bluuebunny/crossref_metadata_2025 huggingface dataset:
A 3D Predictive Method for Deep-Seated Gold Deposits in the Northwest Jiaodong Peninsula and Predicted Results of Main Metallogenic Belts
Authors: Song Mingchun , Li Shiyong , Zheng Jifei , Wang Bin , Fan Jiameng , Yang Zhenliang , Wen Guijun , Liu Hongbo , He Chunyan , Zhang Liangliang , Liu Xiangdong
Published: July 2022

With the rapid depletion of mineral resources, deep prospecting is becoming a frontier field in international geological exploration. The prediction of deep mineral resources is the premise and foundation of deep prospecting. However, conventional metallogenic predictive methods, which are mainly based on surface geophysical, geochemical, and remote sensing data and geological information, are no longer suitable for deep metallogenic prediction due to the large burial depth of deep-seated deposits. Consequently, 3D metallogenic prediction becomes a critical method for delineating deep prospecting target areas. As a world-class giant gold metallogenic province, the Jiaodong Peninsula is at the forefront in China in terms of deep prospecting achievements and exploration depth. Therefore, it has unique conditions for 3D metallogenic prediction and plays an important exemplary role in promoting the development of global deep prospecting. This study briefly introduced the method, bases, and results of the 3D metallogenic prediction in the northwest Jiaodong Peninsula and then established 3D geological models of gold concentration areas in the northwest Jiaodong Peninsula using drilling combined with geophysics. Since gold deposits in the northwest Jiaodong Peninsula are often controlled by faulting in the 3D space, this study proposed a method for predicting deep prospecting target areas based on a stepped metallogenic model and a method for predicting the deep resource potential of gold deposits based on the shallow resources of ore-controlling faults. Multiple characteristic variables were extracted from the 3D geological models of the gold concentration areas, including the buffer zone and dip angle of faults, the changing rate of fault dip angle, and the equidistant distribution of orebodies. Using these characteristic variables, five deep prospecting target areas in the Jiaojia and Sanshandao faults were predicted. Moreover, based on the proven gold resources at an elevation of −2000 m and above, the total gold resources of the Sanshandao, Jiaojia, and Zhaoping ore-controlling faults at an elevation of −5000–−2000 m were predicted to be approximately 3377–6490 t of Au. Therefore, it is believed that the total gold resources in the Jiaodong Peninsula are expected to exceed 10,000 t. These new predicted results suggest that the northwest Jiaodong Peninsula has huge potential for the resources of deep gold deposits, laying the foundation for further deep prospecting.
The Impact of Soil pH on Heavy Metals Uptake and Photosynthesis Efficiency in Melissa officinalis, Taraxacum officinalis, Ocimum basilicum
Authors: Adamczyk-Szabela Dorota , Wolf Wojciech M.
Published: July 2022

Herbs used in medicine should be grown under controlled and standardized conditions. Agricultural practices often induce changes to soil pH, which may affect migration of heavy metals in the environment, their accumulation in plant tissues and the concentration of medicinal ingredients. The aim of this work was to assess the influence of various soil pH on the biological parameters and uptake of manganese, copper and zinc by basil, dandelion and lemon balm. The soil analysis covered pH, organic matter content, bioavailable and total forms of investigated metals in soil. In plants cultivated in soil at pH covering the range 4.7–8.5 the concentrations of Mn, Cu and Zn were analyzed. Their mobility and availability were assessed by bioaccumulation factors, translocation factors and transfer coefficients. The seed germination and subsequent herbs growth were strongly dependent on soil pH for all investigated plant species. Photosynthetic efficiency at different pHs was positively correlated with uptake of Cu and Mn while Zn behaved in a more random way.
Na2S-Mediated One-Pot Selective Deoxygenation of α-Hydroxyl Carbonyl Compounds including Natural Products
Authors: Xu Xiaobo , Yan Leyu , Zhang Zhi-Kai , Lu Bingqing , Guo Zhuangwen , Chen Mengyue , Cao Zhong-Yan
Published: July 2022

A practical method for the deoxygenation of α-hydroxyl carbonyl compounds under mild reaction conditions is reported here. The use of cheap and easy-to-handle Na2S·9H2O as the reductant in the presence of PPh3 and N-chlorosuccinimide (NCS) enables the selective dehydroxylation of α-hydroxyl carbonyl compounds, including ketones, esters, amides, imides and nitrile groups. The synthetic utility is demonstrated by the late-stage deoxygenation of bioactive molecule and complex natural products.
Cancer-Associated Mutations of the Adenosine A2A Receptor Have Diverse Influences on Ligand Binding and Receptor Functions
Authors: Feng Chenlin , Wang Xuesong , Jespers Willem , Liu Rongfang , Zamarbide Losada Sofía Denise , Gorostiola González Marina , van Westen Gerard J. P. , Danen Erik H. J. , Heitman Laura H.
Published: July 2022

The adenosine A2A receptor (A2AAR) is a class A G-protein-coupled receptor (GPCR). It is an immune checkpoint in the tumor micro-environment and has become an emerging target for cancer treatment. In this study, we aimed to explore the effects of cancer-patient-derived A2AAR mutations on ligand binding and receptor functions. The wild-type A2AAR and 15 mutants identified by Genomic Data Commons (GDC) in human cancers were expressed in HEK293T cells. Firstly, we found that the binding affinity for agonist NECA was decreased in six mutants but increased for the V275A mutant. Mutations A165V and A265V decreased the binding affinity for antagonist ZM241385. Secondly, we found that the potency of NECA (EC50) in an impedance-based cell-morphology assay was mostly correlated with the binding affinity for the different mutants. Moreover, S132L and H278N were found to shift the A2AAR towards the inactive state. Importantly, we found that ZM241385 could not inhibit the activation of V275A and P285L stimulated by NECA. Taken together, the cancer-associated mutations of A2AAR modulated ligand binding and receptor functions. This study provides fundamental insights into the structure–activity relationship of the A2AAR and provides insights for A2AAR-related personalized treatment in cancer.
Head-Space SPME for the Analysis of Organophosphorus Insecticides by Novel Silica IL-Based Fibers in Real Samples
Authors: Delińska Karolina , Yavir Kateryna , Kloskowski Adam
Published: July 2022

This work demonstrates the suitability of a newly developed ionic liquid (IL)-based silica SPME fiber for the determination of seven organophosphorus insecticides in cucumber and grapefruit samples by headspace solid-phase microextraction (HS-SPME) with a gas chromatography–flame ionization detector (FID). The sol-gel method released four different sorbent coatings, which were obtained based on a silica matrix containing ILs immobilized inside its pores. In order to obtain ionogel fibers, the following ionic liquids were utilized: 1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide; Butyltriethyl ammonium bis(trifluoromethylsulfonyl)imide; 1-(2-Methoxyethyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, and 1-Benzyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. The developed fibers were applied for the extraction of seven different insecticides from liquid samples. The most important extraction parameters of HS-SPME coupled with the GC-FID method were optimized with a central composite design. The new SPME fiber demonstrated higher selectivity for extracting the analyzed insecticides compared with commercially available fibers. The limit of detection was in the range of 0.01–0.93 μg L−1, the coefficients of determination were >0.9830, and 4.8–10.1% repeatability of the method was found. Finally, the obtained ionogel fibers were utilized to determine insecticides in fresh cucumber and grapefruit juices.
Novel Co5 and Ni4 Metal Complexes and Ferromagnets by the Combination of 2-Pyridyl Oximes with Polycarboxylic Ligands
Authors: Dimakopoulou Foteini , Efthymiou Costantinos G. , O’Malley Ciaran , Kourtellaris Andreas , Moushi Eleni , Tasiopooulos Anastasios , Perlepes Spyros P. , McArdle Patrick , Costa-Villén Ernesto , Mayans Julia , Papatriantafyllopoulou Constantina
Published: July 2022

The use of 2-pyridyl oximes in metal complexes chemistry has been extensively investigated in the last few decades as a fruitful source of species with interesting magnetic properties. In this work, the initial combination of pyridine-2-amidoxime (pyaoxH2) and 2-methyl pyridyl ketoxime (mpkoH) with isonicotinic acid (HINA) and 3,5-pyrazole dicarboxylic acid (H3pdc) has provided access to three new compounds, [Ni4(INA)2(pyaox)2(pyaoxH)2(DMF)2] (1), [Co5(mpko)6(mpkoH)2(OMe)2(H2O)](ClO4)6 (2), and [Co5(OH)(Hpdc)5(H2pdc)] (3). 1 displays a square-planar metal topology, being the first example that bears simultaneously HINA and pyaoxH2 in their neutral or ionic form. The neighbouring Ni4 units in 1 are held together through strong intermolecular hydrogen bonding interactions, forming a three-dimensional supramolecular framework. 2 and 3 are mixed-valent Co4IIICoII and Co2IIICoII3 compounds with a bowtie and trigonal bipyramidal metal topology, accordingly. Direct current and alternate current magnetic susceptibility studies revealed that the exchange interactions between the NiII ions in 1 are ferromagnetic (J = 1.79(4) cm−1), while 2 exhibits weak AC signals in the presence of a magnetic field. The syntheses, crystal structures, and magnetic properties of 1–3 are discussed in detail.
Supported Poly(Ionic Liquid)-Heteropolyacid Based Materials for Heterogeneous Catalytic Fructose Dehydration in Aqueous Medium
Authors: García-López Elisa I. , Campisciano Vincenzo , Giacalone Francesco , Liotta Leonarda Francesca , Marcì Giuseppe
Published: July 2022

Two sets of four different supported catalyst materials were prepared. One set was obtained by polymerization of a bis-vinylimidazolium salt, which formed a poly(ionic liquid) coating on SiO2, TiO2, boron nitride BN, and carbon nitride C3N4. The other set was, instead, obtained by immobilizing Keggin heteropolyacid H3PW12O40 onto poly-imidazolium functionalized materials. All the catalysts, including the bare supports, were subjected to physical and chemical characterization by XRD, SEM, Specific Surface Area and pore size measurements, TGA, FTIR, and acidity-basicity measurements. The catalytic activity of the materials was tested versus the fructose dehydration in water solution at two different sugar initial concentrations (0.3 and 1 M). Tests lasted 3 h with an amount of catalyst of 2 g∙L−1. The presence of the poly-imidazolium on the surface of the supports increased the catalytic conversion of fructose to 5-hydroxymethylfurfural (the most abundant compound obtained) and was further improved by the contemporary presence of the heteropolyacid, at least for the highest initial fructose concentration. In the latter conditions, the highest yield of 5-hydroxymethylfurfural (>40%) was also obtained.
Quantitative Raman Analysis of Carotenoid Protein Complexes in Aqueous Solution
Authors: Udensi Joy , Loskutova Ekaterina , Loughman James , Byrne Hugh J.
Published: July 2022

Carotenoids are naturally abundant, fat-soluble pigmented compounds with dietary, antioxidant and vision protection advantages. The dietary carotenoids, Beta Carotene, Lutein, and Zeaxanthin, complexed with in bovine serum albumin (BSA) in aqueous solution, were explored using Raman spectroscopy to differentiate and quantify their spectral signatures. UV visible absorption spectroscopy was employed to confirm the linearity of responses over the concentration range employed (0.05–1 mg/mL) and, of the 4 Raman source wavelengths (785 nm, 660 nm, 532 nm, 473 nm), 532 nm was chosen to provide the optimal response. After preprocessing to remove water and BSA contributions, and correct for self-absorption, a partial least squares model with R2 of 0.9995, resulted in an accuracy of the Root Mean Squared Error of Prediction for Beta Carotene of 0.0032 mg/mL and Limit of Detection 0.0106 mg/mL. Principal Components Analysis clearly differentiated solutions of the three carotenoids, based primarily on small shifts of the main peak at ~1520 cm−1. Least squares fitting analysis of the spectra of admixtures of the carotenoid:protein complexes showed reasonable correlation between norminal% and fitted%, yielding 100% contribution when fitted with individual carotenoid complexes and variable contributions with multiple ratios of admixtures. The results indicate the technique can potentially be used to quantify the carotenoid content of human serum and to identify their differential contributions for application in clinical analysis.
Use of a Hydrophobic Azo Dye for the Centrifuge-Less Cloud Point Extraction–Spectrophotometric Determination of Cobalt
Authors: Gavazov Kiril Blazhev , Racheva Petya V. , Milcheva Nikolina P. , Divarova Vidka V. , Kiradzhiyska Denitsa Dimitrova , Genç Fatma , Saravanska Antoaneta D.
Published: July 2022

The hydrophobic azo dye 6-hexyl-4-(2-thiazolylazo)resorcinol (HTAR, H2L) was studied as part of a system for the centrifuge-less cloud point extraction (CL-CPE) and spectrophotometric determination of traces of cobalt. The extracted 1:2 (Co:HTAR) complex, [CoIII(HL−)(L2−)]0, shows an absorption maximum at 553 nm and contains HTAR in two different acid–base forms. Optimum conditions for its formation and CL-CPE were found as follows: 1 × 10−5 mol L−1 of HTAR, 1.64% of Triton X-114, pH of 7.8, incubation time of 20 min at ca. 50 °C, and cooling time of 30 min at ca. −20 °C. The linear range, limit of detection, and apparent molar absorptivity coefficient were 5.4–189 ng mL−1, 1.64 ng mL−1, and 2.63 × 105 L mol−1 cm−1, respectively. The developed procedure does not use any organic solvents and can be described as simple, cheap, sensitive, convenient, and environmentally friendly. It was successfully applied to the analysis of artificial mixtures and real samples, such as steel, dental alloy, rainwater, ampoules of vitamin B12, and saline solution for intravenous infusion.
A Comparison Study on Polysaccharides Extracted from Atractylodes chinensis (DC.) Koidz. Using Different Methods: Structural Characterization and Anti-SGC-7901 Effect of Combination with Apatinib
Authors: Zhou Pingfan , Xiao Wanwan , Wang Xiaoshuang , Wu Yayun , Zhao Ruizhi , Wang Yan
Published: July 2022

For hundreds of years, Atractylodes chinensis (DC.) Koidz. (AK) has been widely used as a treatment for spleen and stomach diseases in China. The AK polysaccharides (AKPs) have been thought to be the important bioactive components. In this stud, the impacts of different extraction methods were analyzed. The differences between AKPs extracted by hot water extraction (HWE), AKPs extracted by ultrasonic extraction (UAE), and AKPs extracted by enzyme extraction (EAE) were compared in terms of yield, total carbohydrate content, molecular weight distribution, monosaccharide composition, and synergistic activity of the AKPs with apatinib were determined. The results indicated that the yield of the polysaccharide obtained from HWE was higher than that of UAE and EAE. However, activity assays indicated that UAE-AKPs and HWE-AKPs enhanced apoptosis of human gastric cancer cells (SGC-7901) treated with apatinib and UAE-AKPs showed the strongest synergistic activities. This is also in agreement with the fact that UAE-AKPs have a smaller molecular weight, β-configuration, and higher galactose content. These findings suggested that UAE is an efficient and environmentally friendly method for producing new polysaccharides from Atractylodes chinensis (DC.) Koidz. for the development of natural synergist and for the treatment of gastric cancer.
Preparation and Characterization of Methyl Jasmonate Microcapsules and Their Preserving Effects on Postharvest Potato Tuber
Authors: Han Xiaozhen , Shao Shuai , Han Xiaocui , Zhang Yurong
Published: July 2022

Potato tubers tend to sprout during long-term storage, resulting in quality deterioration and shortened shelf life. Restrictions on the use of chlorpropham, the major potato sprout suppressant, have led to a need to seek alternative methods. In this study, the effects of methyl jasmonate (MeJA) solutions and MeJA microcapsules on sprouting and other key quality attributes of the potato tuber were investigated. The results showed that the MeJA solution was most effective at 300 μmol L−1 according to TOPSIS analysis. To prepare MeJA microcapsules, the optimal formulation was with 0.04% emulsifier, 2.5% sodium alginate, 0.5% chitosan and 3% CaCl2. Compared to 300 μmol L−1 MeJA solution, MeJA microcapsules consumed a lower dose of MeJA but demonstrated a better retaining effect on the overall quality attributes of potato tubers. MeJA microcapsules are promising agents for the preservation of postharvest potato tubers.
Effects of Acute Yohimbine Hydrochloride Ingestion on Bench Press Performance in Resistance-Trained Males
Authors: Williams Tyler D. , Boag Lauren E. , Helton Clifford L. , Middleton M. Luke , Rogers Rebecca R. , Sternenberg Lillie H. , Ballmann Christopher G.
Published: July 2022

Yohimbine hydrochloride (YHM) is an alpha-2-adrenergic receptor antagonist that possesses sympathomimetic properties, but few studies have investigated YHM in the context of exercise. The purpose of this study was to examine the effects of acute YHM ingestion on bench press exercise power, velocity, and strength-endurance levels. In a double-blinded crossover design, resistance-trained males (n = 16) participated in two separate bench press trials, each with a different single-dose treatment: placebo (PL; gluten-free corn starch) or yohimbine hydrochloride (YHM; 2.5 mg). In each trial, the participants consumed their respective treatment 20 min prior to exercise. Following a warm-up, the participants completed 1 set × 2 explosive repetitions while a linear position transducer monitored the barbell velocity. The participants then completed 3 sets × repetitions to failure (RTF) at 75% of 1-repetition maximum (1-RM) separated by 2 min of rest. The motivation to exercise and subjective measures of energy or fatigue were measured post-exercise. The total RTF, mean velocity, mean power, motivation, and subjective energy or fatigue values were compared and analyzed. The mean power (p = 0.472; d = 0.16) and mean velocity (p = 0.297; d = 0.25) values were unchanged by treatment. However, the RTF (p = 0.002; d = 0.82) value was higher with YHM treatment. The motivation to exercise (p = 0.011; d = 0.64) and energy levels (p < 0.001; d = 1.27) were significantly higher with YHM ingestion versus PL. The subjective fatigue was significantly lower with YHM ingestion (p < 0.001; d = 1.65). In conclusion, the current findings show that YHM consumption enhanced muscular strength-endurance while improving feelings of motivation, energy, and fatigue. YHM ingestion may, therefore, be useful for athletes or competitors seeking to improve their performance or combat subjective fatigue.
In Search of Preferential Macrocyclic Hosts for Sulfur Mustard Sensing and Recognition: A Computational Investigation through the New Composite Method r2SCAN-3c of the Key Factors Influencing the Host-Guest Interactions
Authors: Messiad Fatine Ali , Ammouchi Nesrine , Belhocine Youghourta , Alhussain Hanan , Ghoniem Monira Galal , Said Ridha Ben , Ali Fatima Adam Mohamed , Rahali Seyfeddine
Published: July 2022

Sulfur mustard (SM) is a harmful warfare agent that poses a serious threat to human health and the environment. Thus, the design of porous materials capable of sensing and/or capturing SM is of utmost importance. In this paper, the interactions of SM and its derivatives with ethylpillar[5]arene (EtP[5]) and the interactions between SM and a variety of host macrocycles were investigated through molecular docking calculations and non-covalent interaction (NCI) analysis. The electronic quantum parameters were computed to assess the chemical sensing properties of the studied hosts toward SM. It was found that dispersion interactions contributed significantly to the overall complexation energy, leading to the stabilization of the investigated systems. DFT energy computations showed that SM was more efficiently complexed with DCMP[5] than the other hosts studied here. Furthermore, the studied macrocyclic containers could be used as host-based chemical sensors or receptors for SM. These findings could motivate experimenters to design efficient sensing and capturing materials for the detection of SM and its derivatives.
CO2 Activation and Hydrogenation on Cu-ZnO/Al2O3 Nanorod Catalysts: An In Situ FTIR Study
Authors: Wang Letian , Etim Ubong Jerome , Zhang Chenchen , Amirav Lilac , Zhong Ziyi
Published: July 2022

CuZnO/Al2O3 is the industrial catalyst used for methanol synthesis from syngas (CO + H2) and is also promising for the hydrogenation of CO2 to methanol. In this work, we synthesized Al2O3 nanorods (n-Al2O3) and impregnated them with the CuZnO component. The catalysts were evaluated for the hydrogenation of CO2 to methanol in a fixed-bed reactor. The support and the catalysts were characterized, including via in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The study of the CO2 adsorption, activation, and hydrogenation using in situ DRIFT spectroscopy revealed the different roles of the catalyst components. CO2 mainly adsorbed on the n-Al2O3 support, forming carbonate species. Cu was found to facilitate H2 dissociation and further reacted with the adsorbed carbonates on the n-Al2O3 support, transforming them to formate or additional intermediates. Like the n-Al2O3 support, the ZnO component contributed to improving the CO2 adsorption, facilitating the formation of more carbonate species on the catalyst surface and enhancing the efficiency of the CO2 activation and hydrogenation into methanol. The synergistic interaction between Cu and ZnO was found to be essential to increase the space–time yield (STY) of methanol but not to improve the selectivity. The 3% CuZnO/n-Al2O3 displayed improved catalytic performance compared to 3% Cu/n-Al2O3, reaching a CO2 conversion rate of 19.8% and methanol STY rate of 1.31 mmolgcat−1h−1 at 300 °C. This study provides fundamental and new insights into the distinctive roles of the different components of commercial methanol synthesis catalysts.
An Introduction of a Modular Framework for Securing 5G Networks and Beyond
Authors: Edris Ed Kamya Kiyemba , Aiash Mahdi , Loo Jonathan
Published: July 2022

Fifth Generation Mobile Network (5G) is a heterogeneous network in nature, made up of multiple systems and supported by different technologies. It will be supported by network services such as device-to-device (D2D) communications. This will enable the new use cases to provide access to other services within the network and from third-party service providers (SPs). End-users with their user equipment (UE) will be able to access services ubiquitously from multiple SPs that might share infrastructure and security management, whereby implementing security from one domain to another will be a challenge. This highlights a need for a new and effective security approach to address the security of such a complex system. This article proposes a network service security (NSS) modular framework for 5G and beyond that consists of different security levels of the network. It reviews the security issues of D2D communications in 5G, and it is used to address security issues that affect the users and SPs in an integrated and heterogeneous network such as the 5G enabled D2D communications network. The conceptual framework consists of a physical layer, network access, service and D2D security levels. Finally, it recommends security mechanisms to address the security issues at each level of the 5G-enabled D2D communications network.
Accuracy and Sensitivity of Clinical Parameters in Predicting Successful Extubation in Patients with Acute Brain Injury
Authors: Muzette Flávia Manhani , Lima Rayssa Bruna Holanda , de Araújo Silva Jennifer , Comin Thamara Ferro Balsani , Saraiva Erlandson Ferreira , Seki Karla Luciana Magnani , Christofoletti Gustavo
Published: July 2022

Background: Brain injuries are frequent causes of intubation and mechanical ventilation. The aim of this study was to investigate the accuracy and sensitivity of clinical parameters in predicting successful extubation in patients with acute brain injury. Methods: Six hundred and forty-four patients assisted at a high-complexity hospital were recruited. Patients were divided as for successful or failed extubation. The VISAGE score, maximum inspiratory and expiratory pressures, peak cough flow, and airway occlusion pressure at 0.1 s were used as predictors. Logistic regression analyses using ROC-curve identified values of accuracy and sensitivity. The Hosmer–Lemeshow test and the stepwise method calibrated the statistical model. Results: VISAGE score (odds ratio of 1.975), maximum inspiratory pressure (odds ratio of 1.024), and peak cough flow (odds ratio of 0.981) are factors consistent in distinguishing success from failure extubation. The ROC curve presented an accuracy of 79.7% and a sensitivity of 95.8%. Conclusions: VISAGE score, maximum inspiratory pressure and peak cough flow showed good accuracy and sensitivity in predicting successful extubation in patients with acute brain injury. The greater impact of VISAGE score indicates that patients’ neurological profile should be considered in association with ventilatory parameters in the decision of extubation.
The Influence of Maternal Vitamin D Supplementation in Pregnancies Associated with Preeclampsia: A Case-Control Study
Authors: Dahma George , Neamtu Radu , Nitu Razvan , Gluhovschi Adrian , Bratosin Felix , Grigoras Mirela Loredana , Silaghi Carmen , Citu Cosmin , Orlu Igwe Nwobueze , Bhattarai Sanket , Mocanu Adelina Geanina , Craina Marius , Bernad Elena
Published: July 2022

Preeclampsia is a pregnancy-specific illness that is hypothesized to occur due to vitamin D deficiency during pregnancy. Therefore, vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia and promoting neonatal well-being. The present study follows a case-control analysis that aims to determine the effect of vitamin D supplements on reducing the probability of recurrent preeclampsia. We identified 59 patients for the control group without vitamin D supplementation during pregnancy, while 139 patients were included in the cases group of pregnant women with a history of preeclampsia who confirmed taking daily vitamin D supplements in either 2000 UI or 4000 UI until the 36th week of pregnancy. There were 61 (80.3%) patients with a normal serum vitamin D level measured at 32 weeks in the pregnant women who took a daily dose of 4000 UI vitamin D and 43 (68.3%) in those who took a 2000 UI dose of vitamin D, compared to just 32 (54.2%) in those who did not take vitamin D at all. Regarding the blood pressure of pregnant women measured at 32 weeks, it was observed that 20.3% were hypertensive in the no supplementation group, compared to only 11.1% and 6.6% in those who were taking vitamin D during pregnancy (p-value = 0.049). Serum vitamin D levels at 32 weeks were measured at an average value of 23.9 ng/mL, compared with 28.4 ng/mL in the group taking a 2000 UI daily dose and 33.6 in those who supplemented with 4000 UI daily (p-value < 0.001). Proteinuria was identified more often in the group at risk for preeclampsia who did not take vitamin D supplements, while systolic blood pressure (p-value = 0.036) as well as diastolic blood pressure (p-value = 0.012), were all identified to have significantly higher values in the pregnant women with a history of preeclampsia that did not take vitamin D during the current pregnancy. The significant risk factors for preeclampsia development in pregnant patients at risk are: insufficient vitamin D serum levels (<20 ng/mL), OR = 2.52; no vitamin D supplementation, OR = 1.46; more than two pregnancies, OR = 1.89; gestational diabetes mellitus, OR = 1.66; and cardiovascular comorbidities, OR = 2.18. These findings imply that vitamin D has a role in the preservation of placental function and, therefore, in the prevention of the development of late preeclampsia. Pregnant mothers who supplemented their diets with vitamin D were protected against preeclampsia recurrence. Vitamin D supplementation during pregnancy may aid in the prevention of gestational hypertension and preeclampsia.
Trends in Physical Fitness and Nutritional Status among School-Aged Children and Adolescents during the COVID-19 Pandemic in Shaanxi, China—A Cross-Sectional Study
Authors: Lu Zijun , Mao Chuangui , Tan Yuanyuan , Zhang Xingyue , Li Zheng’ao , Zhang Ling , Zhu Wenfei , Sun Yuliang
Published: July 2022

Background: This study aimed to explore the characteristics of trends in physical fitness and nutritional status among school-aged students during the COVID-19 pandemic, which could help to develop targeted guidelines and policies for students (adolescents) to promote health during lockdowns resulting from public health emergencies. Methods: The physical fitness and nutritional status were measured from 2019 to 2021; the correlation between years and grade were analyzed. Results: a declining trend was found in aerobic fitness, strength fitness, speed fitness, and BMI during this lockdown. Conclusion: The changes in dietary behavior and the decrease in outdoor physical activities may be the reason for the decline. Furthermore, differences in subjects’ growth and limited space at home must be considered in the formulation of exercise and nutritional plans. According to the results of our study, exercise for aerobic fitness should receive more attention when students are enduring a pandemic lockdown. In addition, saying “no” to high-calorie foods in the form of snacking and ultra-processed food was the key to improving subjects’ nutritional status.
Synergistic Effect of β-Lapachone and Aminooxyacetic Acid on Central Metabolism in Breast Cancer
Authors: Chang Mario C. , Mahar Rohit , McLeod Marc A. , Giacalone Anthony G. , Huang Xiumei , Boothman David A. , Merritt Matthew E.
Published: July 2022

The compound β-lapachone, a naturally derived naphthoquinone, has been utilized as a potent medicinal nutrient to improve health. Over the last twelve years, numerous reports have demonstrated distinct associations of β-lapachone and NAD(P)H: quinone oxidoreductase 1 (NQO1) protein in the amelioration of various diseases. Comprehensive research of NQO1 bioactivity has clearly confirmed the tumoricidal effects of β-lapachone action through NAD+-keresis, in which severe DNA damage from reactive oxygen species (ROS) production triggers a poly-ADP-ribose polymerase-I (PARP1) hyperactivation cascade, culminating in NAD+/ATP depletion. Here, we report a novel combination strategy with aminooxyacetic acid (AOA), an aspartate aminotransferase inhibitor that blocks the malate-aspartate shuttle (MAS) and synergistically enhances the efficacy of β-lapachone metabolic perturbation in NQO1+ breast cancer. We evaluated metabolic turnover in MDA-MB-231 NQO1+, MDA-MB-231 NQO1−, MDA-MB-468, and T47D cancer cells by measuring the isotopic labeling of metabolites from a [U-13C]glucose tracer. We show that β-lapachone treatment significantly hampers lactate secretion by ~85% in NQO1+ cells. Our data demonstrate that combinatorial treatment decreases citrate, glutamate, and succinate enrichment by ~14%, ~50%, and ~65%, respectively. Differences in citrate, glutamate, and succinate fractional enrichments indicate synergistic effects on central metabolism based on the coefficient of drug interaction. Metabolic modeling suggests that increased glutamine anaplerosis is protective in the case of MAS inhibition.
Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China
Authors: Liu Zhaoshi , Tang Hao , Liang Haozheng , Bai Xiaoyin , Zhang Huimin , Yang Hong , Wang Hongying , Wang Li , Qian Jiaming
Published: July 2022

Background: Clinical data on the correlation of dyslipidaemia with the long-term outcomes of ulcerative colitis (UC) are limited. This study aimed to evaluate the impact of lipid levels on disease activity and prognosis in UC. Methods: The retrospective data of UC patients who had detailed lipid profiles were collected from January 2003 to September 2020. All patients were followed-up to 30 September 2021. The long-term outcomes were UC-related surgery and tumorigenesis. Results: In total, 497 patients were included in the analysis. Compared to patients with normal lipid levels, those with dyslipidaemia commonly presented with more serious disease activity. Low high-density lipoprotein cholesterol (p < 0.05) levels were associated with higher risks of severe disease activity in UC. Regarding the long-term outcomes, patients with persistent dyslipidaemia were at higher risks of UC-related surgery (HR: 3.27, 95% CI: 1.86–5.75, p < 0.001) and tumorigenesis (HR: 7.92, 95% CI: 3.97–15.78, p < 0.001) and had shorter surgery- and tumour-free survival (p < 0.001) than patients with transient dyslipidaemia and normal lipid levels. Low levels of high-density lipoprotein cholesterol (p < 0.001) and apolipoprotein A1 (p < 0.05) were associated with higher risks of surgery and tumorigenesis. Conclusion: Persistent dyslipidaemia was associated with a higher risk of serious disease activity and worse long-term outcomes among patients with UC. Lipid patterns should be assessed to improve the management of high-risk patients with UC in the early phase.
Modeling the Overdispersion of Pasteuria penetrans Endospores
Authors: Vagelas Ioannis , Leontopoulos Stefanos
Published: July 2022

This paper discusses a process of developing the data analysis and modeling of Pasteuria penetrans spore attachment in vitro and in planta, based on the observation that the number of spores attaching to juveniles within a given time increased by increasing the time of exposure to spores and the spores dose. Based on this, the P. penetrans spore attachment in vitro was modeled using the negative binomial distribution which permits decomposing the observation’s variability into three components: randomness, internal differences between individuals, and the presence of other external factors, e.g., the soil type. Additionally, we developed case-detection methods to explain P. penetrans spores’ attachment variability. The statistical methods developed in this paper show that a nematodes invasion is significant limited when second stage juveniles (J2s) are encumbered with seven P. penetrans spores. This research study concludes that the number of spores attached in J2s, the time of exposure of J2s to P. penetrans spores, and the soil texture are important factors affecting the invasion of root-knot nematodes in tomato plants.
The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides
Authors: Bege Miklós , Borbás Anikó
Published: July 2022

Nucleic acids play a central role in human biology, making them suitable and attractive tools for therapeutic applications. While conventional drugs generally target proteins and induce transient therapeutic effects, nucleic acid medicines can achieve long-lasting or curative effects by targeting the genetic bases of diseases. However, native oligonucleotides are characterized by low in vivo stability due to nuclease sensitivity and unfavourable physicochemical properties due to their polyanionic nature, which are obstacles to their therapeutic use. A myriad of synthetic oligonucleotides have been prepared in the last few decades and it has been shown that proper chemical modifications to either the nucleobase, the ribofuranose unit or the phosphate backbone can protect the nucleic acids from degradation, enable efficient cellular uptake and target localization ensuring the efficiency of the oligonucleotide-based therapy. In this review, we present a summary of structure and properties of artificial nucleic acids containing nucleobase, sugar or backbone modifications, and provide an overview of the structure and mechanism of action of approved oligonucleotide drugs including gene silencing agents, aptamers and mRNA vaccines.
Activation of Peripheral Cannabinoid Receptors Synergizes the Effect of Systemic Ibuprofen in a Pain Model in Rat
Authors: Díaz-Reval M. Irene , Cárdenas Yolitzy , Huerta Miguel , Trujillo Xóchitl , Sánchez-Pastor Enrique Alejandro , González-Trujano María Eva , Virgen-Ortíz Adolfo , Pérez-Hernández M. Gicela
Published: July 2022

Pharmacological synergism is a current strategy for the treatment of pain. However, few studies have been explored to provide evidence of the possible synergism between a non-steroidal anti-inflammatory drug (NSAID) and a cannabinoid agonist, in order to establish which combinations might be effective to manage pain. The aim of this study was to explore the synergism between ibuprofen (IBU) and the synthetic cannabinoid WIN 55,212-2 (WIN) to improve pain relief by analyzing the degree of participation of the CB1 and CB2 cannabinoid receptors in the possible antinociceptive synergism using an experimental model of pain in Wistar rats. First, the effective dose thirty (ED30) of IBU (10, 40, 80, and 160 mg/kg, subcutaneous) and WIN (3, 10, and 30 µg/p, intraplantar) were evaluated in the formalin test. Then, the constant ratio method was used to calculate the doses of IBU and WIN to be administered in combination (COMB) to determine the possible synergism using the isobolographic method. The participation of the CB1 and CB2 receptors was explored in the presence of the antagonists AM281 and AM630, respectively. The combination of these drugs produced a supra-additive response with an interaction index of 0.13. In addition, AM281 and AM630 antagonists reversed the synergistic effect in 45% and 76%, respectively, suggesting that both cannabinoid receptors are involved in this synergism, with peripheral receptors playing a relevant role. In conclusion, the combination of IBU + WIN synergism is mainly mediated by the participation of the CB2 receptor, which can be a good option for the better management of pain relief.
Immunogenicity of Current and New Therapies for Hemophilia A
Authors: Prezotti Alessandra N. L. , Frade-Guanaes Jéssica O. , Yamaguti-Hayakawa Gabriela G. , Ozelo Margareth C.
Published: July 2022

Anti-drug antibody (ADA) development is a significant complication in the treatment of several conditions. For decades, the mainstay of hemophilia A treatment was the replacement of deficient coagulation factor VIII (FVIII) to restore hemostasis, control, and prevent bleeding events. Recently, new products have emerged for hemophilia A replacement therapy, including bioengineered FVIII molecules with enhanced pharmacokinetic profiles: the extended half-life (EHL) recombinant FVIII products. However, the main complication resulting from replacement treatment in hemophilia A is the development of anti-FVIII neutralizing alloantibodies, known as inhibitors, affecting approximately 25–30% of severe hemophilia A patients. Therefore, the immunogenicity of each FVIII product and the mechanisms that could help increase the tolerance to these products have become important research topics in hemophilia A. Furthermore, patients with inhibitors continue to require effective treatment for breakthrough bleedings and procedures, despite the availability of non-replacement therapy, such as emicizumab. Herein, we discuss the currently licensed treatments available for hemophilia A and the immunogenicity of new therapies, such as EHL-rFVIII products, compared to other products available.
Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks
Authors: Sorrenti Vincenzo , Benedetti Francesca , Buriani Alessandro , Fortinguerra Stefano , Caudullo Giada , Davinelli Sergio , Zella Davide , Scapagnini Giovanni
Published: July 2022

Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one of the meaningful aspects of aging. Unsurprisingly, nutraceutical and pharmacological interventions could help maintain an optimal biological response by providing essential bioactive micronutrients required for the development, maintenance, and the expression of the immune response at all stages of life. In this regard, many studies have provided evidence of potential antiaging properties of resveratrol, as well as rapamycin and metformin. Indeed, in vitro and in vivo models have demonstrated for these molecules a number of positive effects associated with healthy aging. The current review focuses on the mechanisms of action of these three important compounds and their suggested use for the clinical treatment of immunosenescence and aging.
Discovery of Putative Dual Inhibitor of Tubulin and EGFR by Phenotypic Approach on LASSBio-1586 Homologs
Authors: Barbosa Gisele , Gelves Luis Gabriel Valdivieso , Costa Caroline Marques Xavier , Franco Lucas Silva , de Lima João Alberto Lins , Aparecida-Silva Cristiane , Teixeira John Douglas , Mermelstein Claudia dos Santos , Barreiro Eliezer J. , Lima Lidia Moreira
Published: July 2022

Combretastatin A-4 (CA-4, 1) is an antimicrotubule agent used as a prototype for the design of several synthetic analogues with anti-tubulin activity, such as LASSBio-1586 (2). A series of branched and unbranched homologs of the lead-compound 2, and vinyl, ethinyl and benzyl analogues, were designed and synthesized. A comparison between the cytotoxic effect of these homologs and 2 on different human tumor cell lines was performed from a cell viability study using MTT with 48 h and 72 h incubations. In general, the compounds were less potent than CA-4, showing CC50 values ranging from 0.030 μM to 7.53 μM (MTT at 72 h) and 0.096 μM to 8.768 μM (MTT at 48 h). The antimitotic effect of the target compounds was demonstrated by cell cycle analysis through flow cytometry, and the cellular mechanism of cytotoxicity was determined by immunofluorescence. While the benzyl homolog 10 (LASSBio-2070) was shown to be a microtubule stabilizer, the lead-compound 2 (LASSBio-1586) and the methylated homolog 3 (LASSBio-1735) had microtubule destabilizing behavior. Molecular docking studies were performed on tubulin protein to investigate their binding mode on colchicine and taxane domain. Surprisingly, the benzyl homolog 10 was able to modulate EGFR phosphorylate activity in a phenotypic model. These data suggest LASSBio-2070 (10) as a putative dual inhibitor of tubulin and EGFR. Its binding mode with EGFR was determined by molecular docking and may be useful in lead-optimization initiatives.
Intra-Domain Cysteines (IDC), a New Strategy for the Development of Original Antibody Fragment–Drug Conjugates (FDCs)
Authors: Jolivet Louis , Ait Mohamed Amar Imène , Horiot Catherine , Boursin Fanny , Colas Cyril , Letast Stéphanie , Denevault-Sabourin Caroline , Allard-Vannier Emilie , Joubert Nicolas , Aubrey Nicolas
Published: July 2022

Antibody–drug conjugates (ADCs) derived from a full immunoglobulin-G (IgG) are associated with suboptimal solid-tumor penetration and Fc-mediated toxicities. Antibody fragment–drug conjugates (FDCs) could be an alternative. Nevertheless, innovative solutions are needed to implant cysteines as conjugation sites in the single-chain fragment variable (scFv) format, which is the backbone from which many other antibody formats are built. In addition, the bioconjugation site has the utmost importance to optimize the safety and efficacy of bioconjugates. Our previous intra-tag cysteine (ITC) strategy consisted of introducing a bioconjugation motif at the C-terminal position of the 4D5.2 scFv, but this motif was subjected to proteolysis when the scFv was produced in CHO cells. Considering these data, using three intra-domain cysteine (IDC) strategies, several parameters were studied to assess the impact of different locations of a site-specific bioconjugation motif in the variable domains of an anti-HER2 scFv. In comparison to the ITC strategy, our new IDC strategy allowed us to identify new fragment–drug conjugates (FDCs) devoid of proteolysis and exhibiting enhanced stability profiles, better affinity, and better ability to kill selectively HER2-positive SK-BR-3 cells in vitro at picomolar concentrations. Thus, this work represents an important optimization step in the design of more complex and effective conjugates.
Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends
Authors: da Costa Nuno F. , Daniels Rolf , Fernandes Ana I. , Pinto João F.
Published: July 2022

The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome.