bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Fe-HMOR with a Preferential Iron Location in the 12-MR Channels for Dimethyl Ether Carbonylation
Authors: Liu Wenrong , Wang Yaquan , Bu Lingzhen , Chu Kailiang , Huang Yitong , Guo Niandong , Qu Liping , Sang Juncai , Su Xuemei , Zhang Xian , Li Yaoning
Published: May 2024

As the Brønsted acid sites in the 8-membered ring (8-MR) of mordenite (MOR) are reported to be the active center for dimethyl ether (DME) carbonylation reaction, it is of great importance to selectively increase the Brønsted acid amount in the 8-MR. Herein, a series of Fe-HMOR was prepared through one-pot hydrothermal synthesis by adding the EDTA–Fe complex into the gel. By combining XRD, FTIR, UV–Vis, Raman and XPS, it was found that the Fe atoms selectively substituted for the Al atoms in the 12-MR channels because of the large size of the EDTA–Fe complex. The NH3-TPD and Py-IR results showed that with the increase in Fe addition from Fe/Si = 0 to 0.02, the Brønsted acid sites derived from Si-OH-Al in the 8-MR first increased and then decreased, with the maximum at Fe/Si = 0.01. The Fe-modified MOR with Fe/Si = 0.01 showed the highest activity in DME carbonylation, which was three times that of HMOR. The TG/DTG results indicated that the carbon deposition and heavy coke formation in the spent Fe-HMOR catalysts were inhibited due to Fe addition. This work provides a practical way to design a catalyst with enhanced catalytic performance.
Effect of Pseudomonas aeruginosa on Corrosion Behavior of X65 Carbon Steel
Authors: Shao Zixuan , Guo Ruiqi , Tang Jianhua , Zhang Xin
Published: May 2024

X65 pipeline steel is widely used in the field of offshore oil and gas exploitation due to its excellent performance. However, due to the complex environment in the ocean, X65 pipeline steel is faced with a great risk of microbial corrosion failure. Therefore, it is of great significance to study the corrosion mechanism of X65 pipeline steel by microorganisms. In this paper, the corrosion effect of Pseudomonas aeruginosa (P. aeruginosa) secreting phenazine compounds on X65 pipeline steel was studied by the weight loss method, biofilm scanning electron microscopy analysis, surface corrosion morphology observation, electrochemical testing and medium pH test corrosion products. The results showed that the inoculation of P. aeruginosa accelerated the corrosion of X65 steel. After knocking out the phzM and phzS genes that regulate the synthesis of PYO, P. aeruginosa can still produce biofilms on the surface of X65 steel consistent with the morphology of wild-type P. aeruginosa, but the corrosion of X65 steel is significantly reduced. It is proved that PYO plays an important role in the corrosion process of P. aeruginosa on steel.
CC-DETR: DETR with Hybrid Context and Multi-Scale Coordinate Convolution for Crowd Counting
Authors: Gu Yanhong , Zhang Tao , Hu Yuxia , Nian Fudong
Published: May 2024

Prevailing crowd counting approaches primarily rely on density map regression methods. Despite wonderful progress, significant scale variations and complex background interference within the same image remain challenges. To address these issues, in this paper we propose a novel DETR-based crowd counting framework called Crowd Counting DETR (CC-DETR), which aims to extend the state-of-the-art DETR object detection framework to the crowd counting task. In CC-DETR, a DETR-like encoder–decoder structure (Hybrid Context DETR, i.e., HCDETR) is proposed to tackle complex visual information by fusing features from hybrid semantic levels through a transformer. In addition, we design a Coordinate Dilated Convolution Module (CDCM) to effectively employ position-sensitive context information in different scales. Extensive experiments on three challenging crowd counting datasets (ShanghaiTech, UCF-QNRF, and NWPU) demonstrate that our model is effective and competitive when compared against SOTA crowd counting models.
The Impact of Missing Continuous Blood Glucose Samples on Machine Learning Models for Predicting Postprandial Hypoglycemia: An Experimental Analysis
Authors: Rehman Najib Ur , Contreras Ivan , Beneyto Aleix , Vehi Josep
Published: May 2024

This study investigates how missing data samples in continuous blood glucose data affect the prediction of postprandial hypoglycemia, which is crucial for diabetes management. We analyzed the impact of missing samples at different times before meals using two datasets: virtual patient data and real patient data. The study uses six commonly used machine learning models under varying conditions of missing samples, including custom and random patterns reflective of device failures and arbitrary data loss, with different levels of data removal before mealtimes. Additionally, the study explored different interpolation techniques to counter the effects of missing data samples. The research shows that missing samples generally reduce the model performance, but random forest is more robust to missing samples. The study concludes that the adverse effects of missing samples can be mitigated by leveraging complementary and informative non-point features. Consequently, our research highlights the importance of strategically handling missing data, selecting appropriate machine learning models, and considering feature types to enhance the performance of postprandial hypoglycemia predictions, thereby improving diabetes management.
Curdepsidone A Induces Intrinsic Apoptosis and Inhibits Protective Autophagy via the ROS/PI3K/AKT Signaling Pathway in HeLa Cells
Authors: Xu Sunjie , Li Zhimin , Xin Xiujuan , An Faliang
Published: May 2024

Among female oncology patients, cervical cancer stands as the fourth most prevalent malignancy, exerting significant impacts on their health. Over 600,000 women received the diagnosis of cervical cancer in 2020, and the illness claimed over 300,000 lives globally. Curdepsidone A, a derivative of depsidone, was isolated from the secondary metabolites of Curvularia sp. IFB-Z10. In this study, we revised the molecular structure of curdepsidone A and investigated the fundamental mechanism of the anti-tumor activity of curdepsidone A in HeLa cells for the first time. The results demonstrated that curdepsidone A caused G0/G1 phase arrest, triggered apoptosis via a mitochondrial apoptotic pathway, blocked the autophagic flux, suppressed the PI3K/AKT pathway, and increased the accumulation of reactive oxygen species (ROS) in HeLa cells. Furthermore, the PI3K inhibitor (LY294002) promoted apoptosis induced by curdepsidone A, while the PI3K agonist (IGF-1) eliminated such an effect. ROS scavenger (NAC) reduced curdepsidone A-induced cell apoptosis and the suppression of autophagy and the PI3K/AKT pathway. In conclusion, our results revealed that curdepsidone A hindered cell growth by causing cell cycle arrest, and promoted cell apoptosis by inhibiting autophagy and the ROS-mediated PI3K/AKT pathway. This study provides a molecular basis for the development of curdepsidone A as a new chemotherapy drug for cervical cancer.
Tensile Properties of a Non-Equiatomic Ni–Co–V Medium Entropy Alloy at Cryogenic Temperature
Authors: Zhou Dawei , Shi Caijuan , Wang Caixia , Sheng Ruixin , Li Weidong , Tong Yang
Published: May 2024

The development of strong and ductile alloys for application in cryogenic temperatures has long been sought after. In this work, we have developed a face-centered cubic Ni10Co56.5V33.5 multi-principal element alloy (MPEA) that exhibits a balanced combination of high strength and good ductility at 77 K, based on the considerations of large local lattice distortion (LLD) and low stacking fault energy. The small-grained Ni10Co56.5V33.5 MPEA exhibits a yield strength of 1400 MPa and an ultimate tensile strength of 1890 MPa, while preserving a good ductility of 23%. Moreover, precession electron diffraction and transmission electron microscopy revealed multiple deformation mechanisms, including wavy dislocations, atypically severely twisted dislocation bands, hierarchical stacking faults, and deformation twins, which are implicated in the alloy’s outstanding mechanical performance. These insights offer a strategic guide for the design of strong and ductile alloys, particularly for utilization in extreme environments.
The Role of Exerkines in Obesity-Induced Disruption of Mitochondrial Homeostasis in Thermogenic Fat
Authors: Shao Hui , Zhang Huijie , Jia Dandan
Published: May 2024

There is a notable correlation between mitochondrial homeostasis and metabolic disruption. In this review, we report that obesity-induced disruption of mitochondrial homeostasis adversely affects lipid metabolism, adipocyte differentiation, oxidative capacity, inflammation, insulin sensitivity, and thermogenesis in thermogenic fat. Elevating mitochondrial homeostasis in thermogenic fat emerges as a promising avenue for developing treatments for metabolic diseases, including enhanced mitochondrial function, mitophagy, mitochondrial uncoupling, and mitochondrial biogenesis. The exerkines (e.g., myokines, adipokines, batokines) released during exercise have the potential to ameliorate mitochondrial homeostasis, improve glucose and lipid metabolism, and stimulate fat browning and thermogenesis as a defense against obesity-associated metabolic diseases. This comprehensive review focuses on the manifold benefits of exercise-induced exerkines, particularly emphasizing their influence on mitochondrial homeostasis and fat thermogenesis in the context of metabolic disorders associated with obesity.
An Intelligent Non-Invasive Blood Pressure Monitoring System Based on a Novel Polyvinylidene Fluoride Piezoelectric Thin Film
Authors: Li Shilin , Zhou Taoyun , Liu Muzhou , Zhao Qiaomei , Liu Yi
Published: May 2024

Hypertension is a common cause of cardiovascular diseases, closely associated with the high mortality and disability rates of cardiovascular diseases such as stroke and coronary heart disease. Therefore, developing a comfortable and sustainable device for monitoring human pulse signals holds practical significance for the prevention and treatment of hypertension and cardiovascular diseases. PVDF flexible pressure sensors possess the characteristics of high sensitivity, good flexibility, and strong biocompatibility, thereby demonstrating extensive application potential in areas such as health monitoring, wearable devices, and electronic skins. This paper focuses on the development of a modified piezoelectric polymer and its application in an intelligent blood pressure monitoring system, demonstrating its outstanding performance and feasibility through a series of experiments. This research provides innovative material choices for the development of intelligent medical devices and offers beneficial guidance for the design and application of future intelligent health monitoring systems.
Development of a Measurement Device for Micro Gas Flowrate Based on Laminar Flow Element with Micro-Curved Surface
Authors: Wang Zixuan , Xu Ya , Liu Tiejun , Huang Zhenwei , Xie Dailiang
Published: May 2024

The laminar flow meter (LFM) boasts several advantages such as no moving parts, a wide range ratio, high measurement accuracy, quick dynamic response, etc., and is a promising technology for micro gas flow measurement. In order to explore the influence of different curvature radii on curved surface gap LFM, three curved structures with different curvature radii were designed. The computational fluid dynamics method is applied to simulate the flow feature of three structures. The simulated velocity cloud and pressure distribution show that the larger the curvature radius, the more stable the flow of gas medium. The relationship between differential pressure and volume flow was obtained through the test within a flow range of 0~540 sccm. Regression analysis revealed that the volume flow measured by the curved surface LFM had a high linear relationship with the differential pressure. Experimental findings indicate that differential pressure of the structure with a curvature radius of 2 mm was greater than that of other two structures (curvature radius of 6 mm and 3 mm) at the same point. This indicates that adding the number of surfaces can effectively increase the pressure loss, so as to obtain a larger range ratio, but will increase the measurement error.
Bacillus siamensis Improves the Immune Status and Intestinal Health of Weaned Piglets by Improving Their Intestinal Microbiota
Authors: Liu Huawei , Liu Xinyu , Liu Haiyang , Tang Jiaqi , He Wei , Xu Tianqi , Cheng Baojing , Shi Baoming , Han Jianchun
Published: May 2024

Previous studies on the early interference of gut microbiota by Bacillus siamensis (B. siamensis) in weaned piglets are rarely reported, and the present trial is a preliminary study. This experiment was conducted to investigate the effects of B. siamensis supplementation on the growth performance, serum biochemistry, immune response, fecal short-chain fatty acids and microbiota of weaned piglets. Sixty weaned piglets were randomly divided into a control group (CON) and a B. siamensis group (BS), which were fed a basal diet and the basal diet supplemented with 5 × 1010 CFU B. siamensis per kg, respectively. Each group had 3 replicates and 10 piglets per replicate. The trial lasted for 28 days. The results showed that B. siamensis significantly increased the serum growth hormone (GH) and insulin-like growth factor (IGF) in piglets. Compared with the CON group, the levels of serum immunoglobulin and inflammatory factors in the BS group were significantly improved. In addition, the serum concentrations of zonulin and endotoxin (ET) in the BS group were lower. The dietary addition of B. siamensis significantly increased fecal short-chain fatty acid (SCFA) levels in piglets. Notably, B. siamensis improved the microbial composition by increasing beneficial genera, including Weissella, Lachnospiraceae_NK4A136_group and Bifidobacterium, and decreasing pathogenic genera, including Pantoea, Fusobacterium and Gemella, in piglet feces. Correlation analysis showed that the benefits of dietary B. siamensis supplementation were closely related to its improved microbial composition. In summary, the addition of B. siamensis can improve the immunity function, inflammatory response, gut permeability and SCFA levels of weaned piglets, which may be achieved through the improvement of their microbiota.
Rapid Identification of Brucella Genus and Species In Silico and On-Site Using Novel Probes with CRISPR/Cas12a
Authors: Zhang Yan , Lyu Yufei , Wang Dongshu , Feng Meijie , Shen Sicheng , Zhu Li , Pan Chao , Zai Xiaodong , Wang Shuyi , Guo Yan , Yu Shujuan , Gong Xiaowei , Chen Qiwei , Wang Hengliang , Wang Yuanzhi , Liu Xiankai
Published: May 2024

Human brucellosis caused by Brucella is a widespread zoonosis that is prevalent in many countries globally. The high homology between members of the Brucella genus and Ochrobactrum spp. often complicates the determination of disease etiology in patients. The efficient and reliable identification and distinction of Brucella are of primary interest for both medical surveillance and outbreak purposes. A large amount of genomic data for the Brucella genus was analyzed to uncover novel probes containing single-nucleotide polymorphisms (SNPs). GAMOSCE v1.0 software was developed based on the above novel eProbes. In conjunction with clinical requirements, an RPA-Cas12a detection method was developed for the on-site determination of B. abortus and B. melitensis by fluorescence and lateral flow dipsticks (LFDs). We demonstrated the potential of these probes for rapid and accurate detection of the Brucella genus and five significant Brucella species in silico using GAMOSCE. GAMOSCE was validated on different Brucella datasets and correctly identified all Brucella strains, demonstrating a strong discrimination ability. The RPA-Cas12a detection method showed good performance in detection in clinical blood samples and veterinary isolates. We provide both in silico and on-site methods that are convenient and reliable for use in local hospitals and public health programs for the detection of brucellosis.
Microscopic Image Dataset with Segmentation and Detection Labels for Microplastic Analysis in Sewage: Enhancing Research and Environmental Monitoring
Authors: Lee Gwanghee , Jung Jaeheon , Moon Sangjun , Jung Jihyun , Jhang Kyoungson
Published: May 2024

We introduce a novel microscopic image dataset augmented with segmentation and detection labels specifically designed for microplastic analysis in sewage environments. Recognizing the increasing concern over microplastics—particles of synthetic polymers smaller than 5 mm—and their detrimental effects on marine ecosystems and human health, our research focuses on enhancing detection and analytical methodologies through advanced computer vision and deep learning techniques. The dataset comprises high-resolution microscopic images of microplastics collected from sewage, meticulously labeled for both segmentation and detection tasks, aiming to facilitate accurate and efficient identification and quantification of microplastic pollution. In addition to dataset development, we present example deep learning models optimized for segmentation and detection of microplastics within complex sewage samples. The models demonstrate significant potential in automating the analysis of microplastic contamination, offering a scalable solution to environmental monitoring challenges. Furthermore, we ensure the accessibility and reproducibility 12 of our research by making the dataset and model codes publicly available, accompanied by detailed 13 documentation on GitHub and LabelBox.
Isolation of Intestinal Macrophage Subpopulations for High-Quality Total RNA Purification in Zebrafish
Authors: Del Río-Jay Yalén , Barthelaix Audrey , Reyes-Martínez Cristian , Duperray Christophe , Solis-Cascante Camila J. , Hidalgo Yessia , Luz-Crawford Patricia , Djouad Farida , Feijoo Carmen G.
Published: May 2024

Intestinal macrophages have been poorly studied in fish, mainly due to the lack of specific molecular markers for their identification and isolation. To address this gap, using the zebrafish Tg(mpeg1:EGFP) transgenic line, we developed a fluorescence-activated cell sorting strategy (FACS) that allows us to isolate different intestinal macrophage subpopulations, based on GFP expression and morphological differences. Also, we achieved the purification of high-quality total RNA from each population to perform transcriptomic analysis. The complete strategy comprises three steps, including intestine dissection and tissue dissociation, the isolation of each intestinal macrophage population via FACS, and the extraction of total RNA. To be able to characterize molecularly different macrophage subpopulations and link them to their functional properties will allow us to unravel intestinal macrophage biology.
Direct Imaging of Radiation-Sensitive Organic Polymer-Based Nanocrystals at Sub-Ångström Resolution
Authors: Carlino Elvio , Taurino Antonietta , Hasa Dritan , Bučar Dejan-Krešimir , Polentarutti Maurizio , Chinchilla Lidia E. , Calvino Gamez Josè J.
Published: May 2024

Seeing the atomic configuration of single organic nanoparticles at a sub-Å spatial resolution by transmission electron microscopy has been so far prevented by the high sensitivity of soft matter to radiation damage. This difficulty is related to the need to irradiate the particle with a total dose of a few electrons/Å2, not compatible with the electron beam density necessary to search the low-contrast nanoparticle, to control its drift, finely adjust the electron-optical conditions and particle orientation, and finally acquire an effective atomic-resolution image. On the other hand, the capability to study individual pristine nanoparticles, such as proteins, active pharmaceutical ingredients, and polymers, with peculiar sensitivity to the variation in the local structure, defects, and strain, would provide advancements in many fields, including materials science, medicine, biology, and pharmacology. Here, we report the direct sub-ångström-resolution imaging at room temperature of pristine unstained crystalline polymer-based nanoparticles. This result is obtained by combining low-dose in-line electron holography and phase-contrast imaging on state-of-the-art equipment, providing an effective tool for the quantitative sub-ångström imaging of soft matter.
Magnetic-Dielectric Cantilevers for Atomic Force Microscopy
Authors: Sanchez-Seguame Gala , Avalos-Sanchez Hugo , Eduardo Lugo Jesus , Murillo-Bracamontes Eduardo Antonio , Palomino-Ovando Martha Alicia , Hernández-Cristobal Orlando , Gervacio-Arciniega José Juan , Toledo-Solano Miller
Published: May 2024

Atomic force microscopy (AFM) is a technique that relies on detecting forces at the nanonewton scale. It involves using a cantilever with a tiny tip at one end. This tip interacts with the short- and long-range forces of material surfaces. These cantilevers are typically manufactured with Si or Si3N4 and synthesized using a lithography technique, which implies a high cost. On the other hand, through simple chemical methods, it is possible to synthesize a magneto-dielectric composite made up of artificial SiO2 opals infiltrated with superparamagnetic nanoparticles of Fe3O4. From these materials, it is possible to obtain tipless cantilevers that can be used in AFM analysis. Tipless cantilevers are an alternative tool in nanoscale exploration, offering a versatile approach to surface analysis. Unlike traditional AFM probes, tipless versions eliminate the challenges associated with tip wear, ensuring prolonged stability during measurements. This makes tipless AFM particularly valuable for imaging delicate or soft samples, as it prevents sample damage and provides precise measurements of topography and mechanical and electromechanical properties. This study presents the results of the characterization of known surfaces using magneto-dielectric cantilevers and commercial cantilevers based on Si. The characterization will be carried out through contact and non-contact topography measurements.
Improvement of Post-Surgery Constipation in Patients with Fractures by Lactobacillus rhamnosus JYLR-127: A Single-Blind Randomized Controlled Trial
Authors: Han Yiyang , Zhou Yunlong , Xu Xuan , Chen Shen , Zhang Shuwei , Jiang Nan , Liu Zhiqiang , Zhang Junyu , Luo Zhaowei , Zhang Xinfeng , Hao Liang , Chen Tingtao
Published: May 2024

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.
Fucoidan Improves D-Galactose-Induced Cognitive Dysfunction by Promoting Mitochondrial Biogenesis and Maintaining Gut Microbiome Homeostasis
Authors: Xu Yan , Xue Meilan , Li Jing , Ma Yiqing , Wang Yutong , Zhang Huaqi , Liang Hui
Published: May 2024

Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.
Effects of Saponins on Lipid Metabolism: The Gut–Liver Axis Plays a Key Role
Authors: Cao Shixi , Liu Mengqi , Han Yao , Li Shouren , Zhu Xiaoyan , Li Defeng , Shi Yinghua , Liu Boshuai
Published: May 2024

Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders affecting the health of the organism and inducing the occurrence of diseases. Saponins, as biologically active substances present in plants, have lipid-lowering, inflammation-reducing, and anti-atherosclerotic effects. Saponins are thought to be involved in the regulation of lipid metabolism in the body; it suppresses the appetite and, thus, reduces energy intake by modulating pro-opiomelanocortin/Cocaine amphetamine regulated transcript (POMC/CART) neurons and neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus, the appetite control center. Saponins directly activate the AMP-activated protein kinase (AMPK) signaling pathway and related transcriptional regulators such as peroxisome-proliferator-activated-receptors (PPAR), CCAAT/enhancer-binding proteins (C/EBP), and sterol-regulatory element binding proteins (SREBP) increase fatty acid oxidation and inhibit lipid synthesis. It also modulates gut–liver interactions to improve lipid metabolism by regulating gut microbes and their metabolites and derivatives—short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine (TMA), lipopolysaccharide (LPS), et al. This paper reviews the positive effects of different saponins on lipid metabolism disorders, suggesting that the gut–liver axis plays a crucial role in improving lipid metabolism processes and may be used as a therapeutic target to provide new strategies for treating lipid metabolism disorders.
Obesity Prevalence and Its Impact on Maternal and Neonatal Outcomes among Pregnant Women: A Retrospective Cross-Sectional Study Design
Authors: AlAnnaz Wejdan , Gouda Amel , Abou El-Soud Faiza , Alanazi Mona
Published: May 2024

Background: The escalating prevalence of obesity in women of reproductive age raises concerns about its impact on maternal and fetal health during pregnancy. This study aimed to thoroughly assess how obesity affects pregnancy and neonatal outcomes among Saudi pregnant women. Methods: In a retrospective cross-sectional study, we analyzed 8426 pregnant women who delivered at King Fahad National Guard Hospital in Riyadh in 2021. Of these, 3416 had obesity, and 341 of them, meeting the inclusion criteria, were selected. Maternal and neonatal outcomes were compiled using a structured questionnaire and extracted from the hospital’s “Best Care” data-based registration system. Results: The findings highlighted that 40.5% of pregnant women were classified as obese, with almost half falling into obesity class II based on BMI. Obesity correlated significantly with adverse maternal outcomes like gestational diabetes and increased rates of cesarean deliveries. Additionally, maternal obesity was linked to unfavorable fetal outcomes, including higher rates of newborn intensive care unit admissions, lower APGAR scores at 1 min, and a greater likelihood of macrosomia. Conclusions: This study underscores the important impact of maternal obesity on both maternal and fetal health during pregnancy. Addressing this high-risk condition demands targeted educational programs for women of reproductive age focusing on BMI control, dietary adjustments, and lifestyle modifications to mitigate obesity-related complications during pregnancy.
Sensitivity Assessment of a Multiplex and Real-Time PCR Protocols for the Detection of Malaria in External Quality Control Samples in the Malaria Reference Center in Greece
Authors: Tegos Nikolaos , Goumenopoulos Christos , Mpimpa Anastasia , Papavasilopoulos Vasilios , Beleri Stavroula , Patsoula Eleni
Published: May 2024

Background: Accurate malaria diagnosis constitutes a challenging task, necessitating the need for the implementation of targeted and effective diagnostic tools. The purpose of the current study was to evaluate the effectiveness of two different molecular methodologies in terms of sensitivity for the detection of External Quality Assessment (EQA) Plasmodium samples. Methods: A total of 104 lyophilized blood samples from 14 different UK-NEQAS (National External Quality Assessment Site) (2016–2021) and eight WHO-NEQAS distributions (2017–2020) were analyzed. An in-house multiplex PCR protocol, followed by single target real-time PCR protocols for all five Plasmodium species, was implemented. Results: The multiplex PCR had a success rate of 10/16 and 20/28 for P. vivax and P. falciparum species, respectively. On the other hand, the respective results for real-time PCR had a success rate of 13/16 (P. vivax), 28/28 (P. falciparum), 5/8 (P. malariae), 8/10 (P. ovale), and 10/14 (P. knowlesi). Plasmodium falciparum samples displayed the highest sensitivity of detection, 0.02 parasites/μL. Plasmodium vivax samples displayed a 0.1 parasites/μL cutoff value, greater than the respective value for whole blood samples, while P. ovale species displayed a respective cutoff value of 0.05 parasites/μL. Due to the limited number of tested samples, data obtained for P. malariae and P. knowlesi species samples were inconclusive. Conclusions: Real-time PCR comprises a credible molecular methodology in terms of sensitivity assessment and detection of low parasitemia levels of Plasmodium sp. in EQA lyophilized blood samples.
New Thiazolidine-4-One Derivatives as SARS-CoV-2 Main Protease Inhibitors
Authors: Messore Antonella , Malune Paolo , Patacchini Elisa , Madia Valentina Noemi , Ialongo Davide , Arpacioglu Merve , Albano Aurora , Ruggieri Giuseppe , Saccoliti Francesco , Scipione Luigi , Tramontano Enzo , Canton Serena , Corona Angela , Scognamiglio Sante , Paulis Annalaura , Suleiman Mustapha , Al-Maqtari Helmi Mohammed , Abid Fatma Mohamed A. , Kawsar Sarkar M. A. , Sankaranarayanan Murugesan , Di Santo Roberto , Esposito Francesca , Costi Roberta
Published: May 2024

It has been more than four years since the first report of SARS-CoV-2, and humankind has experienced a pandemic with an unprecedented impact. Moreover, the new variants have made the situation even worse. Among viral enzymes, the SARS-CoV-2 main protease (Mpro) has been deemed a promising drug target vs. COVID-19. Indeed, Mpro is a pivotal enzyme for viral replication, and it is highly conserved within coronaviruses. It showed a high extent of conservation of the protease residues essential to the enzymatic activity, emphasizing its potential as a drug target to develop wide-spectrum antiviral agents effective not only vs. SARS-CoV-2 variants but also against other coronaviruses. Even though the FDA-approved drug nirmatrelvir, a Mpro inhibitor, has boosted the antiviral therapy for the treatment of COVID-19, the drug shows several drawbacks that hinder its clinical application. Herein, we report the synthesis of new thiazolidine-4-one derivatives endowed with inhibitory potencies in the micromolar range against SARS-CoV-2 Mpro. In silico studies shed light on the key structural requirements responsible for binding to highly conserved enzymatic residues, showing that the thiazolidinone core acts as a mimetic of the Gln amino acid of the natural substrate and the central role of the nitro-substituted aromatic portion in establishing π-π stacking interactions with the catalytic His-41 residue.
Enhanced Anti-Inflammatory Activity of Tilianin Based on the Novel Amorphous Nanocrystals
Authors: Sun Min , Guo Mengran , He Zhongshan , Luo Yaoyao , He Xi , Huang Chuansheng , Yuan Yong , Zhao Yunli , Song Xiangrong , Wang Xinchun
Published: May 2024

Tilianin (Til), a flavonoid glycoside, is well-known for its therapeutic promise in treating inflammatory disorders. Its poor water solubility and permeability limit its clinical applicability. In order to overcome these restrictions, an antisolvent precipitation and ultrasonication technique was used to prepare amorphous tilianin nanocrystals (Til NCs). We have adjusted the organic solvents, oil-to-water ratio, stabilizer composition, and ultrasonic power and time by combining single-factor and central composite design (CCD) methodologies. The features of Til NCs were characterized using powder X-ray diffraction (PXRD), scanning calorimetry (DSC), and transmission electron microscopy (TEM). Specifically, the optimized Til NCs were needle-like with a particle size ranging from 90 to 130 nm. PVA (0.3%, w/v) and TPGS (0.08%, w/v) stabilized them well. For at least two months, these Til NCs stayed amorphous and showed an impressive stability at 4 °C and 25 °C. Remarkably, Til NCs dissolved almost 20 times faster in simulated intestinal fluid (SIF) than they did in crude Til. In RAW264.7 cells, Til NCs also showed a better cellular absorption as well as safety and protective qualities. Til NCs were shown to drastically lower reactive oxygen species (ROS), TNF-α, IL-1β, and IL-6 in anti-inflammatory experiments, while increasing IL-10 levels and encouraging M1 macrophages to adopt the anti-inflammatory M2 phenotype. Our results highlight the potential of amorphous Til NCs as a viable approach to improve Til’s anti-inflammatory effectiveness, solubility, and dissolving rate.
Poly(acrylic acid)/Poly(vinyl alcohol) Microarray Patches for Continuous Transdermal Delivery of Levodopa and Carbidopa: In Vitro and In Vivo Studies
Authors: Li Yaocun , Vora Lalitkumar K. , Wang Jiawen , Sabri Akmal Hidayat Bin , Graham Andrew , McCarthy Helen O. , Donnelly Ryan F.
Published: May 2024

Levodopa (LD) has been the most efficacious medication and the gold standard therapy for Parkinson’s disease (PD) for decades. However, its long-term administration is usually associated with motor complications, which are believed to be the result of the fluctuating pharmacokinetics of LD following oral administration. Duodopa® is the current option to offer a continuous delivery of LD and its decarboxylase inhibitor carbidopa (CD); however, its administration involves invasive surgical procedures, which could potentially lead to lifelong complications, such as infection. Recently, dissolving microarray patches (MAPs) have come to the fore as an alternative that can bypass the oral administration route in a minimally invasive way. This work explored the potential of using dissolving MAPs to deliver LD and CD across the skin. An acidic polymer poly(acrylic acid) (PAA) was used in the MAP fabrication to prevent the potential oxidation of LD at neutral pH. The drug contents of LD and CD in the formulated dissolving MAPs were 1.82 ± 0.24 and 0.47 ± 0.04 mg/patch, respectively. The in vivo pharmacokinetic study using female Sprague–Dawley® rats (Envigo RMS Holding Corp, Bicester, UK) demonstrated a simultaneous delivery of LD and CD and comparable AUC values between the dissolving MAPs and the oral LD/CD suspension. The relative bioavailability for the dissolving MAPs was calculated to be approximately 37.22%. Accordingly, this work highlights the use of dissolving MAPs as a minimally invasive approach which could potentially bypass the gastrointestinal pathway and deliver both drugs continuously without surgery.
Therapeutic Drug Monitoring and Biomarkers; towards Better Dosing of Antimicrobial Therapy
Authors: Wehbe Eman , Patanwala Asad E. , Lu Christine Y. , Kim Hannah Yejin , Stocker Sophie L. , Alffenaar Jan-Willem C.
Published: May 2024

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research.
Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets
Authors: Sandler Topelius Niklas , Shokraneh Farnaz , Bahman Mahsa , Lahtinen Julius , Hassinen Niko , Airaksinen Sari , Verma Soumya , Hrizanovska Ludmila , Lass Jana , Paaver Urve , Tähnas Janika , Kern Catharina , Lagarce Frederic , Fenske Dominic , Malik Julia , Scherliess Holger , Cruz Sara P. , Paulsson Mattias , Dekker Jan , Kammonen Katja , Rautamo Maria , Lück Hendrik , Pierrot Antoine , Stareprawo Stephanie , Tubic-Grozdanis Marija , Zibolka Stefanie , Lösch Uli , Jeske Martina , Griesser Ulrich , Hummer Karin , Thalmeier Andreas , Harjans Anna , Kruse Alexander , Heimke-Brinck Ralph , Khoukh Karim , Bruno Fabien
Published: May 2024

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.
Suitable Promoter for DNA Vaccination Using a pDNA Ternary Complex
Authors: Kurosaki Tomoaki , Nakamura Hiroki , Sasaki Hitoshi , Kodama Yukinobu
Published: May 2024

In this study, we evaluated the effect of several promoters on the transfection activity and immune-induction efficiency of a plasmid DNA (pDNA)/polyethylenimine/γ-polyglutamic acid complex (pDNA ternary complex). Model pDNAs encoding firefly luciferase (Luc) were constructed with several promoters, such as simian virus 40 (SV40), eukaryotic elongation factor 1 alpha (EF1), cytomegalovirus (CMV), and chicken beta actin hybrid (CBh) (pSV40-Luc, pEF1-Luc, pCMV-Luc, and pCBh-Luc, respectively). Four types of pDNA ternary complexes, each with approximately 145-nm particle size and −30-mV ζ-potential, were stably constructed. The pDNA ternary complex containing pSV40-Luc showed low gene expression, but the other complexes containing pEF1-Luc, pCMV-Luc, and pCBh-Luc showed high gene expression in DC2.4 cells and spleen after intravenous administration. After immunization using various pDNA encoding ovalbumin (OVA) such as pEF1-OVA, pCMV-OVA, and pCBh-OVA, only the pDNA ternary complex containing pCBh-OVA showed significant anti-OVA immunoglobulin G (IgG) induction. In conclusion, our results showed that the CBh promoter is potentially suitable for use in pDNA ternary complex-based DNA vaccination.
CRISPR/Cas9-Mediated Knockout of the Lycopene ε-Cyclase for Efficient Astaxanthin Production in the Green Microalga Chlamydomonas reinhardtii
Authors: Kneip Jacob Sebastian , Kniepkamp Niklas , Jang Junhwan , Mortaro Maria Grazia , Jin EonSeon , Kruse Olaf , Baier Thomas
Published: May 2024

Carotenoids are valuable pigments naturally occurring in all photosynthetic plants and microalgae as well as in selected fungi, bacteria, and archaea. Green microalgae developed a complex carotenoid profile suitable for efficient light harvesting and light protection and harbor great capacity for carotenoid production through the substantial power of the endogenous 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Previous works established successful genome editing and induced significant changes in the cellular carotenoid content in Chlamydomonas reinhardtii. This study employs a tailored carotenoid pathway for engineered bioproduction of the valuable ketocarotenoid astaxanthin. Functional knockout of lycopene ε-cyclase (LCYE) and non-homologous end joining (NHEJ)-based integration of donor DNA at the target site inhibit the accumulation of α-carotene and consequently lutein and loroxanthin, abundant carotenoids in C. reinhardtii without changes in cellular fitness. PCR-based screening indicated that 4 of 96 regenerated candidate lines carried (partial) integrations of donor DNA and increased ß-carotene as well as derived carotenoid contents. Iterative overexpression of CrBKT, PacrtB, and CrCHYB resulted in a 2.3-fold increase in astaxanthin accumulation in mutant ΔLCYE#3 (1.8 mg/L) compared to the parental strain UVM4, which demonstrates the potential of genome editing for the design of a green cell factory for astaxanthin bioproduction.
Recent Advances in Studies of Genomic DNA Methylation and Its Involvement in Regulating Drought Stress Response in Crops
Authors: Fan Youfang , Sun Chao , Yan Kan , Li Pengcheng , Hein Ingo , Gilroy Eleanor M. , Kear Philip , Bi Zhenzhen , Yao Panfeng , Liu Zhen , Liu Yuhui , Bai Jiangping
Published: May 2024

As global arid conditions worsen and groundwater resources diminish, drought stress has emerged as a critical impediment to plant growth and development globally, notably causing declines in crop yields and even the extinction of certain cultivated species. Numerous studies on drought resistance have demonstrated that DNA methylation dynamically interacts with plant responses to drought stress by modulating gene expression and developmental processes. However, the precise mechanisms underlying these interactions remain elusive. This article consolidates the latest research on the role of DNA methylation in plant responses to drought stress across various species, focusing on methods of methylation detection, mechanisms of methylation pattern alteration (including DNA de novo methylation, DNA maintenance methylation, and DNA demethylation), and overall responses to drought conditions. While many studies have observed significant shifts in genome-wide or gene promoter methylation levels in drought-stressed plants, the identification of specific genes and pathways involved remains limited. This review aims to furnish a reference for detailed research into plant responses to drought stress through epigenetic approaches, striving to identify drought resistance genes regulated by DNA methylation, specific signaling pathways, and their molecular mechanisms of action.
Plant Biostimulants Enhance Tomato Resilience to Salinity Stress: Insights from Two Greek Landraces
Authors: Ntanasi Theodora , Karavidas Ioannis , Spyrou George P. , Giannothanasis Evangelos , Aliferis Konstantinos A. , Saitanis Costas , Fotopoulos Vasileios , Sabatino Leo , Savvas Dimitrios , Ntatsi Georgia
Published: May 2024

Salinity, one of the major abiotic stresses in plants, significantly hampers germination, photosynthesis, biomass production, nutrient balance, and yield of staple crops. To mitigate the impact of such stress without compromising yield and quality, sustainable agronomic practices are required. Among these practices, seaweed extracts (SWEs) and microbial biostimulants (PGRBs) have emerged as important categories of plant biostimulants (PBs). This research aimed at elucidating the effects on growth, yield, quality, and nutrient status of two Greek tomato landraces (‘Tomataki’ and ‘Thessaloniki’) following treatments with the Ascophyllum nodosum seaweed extract ‘Algastar’ and the PGPB ‘Nitrostim’ formulation. Plants were subjected to bi-weekly applications of biostimulants and supplied with two nutrient solutions: 0.5 mM (control) and 30 mM NaCl. The results revealed that the different mode(s) of action of the two PBs impacted the tolerance of the different landraces, since ‘Tomataki’ was benefited only from the SWE application while ‘Thessaloniki’ showed significant increase in fruit numbers and average fruit weight with the application of both PBs at 0.5 and 30 mM NaCl in the root zone. In conclusion, the stress induced by salinity can be mitigated by increasing tomato tolerance through the application of PBs, a sustainable tool for productivity enhancement, which aligns well with the strategy of the European Green Deal.
Liquid Crystal Orientation and Shape Optimization for the Active Response of Liquid Crystal Elastomers
Authors: Barrera Jorge Luis , Cook Caitlyn , Lee Elaine , Swartz Kenneth , Tortorelli Daniel
Published: May 2024

Liquid crystal elastomers (LCEs) are responsive materials that can undergo large reversible deformations upon exposure to external stimuli, such as electrical and thermal fields. Controlling the alignment of their liquid crystals mesogens to achieve desired shape changes unlocks a new design paradigm that is unavailable when using traditional materials. While experimental measurements can provide valuable insights into their behavior, computational analysis is essential to exploit their full potential. Accurate simulation is not, however, the end goal; rather, it is the means to achieve their optimal design. Such design optimization problems are best solved with algorithms that require gradients, i.e., sensitivities, of the cost and constraint functions with respect to the design parameters, to efficiently traverse the design space. In this work, a nonlinear LCE model and adjoint sensitivity analysis are implemented in a scalable and flexible finite element-based open source framework and integrated into a gradient-based design optimization tool. To display the versatility of the computational framework, LCE design problems that optimize both the material, i.e., liquid crystal orientation, and structural shape to reach a target actuated shapes or maximize energy absorption are solved. Multiple parameterizations, customized to address fabrication limitations, are investigated in both 2D and 3D. The case studies are followed by a discussion on the simulation and design optimization hurdles, as well as potential avenues for improving the robustness of similar computational frameworks for applications of interest.