bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Sex and Genetic Variation in Relevant Pharmacogenes on the Pharmacokinetics and Safety of Valsartan, Olmesartan and Hydrochlorothiazide
Authors: Soria-Chacartegui Paula , Zubiaur Pablo , Ochoa Dolores , Navares-Gómez Marcos , Abbes Houwaida , Villapalos-García Gonzalo , de Miguel Alejandro , González-Iglesias Eva , Rodríguez-Lopez Andrea , Mejía-Abril Gina , Martín-Vilchez Samuel , Luquero-Bueno Sergio , Román Manuel , Abad-Santos Francisco
Published: October 2023

Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters’ genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (Cmax) and time to reach it (tmax), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the ABCB1 rs1045642 T/T genotype were associated with a higher valsartan tmax compared to those with T/G and G/G genotypes (p < 0.001, β = 0.821, R2 = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, p = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC∞/DW) was observed in SLC22A1 rs34059508 G/A volunteers compared to G/G volunteers (p = 0.050, β = 1047.35, R2 = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, p = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics.
Mitochondrial and Proteasome Dysfunction Occurs in the Hearts of Mice Treated with Triazine Herbicide Prometryn
Authors: Sule Rasheed O. , Phinney Brett S. , Salemi Michelle R. , Gomes Aldrin V.
Published: October 2023

Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. Significant traces of prometryn are documented in the environment, mainly in waters, soil, and plants used for human and domestic consumption. Previous studies have shown that triazine herbicides have carcinogenic potential in humans. However, there is limited information about the effects of prometryn on the cardiac system in the literature, or the mechanisms and signaling pathways underlying any potential cytotoxic effects are not known. It is important to understand the possible effects of exogenous compounds such as prometryn on the heart. To determine the mechanisms and signaling pathways affected by prometryn (185 mg/kg every 48 h for seven days), we performed proteomic profiling of male mice heart with quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) using ten-plex tandem mass tag (TMT) labeling. The data suggest that several major pathways, including energy metabolism, protein degradation, fatty acid metabolism, calcium signaling, and antioxidant defense system were altered in the hearts of prometryn-treated mice. Proteasome and immunoproteasome activity assays and expression levels showed proteasome dysfunction in the hearts of prometryn-treated mice. The results suggest that prometryn induced changes in mitochondrial function and various signaling pathways within the heart, particularly affecting stress-related responses.
EGF-Enhanced GnRH-II Regulation in Decidual Stromal Cell Motility through Twist and N-Cadherin Signaling
Authors: Wu Hsien-Ming , Chen Liang-Hsuan , Huang Hong-Yuan , Wang Hsin-Shih , Tsai Chia-Lung
Published: October 2023

Crucial roles in embryo implantation and placentation in humans include the invasion of the maternal decidua by extravillous trophoblasts and the motile behavior of decidual endometrial stromal cells. The effects of the epidermal growth factor (EGF) and GnRH-II in the endometrium take part in early pregnancy. In the present study, we demonstrated the coaction of EGF- and GnRH-II-promoted motility of human decidual endometrial stromal cells, indicating the possible roles of EGF and GnRH-II in embryo implantation and early pregnancy. After obtaining informed consent, we obtained human decidual endometrial stromal cells from decidual tissues from normal pregnancies at 6 to 12 weeks of gestation in healthy women undergoing suction dilation and curettage. Cell motility was evaluated with invasion and migration assays. The mechanisms of EGF and GnRH-II were performed using real-time PCR and immunoblot analysis. The results showed that human decidual tissue and stromal cells expressed the EGF and GnRH-I receptors. GnRH-II-mediated cell motility was enhanced by EGF and was suppressed by the knockdown of the endogenous GnRH-I receptor and EGF receptor with siRNA, revealing that GnRH-II promoted the cell motility of human decidual endometrial stromal cells through the GnRH-I receptor and the activation of Twist and N-cadherin signaling. This new concept regarding the coaction of EGF- and GnRH-promoted cell motility suggests that EGF and GnRH-II potentially affect embryo implantation and the decidual programming of human pregnancy.
Cytotoxic Impact of Fluorinated Ligands in Equatorial Position of Trans-Configured Diam(m)inetetracarboxylatoplatinum(IV) Complexes
Authors: Lerchbammer-Kreith Yvonne , Hejl Michaela , Wenisch Dominik , Jakupec Michael A. , Galanski Mathea S. , Keppler Bernhard K.
Published: October 2023

A series of thirty novel tetracarboxylatoplatinum(IV) complexes in trans-configuration featuring combinations of mixed ammine, methylamine, dimethylamine, and cyclopentylamine ligands as well as acetato/propanoato and trifluoropropanoato ligands was synthesised. The platinum(IV) complexes were characterised by one- and two-dimensional multinuclear NMR spectroscopy (1H, 13C, 15N, 19F, 195Pt), ESI-MS, elemental analysis, and X-ray diffraction. Additional parameters such as reduction behaviour and lipophilicity were measured via NMR spectroscopy and RP-HPLC, revealing slow reduction and a broad spectrum of log kw values in line with the respective ligand combination. In order to determine structure–activity relationships, cytotoxic activity was evaluated via the MTT assay in three human cancer cell lines (CH1/PA-1, ovarian teratocarcinoma, SW480, colon adenocarcinoma, A549, non-small-cell lung carcinoma). The induction of apoptosis and necrosis was determined in SW480 cells via the flow-cytometric annexin V/PI assay. In general, a tendency of higher lipophilicity leading to higher cytotoxicity was noticed. In contrast, lipophilicity alone plays a subordinate role for the induction of apoptosis, which strongly depends on the combination of am(m)ine and trifluoropropanoato ligands.
Sepsis Management in the Cardiac Intensive Care Unit
Authors: Zhang Yichi , McCurdy Michael T. , Ludmir Jonathan
Published: October 2023

Septic shock management in the cardiac intensive care unit (CICU) is challenging due to the complex interaction of pathophysiology between vasodilatory and cardiogenic shock, complicating how to optimally deploy fluid resuscitation, vasopressors, and mechanical circulatory support devices. Because mixed shock portends high mortality and morbidity, familiarity with quality, contemporary clinical evidence surrounding available therapeutic tools is needed to address the resultant wide range of complications that can arise. This review integrates pathophysiology principles and clinical recommendations to provide an organized, topic-based review of the nuanced intricacies of managing sepsis in the CICU.
OX40 (CD134) Expression on T Regulatory Cells Is Related to Serious Hypertensive Disorders in Pregnancy
Authors: Kwiatek Maciej , Kojak Agnieszka , Kwaśniewska Anna
Published: October 2023

Hypertension is one of the leading causes of morbidity and mortality among women related to pregnancy, childbirth and the postpartum period. The pathogenesis of gestational hypertension is complex and still not fully understood. The aim of this study was to assess the population of circulating CD4+CD25+FoxP3+ cells and its differentiation in terms of OX40 expression in two forms of hypertension: isolated hypertension developing after the 20th week of pregnancy and pre-eclampsia. The study included a group of 60 patients with hypertension and 48 healthy controls. The analysis of the percentage of Tregs was performed by flow cytometry. There was no difference in the percentage of peripheral lymphocytes between the groups. In the group of women with preeclampsia compared to the group with gestational hypertension, significantly higher percentages of CD4+CD25+FoxP3+ cells (p = 0.03) and percentages of CD4+CD25+FoxP3+ cells expressing the OX40 antigen (p = 0.001) were observed. OX40 expression on Tregs seems to be related to more serious type of hypertensive disorders in pregnant women.
Forward-Looking Sonar-Based Stream Function Algorithm for Obstacle Avoidance in Autonomous Underwater Vehicles
Authors: Kim Moon Hwan , Yoo Teasuk , Park Seok Joon , Oh Kyungwon
Published: October 2023

Autonomous Underwater Vehicles (AUVs) have emerged as pivotal tools for intricate underwater missions, spanning seafloor exploration to meticulous inspection of subsea infrastructures such as pipelines and cables. Although terrestrial obstacle avoidance paradigms exhibit proficiency, their efficacy diminishes in aquatic environments due to the nuanced challenges and distinct dynamics inherent to marine realms and AUV maneuvering. This paper presents an advanced obstacle avoidance algorithm for AUVs based on a stream function framework. Central to this approach is the utilization of a stream function, further nuanced by a radial histogram that serves as the defining cost function. This work also encapsulates constraints related to the maximum allowed path curvature, ensuring enhanced path optimization. Comprehensive simulation results validate the robustness and adaptability of the introduced strategy, evincing its capacity to outline both practicable and optimal evasion trajectories across diverse operational contexts.
Research on Johnson–Cook Constitutive Model of γ-TiAl Alloy with Improved Parameters
Authors: Shi Limin , Wang Tong , Wang Liang , Liu Erliang
Published: October 2023

Due to its excellent physical properties, γ-TiAl alloy has been widely used in thin-walled components of aerospace engines. However, issues such as low thermal conductivity, poor machinability, and high cutting temperatures often result in difficulties in ensuring the geometric accuracy and surface integrity of the parts. This paper focuses on the study of the thermal deformation behavior of γ-TiAl alloy within a range of higher temperatures and strain rates. Firstly, by conducting quasi-static tests and Hopkinson bar tests on γ-TiAl alloy, the true stress–strain curves of γ-TiAl alloy are obtained within a temperature range of 20~500 °C and a strain rate range of 3000~11,000/s. Based on the Johnson–Cook model, the true stress–strain curves are fitted and analyzed with consideration of the coupling effect of strain rate, temperature, and strain. The strain rate hardening coefficient C and thermal softening exponent m are polynomialized, improving the Johnson–Cook constitutive model of γ-TiAl alloy. The improved model shows significant improvements in the correlation coefficient and absolute errors between the predicted values and experimental values, providing a better reflection of the thermal deformation behavior of γ-TiAl alloy within a range of higher temperatures and strain rates.
Study of the Mechanical Properties and Microstructure of Spiral Tubes and Actuators for Controlled Extension Fabricated with Beryllium Bronze Strips
Authors: Lu Ruilong , Han Jingtao , Li Zhanhua , Zhang Congfa , Liu Jiawei , Liu Cheng , Lang Zhenqian , Ma Xiaoyan
Published: October 2023

QBe2.0 strips were used to fabricate spiral tubes and actuators for controlled extension (STACERs) through the winding and stabilization method, which is a novel technique for obtaining STACERs. The raw strips and the STACERs were investigated using tensile tests and SEM for the mechanical properties and fractography observation, employing specialized test equipment for service performance, and via XRD, EBSD, and TEM were used to test the residual stress and microstructure evolution. The tensile strength/elongation for raw strips was 485.8 MPa/60%, while for STACERs, tensile strength increased by 834.67 MPa to 646 MPa, and the elongation rate decreased by 12% to 19.3%. The fractography showed that the fracture mode was ductile. The service performance tests indicated that STACERs obtained under 320 °C had a higher driving force, good pointing accuracy, and high bending stiffness, while the residual stress of raw strips was τxy = −6 MPa; for STACERs obtained between 290 °C and 350 °C, τxy decreased from −5 MPa to −74 MPa, then increased from −74 MPa to 21 MPa, and the optimum fabricating parameter was 320 °C + 2 h. The EBSD results showed that LABs and HABs for raw strips and STACERs at 320 °C + 2 h accounted for 3–97% and 24.5–75.5%, the grain sizes were 7.07 μm and 3.67 μm, and the twin fraction decreased from 57.3% to 31.8%, respectively. The KAM and Schmid factor maps indicated that the STACER was prone to recovering and recrystallizing. Coupled with the EBSD results, the TEM results indicated that the strengthening mechanism for raw strips is twinning strengthening, while that for STACER is grain-refining strengthening with a precipitation of the γ″ phase. It is a meaningful novelty that the relationship between the macro properties and microstructure has been elucidated.
Research on Processability and Transmission Performance of Low Temperature Co-Fired Ceramic Ball Grid Array Packaging Based on Electroless Plating Surface Modification for Microwave Transceiver Circuits
Authors: Wang Song , Hou Tianyu , Huo Rui , Chen Zhengtian , Zeng Qinghua , He Ying , Zhao Yan , Liu Xiao
Published: October 2023

A microwave transmitter/receiver using the low-temperature co-fired ceramic substrate and ball grid array packaging demonstrates superior properties, including high integration, miniaturization, and high electromagnetic shielding. However, it holds limitations of inadequate hermeticity (that is, gas or moist impermeability), high cost, and low reproducibility. In this work, we aim to overcome these difficulties by introducing a new packing technique. The packaging utilizes an electroless plated Ni/Pd/Au surface, resulting in a significant enhancement of the packaging hermeticity by orders of magnitude, approaching the level of <5 × 10−9 Pa·m3/s. Both Sn63Pb37 and Au80Sn20 solder alloys demonstrate exceptional solderability, attributed to Pd atoms diffusing to the Au layer during soldering at 310 °C. A reliability test of the packaging shows that the shear strength of the solder balls drops after thermal shocks but negligibly affects the hermeticity of the packaging. Furthermore, a meticulously designed internal vertical interconnect structure and I/O interconnections were engineered in the ball grid array packaging, showcasing excellent transmission characteristics within the 10–40 GHz frequency range while ensuring effective isolation between ports.
Local Electrochemical Corrosion of 6061 Aluminum Alloy with Nano-SiO2/MAO Composite Coating
Authors: Zhao Jie , Zhang Hongwei , Yang Xiaoyu , Gu Yanhong , Liu Yida
Published: October 2023

To improve the corrosion resistance of 6061 Al in electric vehicle battery packs, a composite coating of nano-SiO2/Micro-Arc oxidation (MAO) ceramic structure was prepared on its surface. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization curves (PDP) were used to evaluate the corrosion resistance of the specimens after 7 days immersion in a 3.5% NaCl solution. The corrosion resistance of the prefabricated coatings was measured via local electrochemical impedance spectroscopy (LEIS). Confocal microscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD) were used to characterize the microstructure and phase composition of the specimens. An energy dispersive spectrometer (EDS) was used to detect the elemental composition of the surface of the specimen. The results showed that the specimen with nano-SiO2/MAO composite coating had the least amount of micropores and superior corrosion resistance. The global electrochemical impedance of nano-SiO2/MAO composite coating was 1.1 times higher than that of the MAO coating and 8.4 times higher than that of the 6061 Al. When the coating was defective, the local electrochemical impedance of the nano-SiO2/MAO composite coating was still two times higher than that of the MAO coating. In the presence of scratches, the nano-SiO2/MAO composite coating still showed high corrosion resistance. The collapse corrosion mechanism of the nano-SiO2/MAO composite coating was proposed.
Microwave-Prepared Quantum Dots and Their Potential Applications as Adsorbents and Chemosensors
Authors: Tohamy Hebat-Allah S. , El-Sakhawy Mohamed , Hassan El Barbary , Kamel Samir
Published: October 2023

A combination of different eco-friendly materials prepared promising fluorescent quantum dots (QDs) through the one-step process using the microwave heating of urea with cellulose, chitosan, and biochar. Characterizations of the prepared QDs, including the investigation of their structure by infrared spectroscopy, Raman analysis, X-ray diffraction, thermal gravimetric analysis, morphology, and optical properties, were performed. The results showed that QDs possess a small size, high UV absorption, and excitation wavelength-dependent fluorescence. The prepared QDs were also tested for metal ions removal from aqueous solutions. The adsorption at different contact times was investigated to optimize the adsorption efficiency of the prepared QDs. All QDs were found to be an ideal sorbent for Cr(II), Cu(II), Mn(II), and Pb(II). From the data, Cr(II) was more highly adsorbed than other metal ions. The results of the kinetic investigation showed that the pseudo-second-order kinetic model fit the adsorption process effectively. In addition, the fluorescence spectra of QDs were changed after the adsorption of metal ions; hence, the prepared QDs could be utilized in environmental sectors such as wastewater pollution detection, adsorption, and chemical sensing applications.
Statistical Study of the Process Parameters for Achieving Continuous Consolidation of a Thermoplastic Composite
Authors: Campos Daniel , Maimí Pere , Martín Alberto
Published: October 2023

Manufacturing components using thermoplastic composite materials necessitates a judicious balance among fabrication parameters, cost considerations and the ultimate quality of the elements produced. Continuous manufacturing technologies, exemplified by methods such as continuous compressing molding and glide forming, seek to revolutionize production through their continuous processing approach. This study aimed to investigate the effects different process parameters have on the final quality of the manufactured parts when a continuous manufacturing technology, such as glide forming, is applied to thermoplastic composite materials. An experimental rig was designed, and 19 samples were prepared using a unidirectional-carbon-fiber-reinforced LM-PAEK (low-melting polyaryletherketone) composite. The process parameters studied were temperature, pressure and forming speed. The quality of the final parts was evaluated based on their thickness and consolidation levels. The findings underscore the feasibility of leveraging continuous manufacturing technologies for producing components using thermoplastic composite materials, but the process parameters must be carefully controlled to ensure the quality of the final part. The models obtained could be used as a post-processing tool to predict thickness and consolidation levels when simulating the manufacture of a component on macroscale levels. Further research is needed to optimize the process parameters and study their effects on other thermoplastic composite materials.
Modification of the Human Amniotic Membrane Using Different Cross-Linking Agents as a Promising Tool for Regenerative Medicine
Authors: Skopinska-Wisniewska Joanna , Michalak Marlena , Tworkiewicz Jakub , Tyloch Dominik , Tuszynska Marta , Bajek Anna
Published: October 2023

Human amniotic membranes (hAMs) obtained during cesarean sections have proven to be clinically useful as an interesting biomaterial in a wide range of tissue engineering applications such as ocular surface reconstruction, burn treatments, chronic wounds, or bedsore ulcers. It presents antimicrobial properties, promotes epithelization, reduces inflammation and angiogenesis, contains growth factors, and constitutes the reservoir of stem cells. However, variability in hAM stiffness and its fast degradation offers an explanation for the poor clinical applications and reproducibility. In addition, the preparatory method of hAM for clinical use can affect its mechanical properties, and these differences can influence its application. As a directly applied biomaterial, the hAM should be available in a ready-to-use manner in clinical settings. In the present study, we performed an analysis to improve the mechanical properties of hAM by the addition of various reagents used as protein cross-linkers: EDC/NHS, PEG-dialdehyde, PEG-NHS, dialdehyde starch, and squaric acid. The effect of hAM modification using different cross-linking agents was determined via infrared spectroscopy, thermal analyses, mechanical properties analyses, enzymatic degradation, and cytotoxicity tests. The use of PEG-dialdehyde, PEG-NHS, dialdehyde starch, and squaric acid increases the mechanical strength and elongation at the breaking point of hAM, while the addition of EDC/NHS results in material stiffening and shrinkage. Also, the thermal stability and degradation resistance were evaluated, demonstrating higher values after cross-linking. Overall, these results suggest that modification of human amniotic membrane by various reagents used as protein cross-linkers may make it easier to use hAM in clinical applications, and the presented study is a step forward in the standardization of the hAM preparation method.
The Effect of Chemical and Thermal Treatment for Desizing on the Properties and Chemical Functional Groups of Carbon Fiber
Authors: Kim Kyungeun , Kim Minsu , Kim Gyungha , Kim Daeup
Published: October 2023

In this paper, in order to upcycle carbon fibers (CF), the changes in their mechanical and chemical properties in accordance with time and temperature were investigated, in addition to the oxygen functional group mechanism. When acetone as a chemical desizing agent was used, treatment with acetone for 0.5 h at 60 °C was the optimal condition for the complete removal of the sizing agent, and there was no deterioration in tensile strength. At 25 °C, the carbonyl group (C=O) and hydroxyl group (C-O) declined in comparison to commercial CF, but a novel lactone group (O=C-O) was created. At 60 °C, the oxygen present in the sizing agent was removed and C=O, C-O, and O=C-O decreased. On the contrary, in the case of thermal desizing in an inert gas nitrogen atmosphere, by increasing the temperature, functional groups combining carbon and oxygen were reduced, because nitrogen and oxygen atoms combined with C=O and C-O on the CF surface were eliminated in the form of CO, NO, CO2, NO2, and O2. When desizing via chemical and thermal methods, the amount of functional groups combining carbon and oxygen on the CF surface decreased. Desizing was performed as a pretreatment for surface treatment, so the methods and conditions were different, and related research is insufficient. In this study, we attempted to derive the optimal conditions for desizing treatment by identifying the surface characteristics and mechanisms according to chemical and thermal desizing treatment methods.
Event-Triggered Second-Order Sliding Mode Controller Design and Implementation
Authors: Sarjaš Andrej , Gleich Dušan
Published: October 2023

The paper presents an event-triggered higher-order sliding mode controller design. The event-triggering technique is the alternative approach to real-time controller execution, unlike the classic time-triggering technique, which is not time-dependable and is governed by the triggering policy. The technique is suitable for system resource relaxation in case of computation burden or network usage mitigation. The paper describes the stability analysis of the super-twisted sliding mode controller based on input-to-state stability notation. The stability analysis introduces a triggering policy related directly to the ultimate boundness of the system states and preselected sliding variables. The controller time execution with the selected triggering condition prevents the exhibition of the Zeno phenomena, where the minimal inter-event time of the controller has a positive non-zero lower bound. The minimal value of the inter-event time is related directly to the controller parameters and triggering bound, the selection of which is given with the derived stability conditions regarding the designer’s objective. Preventing the fast nonlinear controller execution, especially close to the sliding manifold, also alleviates the chattering phenomena effectively, which is a primal drawback, and limits the usage of the controller on various systems. The method’s efficiency is verified with the hardware-in-the-loop system, where the dynamic and robustness of the triggering approach are compared to the standard time-triggered execution technique.
Structure-Aware Low-Rank Adaptation for Parameter-Efficient Fine-Tuning
Authors: Hu Yahao , Xie Yifei , Wang Tianfeng , Chen Man , Pan Zhisong
Published: October 2023

With the growing scale of pre-trained language models (PLMs), full parameter fine-tuning becomes prohibitively expensive and practically infeasible. Therefore, parameter-efficient adaptation techniques for PLMs have been proposed to learn through incremental updates of pre-trained weights, such as in low-rank adaptation (LoRA). However, LoRA relies on heuristics to select the modules and layers to which it is applied, and assigns them the same rank. As a consequence, any fine-tuning that ignores the structural information between modules and layers is suboptimal. In this work, we propose structure-aware low-rank adaptation (SaLoRA), which adaptively learns the intrinsic rank of each incremental matrix by removing rank-0 components during training. We conduct comprehensive experiments using pre-trained models of different scales in both task-oriented (GLUE) and task-agnostic (Yelp and GYAFC) settings. The experimental results show that SaLoRA effectively captures the structure-aware intrinsic rank. Moreover, our method consistently outperforms LoRA without significantly compromising training efficiency.
A Contemporary Approach of Integral Khan-Type Multivalued Contractions with Generalized Dynamic Process and an Application
Authors: Mudhesh Mustafa , Hussain Aftab , Arshad Muhammad , Alsulami Hamed
Published: October 2023

The aim of this article is to investigate the relationship between integral-type contractions and the generalized dynamic process. The fixed-point results for multivalued mappings that satisfy both the integral Khan-type contraction and the integral θ-contraction are established in a complete metric space. Furthermore, some corollaries are derived based on our main contribution. To demonstrate the novelty of our findings, several examples are provided. Finally, we look into whether nonlinear fractional differential equations have solutions utilizing the obtained results.
Spectral Analysis of One Class of Positive-Definite Operators and Their Application in Fractional Calculus
Authors: Matseevich Tatiana , Aleroev Temirkhan
Published: October 2023

This paper is devoted to the spectral analysis of one class of integral operators, associated with the boundary-value problems for differential equations of fractional order. In particular, we show the positive definiteness of studying operators, which makes it possible to select areas in the complex plane where there are no eigenvalues for these operators.
Organic Synthesis of New Secosteroids from Fucosterol, Its Intestinal Absorption by Caco-2 Cells, and Simulation of the Biological Activities of Vitamin D
Authors: Komba Shiro , Hase Megumi , Kotake-Nara Eiichi
Published: October 2023

We previously examined the cellular uptake of six types of vitamin D in human intestinal Caco-2 cells. Since vitamins D5–D7 were commercially unavailable, we synthesized these compounds organically before studying them. This process led us to understand that new secosteroids could be generated as vitamin D candidates, depending on the sterol used as the starting material. We obtained two new secosteroids—compounds 3 and 4—from fucosterol in the current study. We investigated the intestinal absorption of these compounds using Caco-2 cells cultured in Transwells and compared the results with vitamin D3, a representative secosteroid. The intestinal absorption of compound 4 was comparable to that of vitamin D3. Compound 3 showed similar uptake levels but transported about half as much as vitamin D3. These compounds demonstrated intestinal absorption at the cellular level. Vitamin D is known for its diverse biological activities manifest after intestinal absorption. Using PASS online simulation, we estimated the biological activity of compound 3’s activated form. In several items indicated by PASS, compound 3 exhibited stronger biological activity than vitamins D2–D7 and was also predicted to have unique biological activities.
Lupus Nephritis in Children: Novel Perspectives
Authors: Pennesi Marco , Benvenuto Simone
Published: October 2023

Childhood-onset systemic lupus erythematosus is an inflammatory and autoimmune condition characterized by heterogeneous multisystem involvement and a chronic course with unpredictable flares. Kidney involvement, commonly called lupus nephritis, mainly presents with immune complex-mediated glomerulonephritis and is more frequent and severe in adults. Despite a considerable improvement in long-term renal prognosis, children and adolescents with lupus nephritis still experience significant morbidity and mortality. Moreover, current literature often lacks pediatric-specific data, leading clinicians to rely exclusively on adult therapeutic approaches. This review aims to describe pediatric lupus nephritis and provide an overview of the novel perspectives on the pathogenetic mechanisms, histopathological classification, therapeutic approach, novel biomarkers, and follow-up targets in children and adolescents with lupus nephritis.
A Randomized Controlled Trial of Vertebral Body Decompression Procedure Versus Conservative Treatment for Painful Vertebral Compression Fracture
Authors: Lee Sanghoon , Zheng Haolin , Park Sang-Min , Kim Ho-Joong , Yeom Jin S.
Published: October 2023

Background: Traditional treatment modalities for vertebral compression fractures (VCFs) include bed rest, pain medications, muscle relaxants, back braces, and physical therapy. In cases where conservative treatment proves ineffective, a new procedure called core decompression of the vertebral body is explored. Core decompression of the vertebral body has the potential to lower and stabilize the intraosseous pressure, resulting in enhanced blood circulation, which contributes to pain reduction. In this trial, we evaluated the efficacy of core decompression of the vertebral body in patients with painful VCFs compared with conventional conservative treatment. Methods: This prospective randomized controlled trial was conducted at a tertiary education hospital between June 2017 and May 2020. The participants were randomly assigned in a 1:1 ratio to one of two treatment groups: the core decompression group and the conservative treatment group. The primary outcome measure was the visual analog scale (VAS) pain score of the back 3 months after the procedure. Secondary outcome measures included the Oswestry Disability Index (ODI) for lumbar disabilities, the European Quality of Life-5 Dimensions (EQ-5D) score for quality of life, and radiographic outcomes such as changes in compression rate. Results: All patients underwent the assigned intervention (48 core decompression and 50 conservative treatments). At both 1 month and 3 months, there were no significant differences between the core decompression group and conservative treatment group in VAS pain score (adjusted treatment effect: −0.1 and 2.0; 95% confidence interval [CI]: −7.5 to 7.3 and −5.6 to 9.6; p = 0.970 and p = 0.601, respectively). In addition, there were no significant inter-group differences in ODI and EQ-5D scores throughout the follow-up period (p = 0.917 and 0.704, respectively). Conclusion: Core decompression of the vertebral body did not demonstrate any significant improvement in pain and disability compared to conventional conservative treatment.
Optimization of Laser Powder Bed Fusion Process for Forming Porous Ta Scaffold
Authors: Gao Lin , Wang Yikai , Qin Xiao , Lv Naixin , Tong Zhiqiang , Sun Changning , Li Dichen
Published: October 2023

To improve the performance of porous tantalum (Ta) manufactured by laser powder bed fusion (L-PBF) and meet its application requirements in medicine, the authors of this paper studied the influence of L-PBF process parameters on the strut surface morphology and mechanical performance. It was found that the powder layer thickness had a significant influence on the microstructure and mechanical properties based on statistical analysis. We proposed optimal process parameters of laser power of 150 W, scanning speed of 270 mm/s, thickness of 0.05 mm, and scanning spacing of 0.07 mm. After parameter optimization, we successfully obtained Ta samples with an elastic modulus of 1.352 ± 0.007 GPa and yield strength of 53.217 ± 0.114 MPa. The results show that the elastic modulus and yield strength of porous Ta samples with a porosity of 80% under the optimal process parameters are significantly superior to previous studies. The porous Ta scaffolds with higher mechanical properties fabricated with the optimized process parameters of L-PBF have significant value for applications in medicine.
The Nature of the Chemical Bonds of High-Valent Transition–Metal Oxo (M=O) and Peroxo (MOO) Compounds: A Historical Perspective of the Metal Oxyl–Radical Character by the Classical to Quantum Computations
Authors: Yamaguchi Kizashi , Isobe Hiroshi , Shoji Mitsuo , Kawakami Takashi , Miyagawa Koichi
Published: October 2023

This review article describes a historical perspective of elucidation of the nature of the chemical bonds of the high-valent transition metal oxo (M=O) and peroxo (M-O-O) compounds in chemistry and biology. The basic concepts and theoretical backgrounds of the broken-symmetry (BS) method are revisited to explain orbital symmetry conservation and orbital symmetry breaking for the theoretical characterization of four different mechanisms of chemical reactions. Beyond BS methods using the natural orbitals (UNO) of the BS solutions, such as UNO CI (CC), are also revisited for the elucidation of the scope and applicability of the BS methods. Several chemical indices have been derived as the conceptual bridges between the BS and beyond BS methods. The BS molecular orbital models have been employed to explain the metal oxyl-radical character of the M=O and M-O-O bonds, which respond to their radical reactivity. The isolobal and isospin analogy between carbonyl oxide R2C-O-O and metal peroxide LFe-O-O has been applied to understand and explain the chameleonic chemical reactivity of these compounds. The isolobal and isospin analogy among Fe=O, O=O, and O have also provided the triplet atomic oxygen (3O) model for non-heme Fe(IV)=O species with strong radical reactivity. The chameleonic reactivity of the compounds I (Cpd I) and II (Cpd II) is also explained by this analogy. The early proposals obtained by these theoretical models have been examined based on recent computational results by hybrid DFT (UHDFT), DLPNO CCSD(T0), CASPT2, and UNO CI (CC) methods and quantum computing (QC).
Advancements in Preprocessing and Analysis of Nitrite and Nitrate since 2010 in Biological Samples: A Review
Authors: Liu Guojie , Guo Honghui , Zhao Wanlin , Yan Hongmu , Zhang Enze , Gao Lina
Published: October 2023

As a substance present in organisms, nitrite is a metabolite of nitric oxide and can also be ingested. Nitrate is the metabolite of nitrite. Therefore, it is necessary to measure it quickly, easily and accurately to evaluate the health status of humans. Although there have been several reviews on analytical methods for non-biological samples, there have been no reviews focused on both sample preparation and analytical methods for biological samples. First, rapid and accurate nitrite measurement has significant effects on human health. Second, the detection of nitrite in biological samples is problematic due to its very low concentration and matrix interferences. Therefore, the pretreatment plus measuring methods for nitrite and nitrate obtained from biological samples since 2010 are summarized in the present review, and their prospects for the future are proposed. The treatment methods include liquid–liquid microextraction, various derivatization reactions, liquid–liquid extraction, protein precipitation, solid phase extraction, and cloud point extraction. Analytical methods include spectroscopic methods, paper-based analytical devices, ion chromatography, liquid chromatography, gas chromatography–mass spectrometry, electrochemical methods, liquid chromatography–mass spectrometry and capillary electrophoresis. Derivatization reagents with rapid quantitative reactions and advanced extraction methods with high enrichment efficiency are also included. Nitrate and nitrate should be determined at the same time by the same analytical method. In addition, much exploration has been performed on formulating fast testing through microfluidic technology. In this review, the newest developments in nitrite and nitrate processing are a focus in addition to novel techniques employed in such analyses.
In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic
Authors: Alkahtani Hamad M. , Almehizia Abdulrahman A. , Al-Omar Mohamed A. , Obaidullah Ahmad J. , Zen Amer A. , Hassan Ashraf S. , Aboulthana Wael M.
Published: October 2023

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base–pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer’s (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer’s, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer’s (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.
TMT-Based Proteomics Reveal the Mechanism of Action of Amygdalin against Rheumatoid Arthritis in a Rat Model through Regulation of Complement and Coagulation Cascades
Authors: Zhou Lan , Chai Jun-Hong , Zhang Yi , Jing Xiao-Jie , Kong Xiang-Wen , Liang Jun , Xia Yong-Gang
Published: October 2023

The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund’s adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.
Paving the Way towards Sustainability of Polyurethanes: Synthesis and Properties of Terpene-Based Diisocyanate
Authors: Delavarde Aliénor , Lemouzy Sebastien , Lebrun Aurélien , Pinaud Julien , Caillol Sylvain
Published: October 2023

Due to growing concerns about environmental issues and the decline of petroleum-based resources, the synthesis of new biobased compounds for the polymer industry has become a prominent and timely topic. P-menthane-1,8-diamine (PMDA) is a readily available compound synthesized from turpentine, a cheap mixture of natural compounds isolated from pine trees. PMDA has been extensively used for its biological activities, but it can also serve as a source of valuable monomers for the polymer industry. In this work, commercial PMDA (ca. 85% pure) was purified by salinization, crystallization, and alkali treatment and then converted into p-menthane-1,8-diisocyanate (PMDI) through a phosgene-free synthesis at room temperature. A thorough analytical study using NMR techniques (1H, 13C, 13C-1H HSQC, 13C-1H HMBC, and 1H-1H NOESY) enables the characterization of the cis-trans isomeric mixtures of both PMDA and PMDI. These structural studies allowed for a better understanding of the spatial configuration of both isomers. Then, the reactivity of PMDI with a primary alcohol (benzyl alcohol) was studied in the presence of nine different catalysts exhibiting different activation modes. Finally, the use of PMDI in the synthesis of polyurethanes was explored to demonstrate that PMDI can be employed as a new biobased alternative to petrochemical-based isocyanates such as isophorone diisocyanate (IPDI).
Engineering the Electronic Structure towards Visible Lights Photocatalysis of CaTiO3 Perovskites by Cation (La/Ce)-Anion (N/S) Co-Doping: A First-Principles Study
Authors: Zhang Qiankai , Wang Yang , Jia Yonggang , Yan Wenchao , Li Qinghao , Zhou Jun , Wu Kai
Published: October 2023

Cation-anion co-doping has proven to be an effective method of improving the photocatalytic performances of CaTiO3 perovskites. In this regard, (La/Ce-N/S) co-doped CaTiO3 models were investigated for the first time using first-principles calculations based on a supercell of 2 × 2 × 2 with La/Ce concentrations of 0.125, 0.25, and 0.375. The energy band structure, density of states, charge differential density, electron-hole effective masses, optical properties, and the water redox potential were calculated for various models. According to our results, (La-S)-doped CaTiO3 with a doping ratio of 0.25 (LCOS1-0.25) has superior photocatalytic hydrolysis properties due to the synergistic performances of its narrow band gap, fast carrier mobility, and superb ability to absorb visible light. Apart from the reduction of the band gap, the introduction of intermediate energy levels by La and Ce within the band gap also facilitates the transition of excited electrons from valence to the conduction band. Our calculations and findings provide theoretical insights and solid predictions for discovering CaTiO3 perovskites with excellent photocatalysis performances.
A Workflow Combining Machine Learning with Molecular Simulations Uncovers Potential Dual-Target Inhibitors against BTK and JAK3
Authors: Liu Lu , Na Risong , Yang Lianjuan , Liu Jixiang , Tan Yingjia , Zhao Xi , Huang Xuri , Chen Xuecheng
Published: October 2023

The drug development process suffers from low success rates and requires expensive and time-consuming procedures. The traditional one drug–one target paradigm is often inadequate to treat multifactorial diseases. Multitarget drugs may potentially address problems such as adverse reactions to drugs. With the aim to discover a multitarget potential inhibitor for B-cell lymphoma treatment, herein, we developed a general pipeline combining machine learning, the interpretable model SHapley Additive exPlanation (SHAP), and molecular dynamics simulations to predict active compounds and fragments. Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3) are popular synergistic targets for B-cell lymphoma. We used this pipeline approach to identify prospective potential dual inhibitors from a natural product database and screened three candidate inhibitors with acceptable drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Ultimately, the compound CNP0266747 with specialized binding conformations that exhibited potential binding free energy against BTK and JAK3 was selected as the optimum choice. Furthermore, we also identified key residues and fingerprint features of this dual-target inhibitor of BTK and JAK3.