bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between the Platelet to White Blood Cell Ratio and Chronic Kidney Disease in an Aging Population: A Four-Year Follow-Up Study
Authors: Xiong Yang , Zhong Qian , Zhang Yangchang , Qin Feng , Yuan Jiuhong
Published: November 2023

Introduction: The platelet to white blood cell ratio (PWR) has been reported to be a prognostic factor for some diseases, such as subarachnoid hemorrhage. However, the association between the PWR and chronic kidney disease (CKD) remains unknown. To investigate the cross-sectional and longitudinal association between the PWR and CKD, this study was performed. Methods: This study used datasets from a national prospective cohort in China (China Health and Retirement Longitudinal Study). A retrospective cohort from 2011 to 2015 was constructed. The PWR was stratified as a categorical variable according to tertiles (T1–T3 groups). CKD was defined as an estimated glomerular filtration rate < 60 mL min−1/1.73/m2. Univariate and multivariate logistic regressions and restricted cubic spline regression were adopted to assess the linear and non-linear association between the PWR and CKD. Propensity score matching was used to balance the discrepancies between covariates. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were interpolated using random forest. The PWR was also stratified according to the median and quartiles as sensitivity analyses. Results: A total of 8600 participants were included in this study. In the full model, the odds ratios (ORs) of prevalent CKD were 0.78 (95% CI = 0.62–0.97, p < 0.05) for the T2 group and 0.59 (95% CI = 0.46–0.76, p < 0.001) for the T3 group. There were significant interactive effects of marital status and smoking in the PWR–CKD association (both p for interaction < 0.05). An L-shaped, non-linear association was detected between the PWR and prevalent CKD in the overall population, participants ≥ 60 years, and females subgroups (all p for non-linear < 0.05). All sensitivity analyses supported the negative association between the PWR and prevalent CKD. In the 2011–2015 follow-up cohort, the ORs of incident CKD were 0.73 (95% CI = 0.49–1.08, p > 0.05) and 0.31 (95% CI = 0.18–0.51, p < 0.001) for the T2 and T3 groups, respectively, in the full model. Conclusions: A high PWR is associated with a reduced risk of prevalent and incident CKD. The PWR may serve as a predictor for CKD, facilitating the early identification and intervention of kidney function decline.
Correction: Dufvenberg et al. Six-Month Results on Treatment Adherence, Physical Activity, Spinal Appearance, Spinal Deformity, and Quality of Life in an Ongoing Randomised Trial on Conservative Treatment for Adolescent Idiopathic Scoliosis (CONTRAIS). J. Clin. Med. 2021, 10, 4967
Authors: Dufvenberg Marlene , Diarbakerli Elias , Charalampidis Anastasios , Öberg Birgitta , Tropp Hans , Aspberg Ahl Anna , Möller Hans , Gerdhem Paul , Abbott Allan
Published: November 2023

In the original publication [...]
Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism
Authors: Sala Carla , Rescaldani Marta , Gherbesi Elisa , Bolla Gianni , Cuspidi Cesare , Ruscica Massimiliano , Carugo Stefano
Published: November 2023

Background and aim: Nitric oxide inhibits platelet aggregation by increasing the second messenger cyclic guanosine-3′,5′-monophosphate (cGMP) through the activation of soluble guanylyl cyclase in target cells. Within this context, the oxidative stress associated with the aldosterone excess impairs the nitric oxide availability. Thus, the aim of the present study was to assess the impact of chronic aldosterone excess on the platelet nitric oxide/cGMP pathway in humans. Methods: The levels of cGMP were evaluated in platelets of male patients, 12 with primary aldosteronism (PA) and 32 with uncomplicated essential hypertension (EH), matched for age and blood pressure (BP) values. Results: PA and EH patients were 52.8 ± 3 years old and 51.6 ± 1.6 years old, respectively. Systolic and diastolic BP were 158 ± 5.0 mmHg and 105.9 ± 2.3 mmHg in PA and did not differ compared to EH patients (156.6 ± 2.4 mmHg and 104.7 ± 1.2 mmHg). Mean aldosterone levels were significantly higher in PA (25.5 ± 8.8 ng/dL) compared toEH (8.11 ± 0.73 ng/dL), whereas potassium was significantly lower in PA (3.52 ± 0.18 mEq/L) compared to EH (4.08 ± 0.04 mEq/L). Aldosterone and potassium were inversely related (r = −0.49, p = 0.0006) in the whole study population (n = 44). Platelet cGMP was significantly lower in PA (5.1 ± 0.36 pM/109 cells) than in EH (7.1 ± 0.53 pM/109 cells), and in the entire study cohort, it was directly related to plasma potassium (r = 0.43, p = 0.0321). Conclusions: These results show an impairment of nitric oxide/cGMP signaling in platelets of PA patients. This effect is likely related to the potassium-depleting effect of chronic aldosterone excess. Future studies are needed to understand whether the platelet nitric oxide/cGMP system is involved in the atherothrombotic events in these patients.
The Use of Artificial Intelligence for the Classification of Craniofacial Deformities
Authors: Kuehle Reinald , Ringwald Friedemann , Bouffleur Frederic , Hagen Niclas , Schaufelberger Matthias , Nahm Werner , Hoffmann Jürgen , Freudlsperger Christian , Engel Michael , Eisenmann Urs
Published: November 2023

Positional cranial deformities are a common finding in toddlers, yet differentiation from craniosynostosis can be challenging. The aim of this study was to train convolutional neural networks (CNNs) to classify craniofacial deformities based on 2D images generated using photogrammetry as a radiation-free imaging technique. A total of 487 patients with photogrammetry scans were included in this retrospective cohort study: children with craniosynostosis (n = 227), positional deformities (n = 206), and healthy children (n = 54). Three two-dimensional images were extracted from each photogrammetry scan. The datasets were divided into training, validation, and test sets. During the training, fine-tuned ResNet-152s were utilized. The performance was quantified using tenfold cross-validation. For the detection of craniosynostosis, sensitivity was at 0.94 with a specificity of 0.85. Regarding the differentiation of the five existing classes (trigonocephaly, scaphocephaly, positional plagiocephaly left, positional plagiocephaly right, and healthy), sensitivity ranged from 0.45 (positional plagiocephaly left) to 0.95 (scaphocephaly) and specificity ranged from 0.87 (positional plagiocephaly right) to 0.97 (scaphocephaly). We present a CNN-based approach to classify craniofacial deformities on two-dimensional images with promising results. A larger dataset would be required to identify rarer forms of craniosynostosis as well. The chosen 2D approach enables future applications for digital cameras or smartphones.
Exploring the Role of Biomarkers Associated with Alveolar Damage and Dysfunction in Idiopathic Pulmonary Fibrosis—A Systematic Review
Authors: Zamfir Alexandra-Simona , Zabara Mihai Lucian , Arcana Raluca Ioana , Cernomaz Tudor Andrei , Zabara-Antal Andreea , Marcu Marius Traian Dragoș , Trofor Antigona , Zamfir Carmen Lăcrămioara , Crișan-Dabija Radu
Published: November 2023

Background: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases (ILDs), marked by an ongoing, chronic fibrotic process within the lung tissue. IPF leads to an irreversible deterioration of lung function, ultimately resulting in an increased mortality rate. Therefore, the focus has shifted towards the biomarkers that might contribute to the early diagnosis, risk assessment, prognosis, and tracking of the treatment progress, including those associated with epithelial injury. Methods: We conducted this review through a systematic search of the relevant literature using established databases such as PubMed, Scopus, and Web of Science. Selected articles were assessed, with data extracted and synthesized to provide an overview of the current understanding of the existing biomarkers for IPF. Results: Signs of epithelial cell damage hold promise as relevant biomarkers for IPF, consequently offering valuable support in its clinical care. Their global and standardized utilization remains limited due to a lack of comprehensive information of their implications in IPF. Conclusions: Recognizing the aggressive nature of IPF among interstitial lung diseases and its profound impact on lung function and mortality, the exploration of biomarkers becomes pivotal for early diagnosis, risk assessment, prognostic evaluation, and therapy monitoring.
DLPformer: A Hybrid Mathematical Model for State of Charge Prediction in Electric Vehicles Using Machine Learning Approaches
Authors: Wang Yaoyidi , Chen Niansheng , Fan Guangyu , Yang Dingyu , Rao Lei , Cheng Songlin , Song Xiaoyong
Published: November 2023

Accurate mathematical modeling of state of charge (SOC) prediction is essential for battery management systems (BMSs) to improve battery utilization efficiency and ensure a good safety performance. The current SOC prediction framework only considers battery-related features but ignores vehicle information. Additionally, in light of the emergence of time-series Transformers (TSTs) that harness the power of multi-head attention, developing a SOC prediction model remains a significant challenge. Therefore, we introduce a new framework that integrates laboratory battery data with mathematical vehicle model features to improve the accuracy of the SOC and propose a prediction model named DLPformer, which can effectively capture variations in the SOC attributed to both trend and seasonal patterns. First, we apply Matlab/Simulink to simulate a mathematical model of electric vehicles and process the generated vehicle data with Spearman correlation analysis to identify the most relevant features, such as the mechanical losses of the electric motor, differential, and aerodynamic drag. Then, we employ a data fusion method to synchronize the heterogeneous datasets with different frequencies to capture the sudden changes in electric vehicles. Subsequently, the fused features are input into our prediction model, DLPformer, which incorporates a linear model for trend prediction and patch-input attention for seasonal component prediction. Finally, in order to effectively evaluate the extrapolation and adaptability of our model, we utilize different driving cycles and heterogeneous battery datasets for training and testing. The experimental results show that our prediction model significantly improves the accuracy and robustness of SOC prediction under the proposed framework, achieving MAE values of 0.18% and 0.10% across distinct driving cycles and battery types.
A Deep Joint Network for Monocular Depth Estimation Based on Pseudo-Depth Supervision
Authors: Tan Jiahai , Gao Ming , Duan Tao , Gao Xiaomei
Published: November 2023

Depth estimation from a single image is a significant task. Although deep learning methods hold great promise in this area, they still face a number of challenges, including the limited modeling of nonlocal dependencies, lack of effective loss function joint optimization models, and difficulty in accurately estimating object edges. In order to further increase the network’s prediction accuracy, a new structure and training method are proposed for single-image depth estimation in this research. A pseudo-depth network is first deployed for generating a single-image depth prior, and by constructing connecting paths between multi-scale local features using the proposed up-mapping and jumping modules, the network can integrate representations and recover fine details. A deep network is also designed to capture and convey global context by utilizing the Transformer Conv module and Unet Depth net to extract and refine global features. The two networks jointly provide meaningful coarse and fine features to predict high-quality depth images from single RGB images. In addition, multiple joint losses are utilized to enhance the training model. A series of experiments are carried out to confirm and demonstrate the efficacy of our method. The proposed method exceeds the advanced method DPT by 10% and 3.3% in terms of root mean square error (RMSE(log)) and 1.7% and 1.6% in terms of squared relative difference (SRD), respectively, according to experimental results on the NYU Depth V2 and KITTI depth estimation benchmarks.
Reconstruction Using a Scrotal Flap with Autologous Augmentation for Delayed Infection Caused by Penile Filler Injection: A Case Report
Authors: Son Hee-Jun , Pae Woo-Sik
Published: November 2023

Penile augmentation using filler injections is gaining popularity; however, complications such as foreign body reactions can arise, leading to issues like penile ulceration and necrosis, subsequently necessitating reconstruction. The existing method of the reconstruction of the penis is primarily aimed at filling the deficit. In this paper, we describe a case in which a scrotal flap and autologous augmentation were utilized to treat a soft tissue defect caused by a delayed infection following a penile filler injection. The patient, a 41-year-old male, had received an Aquafilling® (Biomedica, Prague, Czech Republic) filler injection seven years earlier and later developed a delayed infection. After debridement, the penile defect spanned the entire shaft, and the circumference of the flaccid penis was 7.5 cm. Using a bilateral scrotal flap technique, the lower margins of both flaps were rolled inward after de-epithelialization to achieve autologous augmentation. Over the three-month post-surgery follow-up, neither infections nor flap necrosis were observed. The penile circumference increased to 12 cm, and the patient reported high satisfaction with the outcome. This new surgical technique can be widely applied as treatment for a variety of penile defects.
High-Temperature Oxidation of Boiler Steels at 650 °C
Authors: Burja Jaka , Šetina Batič Barbara , Žužek Borut , Balaško Tilen
Published: November 2023

This study presents a comprehensive investigation of the formation, composition and behaviour of oxide layers during the high-temperature oxidation of four different steel alloys (16Mo3, 13Cr, T24 and P91) at a uniform temperature of 650 °C. The study is aimed at assessing the oxidation damage due to short-term overheating. The research combines CALPHAD (CALculation of PHAse Diagrams) calculations, thermogravimetric analysis (TGA) and advanced microscopy techniques, including scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD), to elucidate the complex mechanisms controlling oxidation kinetics and oxide layer development. CALPHAD calculations were used to determine the thermodynamically stable phases for each steel type at 650 °C and different oxygen activities. The results showed different phase compositions, highlighting the importance of the chromium content in steel for the formation of oxide layers. The different oxidation kinetics and oxide layer compositions are presented and associated with the increased risk of material degradation due to overheating. These results have significant implications for industrial applications, mainly the susceptibility to oxidation of low-alloyed steels like 16Mo3 and 13 Cr and contribute to a deeper understanding of oxidation processes in steels.
Influence of the Chemical Composition on the Phase Stability and Mechanical Properties of Biomedical Ti-Nb-Mo-Zr Alloys
Authors: Nunes Aline Raquel Vieira , Borborema Sinara , Araújo Leonardo Sales , Rodrigues Taissa Zangerolami Lopes , Malet Loïc , Dille Jean , de Almeida Luiz Henrique
Published: November 2023

A new generation of titanium alloys with non-toxic, non-allergenic elements and lower Young’s modulus (YM) have been developed, presenting modulus values close to that of bone. In titanium alloys, the value of the Young’s modulus is strongly dependent on the chemical composition. Young’s modulus also depends on the present phases and on the crystallographic texture related to the thermomechanical processing. A lower YM is normally attributed to the formation of the α″ phase into the β matrix, but there is no consensus for this assumption. In the present work, four alloys were designed and melted, based on the Ti-Nb-Mo-Zr system and heat-treated to favor the formation of the β phase. The alloys were produced by arc melting under argon atmosphere and heat-treated at 1000 °C for 24 h under high vacuum, being subsequently quenched in water to room temperature. Alloys were then characterized by optical microscopy (OM), X-ray diffraction (XRD) and transmission electron microscopy (TEM). Young’s modulus was determined by the impulse excitation technique and Vickers microhardness. The purpose of the study was to define an optimal chemical composition for the further production on a semi-industrial scale of a new Ti-Nb-Mo-Zr alloy for orthopedic implant manufacturing. The results showed that all of the four studied alloys are potential candidates for biomedical applications. Among them, the Ti-24Nb-4Mo-6Zr alloy has the lowest Young’s modulus and the highest microhardness. So, this alloy presents the highest HV/YM ratio, which is a key indicator in order to evaluate the mechanical performance of metallic biomaterials for orthopedic implants.
Systematical Investigation of Flicker Noise in 14 nm FinFET Devices towards Stochastic Computing Application
Authors: Dong Danian , Lai Jinru , Yang Yan , Gong Tiancheng , Zheng Xu , Sun Wenxuan , Yu Jie , Fan Shaoyang , Xu Xiaoxin
Published: November 2023

Stochastic computing (SC) is widely known for its high error tolerance and efficient computing ability of complex functions with remarkably simple logic gates. The noise of electronic devices is widely used to be the entropy source due to its randomness. Compared with thermal noise and random telegraph noise (RTN), flicker noise is favored by researchers because of its high noise density. Meanwhile, unlike using RRAM, PCRAM and other emerging memory devices as the entropy source, using logic devices does not require any additional process steps, which is significant for industrialization. In this work, we systematically and statistically studied the 1/f noise characteristics of 14 nm FinFET, and found that miniaturizing the channel area of the device or lowering the ambient temperature can effectively increase the 1/f noise density of the device. This is of great importance to improve the accuracy of the SC system and simplify the complexity of the stochastic number generator (SNG) circuit. At the same time, these rules of 1/f noise characteristics in FinFET devices can provide good guidance for our device selection in circuit design.
Risk Assessment for the Spread of Flavescence Dorée-Related Phytoplasmas from Alder to Grapevine by Alternative Insect Vectors in Germany
Authors: Jarausch Barbara , Markheiser Anna , Jarausch Wolfgang , Biancu Sandra , Kugler Sanela , Runne Miriam , Maixner Michael
Published: November 2023

“Flavescence dorée” (FD)-related phytoplasmas are widespread in alder in Germany and their transmission to grapevine represents a high risk for FD outbreaks when the primary vector, Scaphoideus titanus, becomes present in the future. Therefore, the potential role of the Deltocephalinae leafhopper species in transmitting FD-related phytoplasmas from alder to grapevine was studied in extensive transmission trials conducted between 2017 and 2020. The transmission capacity of autochthonous Allygus spp. and the invasive Orientus ishidae captured on infected alder trees was tested under controlled conditions using various test designs, including grouped insects and single-insect studies. The latter experiments were analyzed in terms of survival probability, transmission success and phytoplasma load in the insects, measured by quantitative PCR. A minimum inoculation titer (MIT) required for successful transmission to alder was defined for both Allygus spp. and O. ishidae. While Allygus spp. exhibited slightly better survival on Vitis vinifera compared to O. ishidae, the latter displayed higher phytoplasma loads and greater transmission success. Although all species were capable of infecting alder seedlings, O. ishidae was able to transmit 16SrV-phytoplasmas directly to single grapevines. Infective adults of O. ishidae were captured from the beginning of July until the end of August, while Allygus spp. were only considered infective towards the end of the season. Thus, O. ishidae likely poses a higher risk for FD transmission from alder to grapevine, albeit at a very low level, as only five out of 90 transmission trials to V. vinifera were successful.
A Convenient One-Pot Synthesis of a Sterically Demanding Aniline from Aryllithium Using Trimethylsilyl Azide, Conversion to β-Diketimines and Synthesis of a β-Diketiminate Magnesium Hydride Complex
Authors: Demidov Nikita , Grebogi Mateus , Bourne Connor , McKay Aidan P. , Cordes David B. , Stasch Andreas
Published: November 2023

This work reports the one-pot synthesis of sterically demanding aniline derivatives from aryllithium species utilising trimethylsilyl azide to introduce amine functionalities and conversions to new examples of a common N,N′-chelating ligand system. The reaction of TripLi (Trip = 2,4,6-iPr3-C6H2) with trimethylsilyl azide afforded the silyltriazene TripN2N(SiMe3)2 in situ, which readily reacts with methanol under dinitrogen elimination to the aniline TripNH2 in good yield. The reaction pathways and by-products of the system have been studied. The extension of this reaction to a much more sterically demanding terphenyl system suggested that TerLi (Ter = 2,6-Trip2-C6H3) slowly reacted with trimethylsilyl azide to form a silyl(terphenyl)triazenide lithium complex in situ, predominantly underwent nitrogen loss to TerN(SiMe3)Li in parallel, which afforded TerN(SiMe3)H after workup, and can be deprotected under acidic conditions to form the aniline TerNH2. TripNH2 was furthermore converted to the sterically demanding β-diketimines RTripnacnacH (=HC{RCN(Trip)}2H), with R = Me, Et and iPr, in one-pot procedures from the corresponding 1,3-diketones. The bulkiest proligand was employed to synthesise the magnesium hydride complex [{(iPrTripnacnac)MgH}2], which shows a distorted dimeric structure caused by the substituents of the sterically demanding ligand moieties.
Core–Shell Structure Trimetallic Sulfide@N-Doped Carbon Composites as Anodes for Enhanced Lithium-Ion Storage Performance
Authors: Li Xiuyan , Zhu Liangxing , Yang Chenyu , Wang Yinan , Gu Shaonan , Zhou Guowei
Published: November 2023

The high specific capacity of transition metal sulfides (TMSs) opens up a promising new development direction for lithium-ion batteries with high energy storage. However, the poor conductivity and serious volume expansion during charge and discharge hinder their further development. In this work, trimetallic sulfide Zn–Co–Fe–S@nitrogen-doped carbon (Zn–Co–Fe–S@N–C) polyhedron composite with a core–shell structure is synthesized through a simple self-template method using ZnCoFe–ZIF as precursor, followed by a dopamine surface polymerization process and sulfidation during high-temperature calcination. The obvious space between the internal core and the external shell of the Zn–Co–Fe–S@N–C composites can effectively alleviate the volume expansion and shorten the diffusion path of Li ions during charge and discharge cycles. The nitrogen-doped carbon shell not only significantly improves the electrical conductivity of the material, but also strengthens the structural stability of the material. The synergistic effect between polymetallic sulfides improves the electrochemical reactivity. When used as an anode in lithium-ion batteries (LIBs), the prepared Zn–Co–Fe–S@N–C composite exhibits a high specific capacity retention (966.6 mA h g−1 after 100 cycles at current rate of 100 mA g−1) and good cyclic stability (499.17 mA h g−1 after 120 cycles at current rate of 2000 mA g−1).
Effects of Harvest Time and Hydrodistillation Time on Yield, Composition, and Antioxidant Activity of Mint Essential Oil
Authors: Marques Samara de Paula Pinheiro Menezes , Pinheiro Rafaela Oliveira , Nascimento Rafael Alves do , Andrade Eloísa Helena de Aguiar , Faria Lênio José Guerreiro de
Published: November 2023

In this study, we assessed the effects of different harvest times (9 a.m., 1 p.m., and 5 p.m.) and hydrodistillation times (60, 90, and 120 min) on the yield, chemical composition, and antioxidant activity of the spearmint (Mentha spicata L.) essential oil (EO) sourced from the Amazon region. EO yield was ≥1.55% and was not significantly influenced (p ≥ 0.05) by the different harvest times and hydrodistillation times. Thirty-one different organic compounds were identified, of which menthol (91.56–95.68%), menthone (0.6–2.72%), and isomenthone (0.55–1.46%) were the major constituents. The highest menthol content in the EO was obtained from samples collected at 9 a.m., with a hydrodistillation time of 60–90 min, compared to other harvest and hydrodistillation times. This suggests that exposure to sun and light, which is greater at harvest times of 1 p.m. and 5 p.m., decreased the menthol content and altered the chemical composition of Mentha EO. Furthermore, the sample harvested at 9 a.m. and hydrodistilled for 60 min showed the highest antioxidant activity (61.67 equivalent mg of Trolox per g of EO), indicating that antioxidant activity is strongly affected by light exposure and the contact duration of the sample with boiling water during hydrodistillation.
Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated Chitosan Nanoparticles in MCF-7 Breast Cancer Cells
Authors: Herdiana Yedi , Wathoni Nasrul , Shamsuddin Shaharum , Muchtaridi Muchtaridi
Published: November 2023

α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer.
Molecular Hybridization of Alkaloids Using 1,2,3-Triazole-Based Click Chemistry
Authors: Buchanan Devan , Pham Ashley M. , Singh Sandeep K. , Panda Siva S.
Published: November 2023

Alkaloids found in multiple species, known as ‘driver species’, are more likely to be included in early-stage drug development due to their high biodiversity compared to rare alkaloids. Many synthetic approaches have been employed to hybridize the natural alkaloids in drug development. Click chemistry is a highly efficient and versatile reaction targeting specific areas, making it a valuable tool for creating complex natural products and diverse molecular structures. It has been used to create hybrid alkaloids that address their limitations and serve as potential drugs that mimic natural products. In this review, we highlight the recent advancements made in modifying alkaloids using click chemistry and their potential medicinal applications. We discuss the significance, current trends, and prospects of click chemistry in natural product-based medicine. Furthermore, we have employed computational methods to evaluate the ADMET properties and drug-like qualities of hybrid molecules.
Improving the Performance of Polydimethylsiloxane-Based Triboelectric Nanogenerators by Introducing CdS Particles into the Polydimethylsiloxane Layer
Authors: Mao Jianbin , Seo Soonmin
Published: November 2023

Energy harvesting and power generation technologies hold significant potential for meeting future energy demands and improving environmental sustainability. A triboelectric nanogenerator (TENG), which harnesses energy from the surrounding environment, has garnered significant attention as a promising and sustainable power source applicable in various fields. In this study, we present a technique to improve the triboelectric performance of a PDMS-based TENG by incorporating nanostructured cadmium sulfide (N-CdS). This study investigates the utilization of CdS nanomaterials in TENG production, where mechanical energy is converted into electrical energy. We conducted a comparative analysis of TENGs utilizing N-CdS/PDMS, commercial CdS/PDMS (C-CdS/PDMS), and pure PDMS substrates. The N-CdS/PDMS substrates demonstrated superior triboelectric performance compared to TENG devices based on pure PDMS and C-CdS/PDMS. The triboelectric open-circuit voltage (Voc) and short-circuit current (Isc) of the N-CdS/PDMS-based TENG device were approximately 236 V and 17.4 µA, respectively, when operated at a 2 Hz frequency. These values were approximately 3 times and 2.5 times higher, respectively, compared to the pure PDMS-based TENGs. They were further studied in detail to understand the effect of different parameters such as contact–separation frequency and contact force on the TENGs’ operation. The stability of the TENG devices was studied, and their potential to be integrated into self-powered smart textiles as power sources was demonstrated.
Mitochondrial Dysfunction and Nanocarrier-Based Treatments in Chronic Obstructive Pulmonary Disease (COPD)
Authors: Sato Kiyoshi , Kawakami Hiroyoshi
Published: November 2023

Mitochondrial dysfunction significantly contributes to the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). To treat mitochondrial dysfunction in COPD, novel drug delivery systems (DDS) are needed. In this review, we provide a brief overview of the current understanding of the factors in COPD and highlight the trends in novel nanocarriers/nanoparticles for targeting mitochondrial dysfunction. These drug-encapsulated nanoparticles are still in the early stages of clinical application but represent the most promising system for COPD therapy.
Cervical HPV Infections, Sexually Transmitted Bacterial Pathogens and Cytology Findings—A Molecular Epidemiology Study
Authors: Valasoulis George , Pouliakis Abraham , Michail Georgios , Magaliou Ioulia , Parthenis Christos , Margari Niki , Kottaridi Christine , Spathis Aris , Leventakou Danai , Ieronimaki Argyro-Ioanna , Androutsopoulos Georgios , Panagopoulos Periklis , Daponte Alexandros , Tsiodras Sotirios , Panayiotides Ioannis G.
Published: November 2023

Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years (p < 0.05)) was associated with negative STI testing. Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI (OR: 2.69, 95% CI 2.10–3.46, p < 0.05). Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation.
Pathogen-Mediated Alterations of Insect Chemical Communication: From Pheromones to Behavior
Authors: Moyano Andrea , Croce Anna Cleta , Scolari Francesca
Published: November 2023

Pathogens can influence the physiology and behavior of both animal and plant hosts in a manner that promotes their own transmission and dispersal. Recent research focusing on insects has revealed that these manipulations can extend to the production of pheromones, which are pivotal in chemical communication. This review provides an overview of the current state of research and available data concerning the impacts of bacterial, viral, fungal, and eukaryotic pathogens on chemical communication across different insect orders. While our understanding of the influence of pathogenic bacteria on host chemical profiles is still limited, viral infections have been shown to induce behavioral changes in the host, such as altered pheromone production, olfaction, and locomotion. Entomopathogenic fungi affect host chemical communication by manipulating cuticular hydrocarbons and pheromone production, while various eukaryotic parasites have been observed to influence insect behavior by affecting the production of pheromones and other chemical cues. The effects induced by these infections are explored in the context of the evolutionary advantages they confer to the pathogen. The molecular mechanisms governing the observed pathogen-mediated behavioral changes, as well as the dynamic and mutually influential relationships between the pathogen and its host, are still poorly understood. A deeper comprehension of these mechanisms will prove invaluable in identifying novel targets in the perspective of practical applications aimed at controlling detrimental insect species.
Synergistic In Vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils, and 18-(Phthalimid-2-yl)ferruginol against Arboviruses and Herpesvirus
Authors: Betancur-Galvis Liliana , Jimenez-Jarava Orlando José , Rivas Fatima , Mendoza-Hernández William E. , González-Cardenete Miguel A.
Published: November 2023

Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction in the antiviral effective concentration of drugs already approved by the FDA, such as ivermectin (IVM), ribavirin (RIBA), and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV), and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecules with broad-spectrum antiviral activity, the ferruginol analog 18-(phthalimid-2-yl)ferruginol (phthFGL), which presented an IC99 of 25.6 μM for the three types of virus. In general, the combination of IVM, phthFGL, and oregano EO showed the greatest synergism potential against CHIKV, ZIKV, and HHV-2. For instance, this combination achieved reductions in the IC99 value of each component up to ~8-, ~27-, and ~12-fold for CHIKV, respectively. The ternary combination of RIBA, phthFGL, and oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, and oregano EO, which indicates that IVM could contribute more to the differentiation of cell targets (for example via the inhibition of the host heterodimeric importin IMP α/β1 complex) than ribavirin. Statistical analysis showed significant differences among the combination groups tested, especially in the HHV-2 and CHIKV models, with p = 0.0098. Additionally, phthFGL showed a good pharmacokinetic profile that should encourage future optimization studies.
Entecavir: A Review and Considerations for Its Application in Oncology
Authors: Lourenço Tânia , Vale Nuno
Published: November 2023

Entecavir (ETV) is a drug used as a first-line treatment for chronic hepatitis B (CHB) virus infection because it is a guanosine nucleoside analogue with activity against the hepatitis B virus polymerase. The ETV dosage can range from 0.5 mg to 1 mg once a day and the most common side effects include headache, insomnia, fatigue, dizziness, somnolence, vomiting, diarrhea, nausea, dyspepsia, and increased liver enzyme levels. In addition to its conventional use, ETV acts as an inhibitor of lysine-specific demethylase 5B (KDM5B), an enzyme that is overexpressed in breast, lung, skin, liver, and prostate tumors and is involved in the hormonal response, stem cell regeneration, genomic stability, cell proliferation, and differentiation. The KDM5B enzyme acts as a transcriptional repressor in tumor suppressor genes, silencing them, and its overexpression leads to drug resistance in certain tumor types. Furthermore, the literature suggests that KDM5B activates the PI3K/AKT signaling pathway, while reducing KDM5B expression decreases AKT signaling, resulting in decreased tumor cell proliferation. In silico studies have demonstrated that ETV can inhibit tumor cell proliferation and induce apoptosis by reducing KDM5B expression. ETV also appears to inhibit PARP-1, has a high genetic barrier, reducing the chance of resistance development, and can also prevent the reactivation of the hepatitis B virus in cancer patients, which have proven to be significant advantages regarding its use as a repurposed drug in oncology. Therefore, ETV holds promise beyond its original therapeutic indication.
Neuroprotective Effects of Davallia mariesii Roots and Its Active Constituents on Scopolamine-Induced Memory Impairment in In Vivo and In Vitro Studies
Authors: Lee Chung Hyeon , Ko Min Sung , Kim Ye Seul , Ham Ju Eon , Choi Jee Yeon , Hwang Kwang Woo , Park So-Young
Published: November 2023

Beta-amyloid (Aβ) proteins, major contributors to Alzheimer’s disease (AD), are overproduced and accumulate as oligomers and fibrils. These protein accumulations lead to significant changes in neuronal structure and function, ultimately resulting in the neuronal cell death observed in AD. Consequently, substances that can inhibit Aβ production and/or accumulation are of great interest for AD prevention and treatment. In the course of an ongoing search for natural products, the roots of Davallia mariesii T. Moore ex Baker were selected as a promising candidate with anti-amyloidogenic effects. The ethanol extract of D. mariesii roots, along with its active constituents, not only markedly reduced Aβ production by decreasing β-secretase expression in APP–CHO cells (Chinese hamster ovary cells which stably express amyloid precursor proteins), but also exhibited the ability to diminish Aβ aggregation while enhancing the disaggregation of Aβ aggregates, as determined through the Thioflavin T (Th T) assay. Furthermore, in an in vivo study, the extract of D. mariesii roots showed potential (a tendency) for mitigating scopolamine-induced memory impairment, as evidenced by results from the Morris water maze test and the passive avoidance test, which correlated with reduced Aβ deposition. Additionally, the levels of acetylcholine were significantly elevated, and acetylcholinesterase levels significantly decreased in the brains of mice (whole brains). The treatment with the extract of D. mariesii roots also led to upregulated brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p-CREB) in the hippocampal region. These findings suggest that the extract of D. mariesii roots, along with its active constituents, may offer neuroprotective effects against AD. Consequently, there is potential for the development of the extract of D. mariesii roots and its active constituents as effective therapeutic or preventative agents for AD.
Isolation and Identification of 12-Deoxyphorbol Esters from Euphorbia resinifera Berg Latex: Targeted and Biased Non-Targeted Identification of 12-Deoxyphorbol Esters by UHPLC-HRMSE
Authors: Ezzanad Abdellah , De los Reyes Carolina , Macías-Sánchez Antonio J. , Hernández-Galán Rosario
Published: November 2023

Diterpenes from the Euphorbia genus are known for their ability to regulate the protein kinase C (PKC) family, which mediates their ability to promote the proliferation of neural precursor cells (NPCs) or neuroblast differentiation into neurons. In this work, we describe the isolation from E. resinifera Berg latex of fifteen 12-deoxyphorbol esters (1–15). A triester of 12-deoxy-16-hydroxyphorbol (4) and a 12-deoxyphorbol 13,20-diester (13) are described here for the first time. Additionally, detailed structural elucidation is provided for compounds 3, 5, 6, 14 and 15. The absolute configuration for compounds 3, 4, 6, 13, 14 and 15 was established by the comparison of their theoretical and experimental electronic circular dichroism (ECD) spectra. Access to the above-described collection of 12-deoxyphorbol derivatives, with several substitution patterns and attached acyl moieties, allowed for the study of their fragmentation patterns in the collision-induced dissociation of multiple ions, without precursor ion isolation mass spectra experiments (HRMSE), which, in turn, revealed a correlation between specific substitution patterns and the fragmentation pathways in their HRMSE spectra. In turn, this allowed for a targeted UHPLC-HRMSE analysis and a biased non-targeted UHPLC-HRMSE analysis of 12-deoxyphorbols in E. resinifera latex which yielded the detection and identification of four additional 12-deoxyphorbols not previously isolated in the initial column fractionation work. One of them, identified as 12-deoxy-16-hydroxyphorbol 20-acetate 13-phenylacetate 16-propionate (20), has not been described before.
Green Energy Storage: Chitosan-Avocado Starch Hydrogels for a Novel Generation of Zinc Battery Electrolytes
Authors: Cruz-Balaz María I. , Bósquez-Cáceres María Fernanda , Delgado Anabel D. , Arjona Noé , Morera Córdova Vivian , Álvarez-Contreras Lorena , Tafur Juan P.
Published: November 2023

Meeting the ever-increasing global energy demands through sustainable and environmentally friendly means is a paramount challenge. In response to this imperative, this study is dedicated to the development of biopolymer electrolytes, which hold promise for improving the efficiency, safety, and biodegradability of energy systems. The present study aims to evaluate hydrogels synthesized from chitosan biopolymer and starch from avocado seed residues in different ratios, and dried using freeze-thawing and freeze-drying techniques. Epichlorohydrin was used as a chemical crosslinker to create a suitable degree of swelling using an ionic solution. Physical freezing crosslinking strategies such as freezing–thawing and freezing–drying were performed to generate a denser porous structure in the polymer matrix. Subsequently, synthesized electrolytes were immersed in 12 M KOH solution to improve their electrochemical properties. The effect of the different ratios of starch in the hydrogels on the structural properties of the materials was evaluated using characterization techniques such as FTIR and XRD, which allowed to confirm the crosslinking between chitosan and starch. The electrochemical performance of the hydrogels is assessed using electrochemical impedance spectroscopy. A maximum conductivity value of 0.61 S·cm−1 was achieved at room temperature. The designed materials were tested in prototype zinc–air batteries; their specific capacity value was 1618 mA h·g−1, and their obtained power density was 90 mW·cm−2. These substantial findings unequivocally underscore the potential of the synthesized hydrogels as highly promising electrolytes for the application in zinc–air battery systems.
Genetic Association of Diagnostic Traits of Metabolic Syndrome with Lysosomal Pathways: Insights from Target Gene Enrichment Analysis
Authors: An Yeeun , Seo Yunji , Lee Chaeyoung
Published: November 2023

Genome-wide association studies (GWAS) identified many association signals for metabolic syndrome (MetS). However, the understanding of its pathophysiology may be limited because of the complexity of the intertwined genetic factors that underlie diagnostic condition traits. We conducted an enrichment analysis of spatial expression genes (eGenes) associated with GWAS signals for MetS and its diagnostic condition traits. Consequently, eGenes associated with MetS were significantly enriched in 14 biological pathways (PBH < 0.05, where PBH is the p-value adjusted for Benjamini–Hochberg multiple testing). Moreover, 38 biological pathways were additionally identified in the enrichment analysis of the individual diagnostic traits (PBH < 0.05). In particular, the lysosomal pathway was revealed for waist-to-hip ratio, glucose measurement, and high-density lipoprotein cholesterol (PBH < 0.05), but not for MetS (PBH > 0.05). It was inferred that lysosomal pathway-based control of cellular lipid metabolism and insulin secretion/resistance could result in eGene enrichment for these diagnostic traits. In conclusion, this target gene enrichment analysis of diagnostic traits of MetS uncovered a lysosomal pathway that may dilute its effects on the MetS. We propose that lysosomal dysfunction should be a priority for research on the underlying pathogenic mechanisms of MetS and its diagnostic traits. Experimental studies are needed to elucidate causal relationships of ribosomal pathways with metabolic syndrome and its diagnostic traits.