from ICD therapy was 80%. In 19 patients (38%), AAD therapy was terminated. The most common reason was insufficient efficacy (n = 8). Pro-arrhythmia was suspected in three patients. Five patients died during follow-up (10.0%), two of cardiovascular cause (4.0%).

Conclusion

In a multicenter cohort of ICD-carriers with SHD, class-IC-AADs were associated with a low rate of pro-arrhythmic effects or cardiovascular mortality. The majority of patients remained free from sustained VA during a follow-up of > 2 years. Further efforts should be made to evaluate the safety of class-IC-AADs in SHD patients receiving contemporary cardiovascular therapy.

Graphical abstract