bluuebunny/crossref_metadata_2025 huggingface dataset:
Inference of Factors for Labor Productivity Growth Used Randomized Experiment and Statistical Causality
Authors: Orlova Ekaterina V.
Published: February 2023

The study of causal dependencies in economics is fraught with great difficulties, that it is required to consider not only the object structure, but also take into account a huge number of factors acting on the object, about which nothing is either known or difficult to measure. In this paper, we attempt to overcome this problem and apply the theory of statistical causality for labor productivity management. We suggest new technology that provides the inference of causal relations between the special programs implemented in the company’s and employee’s labor productivity. The novelty of the proposed technology is that it is based on a hybrid object model, combines two models: 1—the structural object model about its functioning and development to provide a causal inference and prediction the effect of explicit factors; 2—the model based on observed data to clarify causality and to test it empirically. The technology provides integration of the theory of causal Bayesian networks, methods of randomized controlled experiments and statistical methods, allows under nonlinearity, dynamism, stochasticity and non-stationarity of the initial data, to evaluate the effect of programs on the labor effeciency. The difference between the proposed technology and others is that it ensures determination the synergistic effect of the action of the cause (program) on the effect—labor productivity in condition of hidden factors. The practical significance of the research is the results of its testing the proposed theoretical provisions, methods and technologies on actual data about food service company. The results obtained could contribute to the labor productivity growth over uncertainty of the external and internal factors and provide the companies sustainable development and its profitability growth.
Unilateral Biportal Endoscopic Laminectomy for Treating Cervical Stenosis: A Technical Note and Preliminary Results
Authors: Zhu Chengyue , Zhou Xizhuo , Ge Guofen , Wang Cuijuan , Zhuang Xiaoshan , Cheng Wei , Wang Dong , Zhu Hang , Pan Hao , Zhang Wei
Published: February 2023

Objective: The objective of this study was to introduce a surgical technique for the percutaneous decompression of cervical stenosis (CS) using a unilateral biportal endoscopic approach and characterize its early clinical and radiographic results. Materials and Methods: Nineteen consecutive patients with CS who needed surgical intervention were recruited. All enrolled patients underwent unilateral biportal endoscopic laminectomy (UBEL). All patients were followed postoperatively for >1 year. The preoperative and final follow-up evaluations included the Japanese Orthopedic Association (JOA) score for neurological assessment, visual analogue scale (VAS) for axial pain and C2–C7 Cobb angle for cervical sagittal alignment. The postoperative complications were analyzed. Results: Thirteen males and six females were included in the analysis. The mean follow-up period was 16.3 ± 2.6 months. The mean operative time was 82.6 ± 18.4 min. Postoperative MRI and CT revealed ideal neural decompression of the treated segments in all patients. Preoperative VAS and JOA scores improved significantly after the surgery, and cervical lordosis was preserved on the postoperative images. Conclusions: UBEL was an effective surgical method for CS, which may also minimize iatrogenic damage to the posterior tension band (PTB) and help to maximize the preservation of the cervical lordosis.
An Investigation for Future Practice of Elective Hip and Knee Arthroplasties during COVID-19 in Romania
Authors: Moldovan Flaviu , Gligor Adrian , Moldovan Liviu , Bataga Tiberiu
Published: February 2023

Background and Objectives: Elective arthroplasty in Romania has been severely affected by the COVID-19 pandemic, and its effects are not quantified so far. The aim of this paper is to determine the impact of COVID-19 on arthroplasty interventions and how they varied in Romania. Materials and Methods: We performed a national retrospective analysis of patients who underwent primary and revision elective hip and knee interventions at the 120 orthopedic-traumatology hospitals in Romania that are registered in the National Endoprosthesis Registry from 1 January 2019 to 1 September 2022. First, we examined the monthly trend in the number of surgeries for seven categories of arthroplasties. We calculated the percentage change in the average number of cases per month and compared them with other types of interventions. We then examined the percentage change in the average monthly number of arthroplasty cases, relative to the number of COVID-19 cases reported nationwide, the influence of the pandemic on length of hospital stay, and the percentage of patients discharged at home who no longer follow recovery protocols. Finally, we calculated the impact of the pandemic on hospital revenues. Results: There was an abrupt decrease in the volume of primary interventions in hip and knee patients by up to 69.14% with a low degree of patient care, while the average duration of scheduled hospitalizations increased. We found a 1–2-day decrease in length of hospital stays for explored arthroplasties. We saw an increasing trend of home discharge, which was higher for primary interventions compared to revision interventions. The total hospital revenues were 50.96% lower in 2020 compared to 2019, and are currently increasing, with the 2022 estimate being 81.46%. Conclusions: The conclusion of this study is that the COVID-19 pandemic severely affected the volume of arthroplasty of the 120 hospitals in Romania, which also had unfavorable financial implications. We proposed the development of new procedures and alternative clinical solutions, as well as personalized home recovery programs, to be activated if necessary, for possible future outbreaks.
Calcium Alginate Production through Forward Osmosis with Reverse Solute Diffusion and Mechanism Analysis
Authors: Cao Da-Qi , Tang Kai , Zhang Wen-Yu , Chang Cheng , Han Jia-Lin , Tian Feng , Hao Xiao-Di
Published: February 2023

Calcium alginate (Ca-Alg) is a novel target product for recovering alginate from aerobic granular sludge. A novel Ca-Alg production method was proposed herein where Ca-Alg was formed in a sodium alginate (SA) feed solution (FS) and concentrated via forward osmosis (FO) with Ca2+ reverse osmosis using a draw solution of CaCl2. An abnormal reverse solute diffusion was observed, with the average reverse solute flux (RSF) decreasing with increasing CaCl2 concentrations, while the average RSF increased with increasing alginate concentrations. The RSF of Ca2+ in FS decreased continuously as the FO progressed, using 1.0 g/L SA as the FS, while it increased initially and later decreased using 2.0 and 3.0 g/L SA as the FS. These results were attributed to the Ca-Alg recovery production (CARP) formed on the FO membrane surface on the feed side, and the percentage of Ca2+ in CARP to total Ca2+ reverse osmosis reached 36.28%. Scanning electron microscopy and energy dispersive spectroscopy also verified CARP existence and its Ca2+ content. The thin film composite FO membrane with a supporting polysulfone electrospinning nanofiber membrane layer showed high water flux and RSF of Ca2+, which was proposed as a novel FO membrane for Ca-Alg production via the FO process with Ca2+ reverse diffusion. Four mechanisms including molecular sieve role, electrification of colloids, osmotic pressure of ions in CARP, and FO membrane structure were proposed to control the Ca-Alg production. Thus, the results provide further insights into Ca-Alg production via FO along with Ca2+ reverse osmosis.
Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review
Authors: Laurindo Lucas Fornari , de Maio Mariana Canevari , Minniti Giulia , de Góes Corrêa Natália , Barbalho Sandra Maria , Quesada Karina , Guiguer Elen Landgraf , Sloan Kátia Portero , Detregiachi Claudia R. P. , Araújo Adriano Cressoni , de Alvares Goulart Ricardo
Published: February 2023

Inflammatory bowel diseases (IBDs) are related to nuclear factor erythroid 2-related factor 2 (Nrf2) dysregulation. In vitro and in vivo studies using phytocompounds as modulators of the Nrf2 signaling in IBD have already been published. However, no existing review emphasizes the whole scenario for the potential of plants and phytocompounds as regulators of Nrf2 in IBD models and colitis-associated colorectal carcinogenesis. For these reasons, this study aimed to build a review that could fill this void. The PubMed, EMBASE, COCHRANE, and Google Scholar databases were searched. The literature review showed that medicinal plants and phytochemicals regulated the Nrf2 on IBD and IBD-associated colorectal cancer by amplifying the expression of the Nrf2-mediated phase II detoxifying enzymes and diminishing NF-κB-related inflammation. These effects improve the bowel environment, mucosal barrier, colon, and crypt disruption, reduce ulceration and microbial translocation, and consequently, reduce the disease activity index (DAI). Moreover, the modulation of Nrf2 can regulate various genes involved in cellular redox, protein degradation, DNA repair, xenobiotic metabolism, and apoptosis, contributing to the prevention of colorectal cancer.
Design of Spectrum Processing Chiplet Based on FFT Algorithm
Authors: Meng Baoping , Shan Guangbao , Zheng Yanwen
Published: February 2023

With the rapid development of electronic information and computer science, the fast Fourier transform (FFT) has played an increasingly important role in digital signal processing (DSP). This paper presented a spectrum processing chiplet design method to solve slow speed, low precision, and low resource utilization in spectrum processing of general-purpose spectrum chips and field programmable gate array (FPGA). To realize signal processing, the Radix-2 4096-point FFT algorithm with pipeline structure is used to process spectral signals extracted from the time domain. To reduce the harm caused by spectrum leakage, a windowing module is added to optimize the input data, and the clock gating unit (CGU) is used to perform low-power management on the entire clock reset. The result shows the chiplet takes 0.368 ms to complete a 4096-point frequency sweep under a clock frequency of 61.44 MHz. The chiplet significantly improves speed and accuracy in spectrum processing, which has great application potential in wireless communication.
Associations of Microbial Diversity with Age and Other Clinical Variables among Pediatric Chronic Rhinosinusitis (CRS) Patients
Authors: Lim Shen Jean , Jithpratuck Warit , Wasylik Kathleen , Sriaroon Panida , Dishaw Larry J.
Published: February 2023

Chronic rhinosinusitis (CRS) is a heterogenous disease that causes persistent paranasal sinus inflammation in children. Microorganisms are thought to contribute to the etiology and progression of CRS. Culture-independent microbiome analysis offers deeper insights into sinonasal microbial diversity and microbe–disease associations than culture-based methods. To date, CRS-related microbiome studies have mostly focused on the adult population, and only one study has characterized the pediatric CRS microbiome. In this study, we analyzed the bacterial diversity of adenoid tissue, adenoid swab, maxillary sinus, and sinus wash samples from 45 pediatric CRS patients recruited from the Johns Hopkins All Children’s Hospital (JHACH) in St. Petersburg, FL, USA. The alpha diversity in these samples was associated with baseline nasal steroid use, leukotriene receptor antagonist (LTRA) use, and total serum immunoglobulin (Ig) E (IgE) level. Streptococcus, Moraxella, and Haemophilus spp. were most frequently identified from sinus cultures and the sequenced 16S rRNA gene content. Comparative analyses combining our samples with the samples from the previous microbiome study revealed differentially abundant genera between patients with pediatric CRS and healthy controls, including Cutibacterium and Moraxella. Additionally, the abundances of Streptobacillus and Staphylococcus were consistently correlated with age in both adenoid- and sinus-derived samples. Our study uncovers new associations of alpha diversity with clinical parameters, as well as associations of specific genera with disease status and age, that can be further investigated.
Epidemiology and Drug Resistance Patterns of Mycobacterium tuberculosis in High-Burden Area in Western Siberia, Russia
Authors: Kostyukova Irina , Pasechnik Oksana , Mokrousov Igor
Published: February 2023

Russia is a high-burden area for multidrug-resistant tuberculosis (MDR-TB). Here, we studied the epidemiological situation and drug resistance patterns of Mycobacterium tuberculosis in the Omsk region in Western Siberia. M. tuberculosis isolates (n = 851) were recovered from newly diagnosed TB patients in 2021. The isolates were tested by bacteriological and molecular methods, and long-term epidemiological data were analyzed. The TB incidence dec, this is not variablereased from 93.9 in 2012 to 48.1 in 2021, per 100,000 population, but the primary MDR-TB rate increased from 19.2% to 26.4%. The destructive forms of tuberculosis accounted for 37.8% of all cases, while 35.5% of patients were smear-positive. Of all isolates tested, 55.2% were culture-positive, of which 94.5% were further tested for phenotypic drug resistance and associated mutations. More than half (53.4%) of isolates were drug-resistant, 13.9% were monoresistant and 67.9% were MDR. Among MDR isolates, 40.4% were pre-XDR, and 19.2% were XDR. The spectrum of drug resistance included second-line drugs (new-generation fluoroquinolones, linezolid), which significantly increase the risk of an adverse outcome in patients. In conclusion, our results highlight the critical importance of monitoring drug resistance in circulating M. tuberculosis strains emerging due to ineffective treatment and active transmission.
Diversity and Composition of Culturable Microorganisms and Their Biodeterioration Potentials in the Sandstone of Beishiku Temple, China
Authors: Zhang Yong , Su Min , Wu Fasi , Gu Ji-Dong , Li Jie , He Dongpeng , Guo Qinglin , Cui Huiping , Zhang Qi , Feng Huyuan
Published: February 2023

Microbial colonization on stone monuments leads to subsequent biodeterioration; determining the microbe diversity, compositions, and metabolic capacities is essential for understanding biodeterioration mechanisms and undertaking heritage management. Here, samples of epilithic biofilm and naturally weathered and exfoliated sandstone particles from different locations at the Beishiku Temple were collected to investigate bacterial and fungal community diversity and structure using a culture-based method. The biodeterioration potential of isolated fungal strains was analyzed in terms of pigmentation, calcite dissolution, organic acids, biomineralization ability, and biocide susceptibility. The results showed that the diversities and communities of bacteria and fungi differed for the different sample types from different locations. The population of culturable microorganisms in biofilm samples was more abundant than that present in the samples exposed to natural weathering. The environmental temperature, relative humidity, and pH were closely related to the variation in and distribution of microbial communities. Fungal biodeterioration tests showed that isolated strains four and five were pigment producers and capable of dissolving carbonates, respectively. Their biomineralization through the precipitation of calcium oxalate and calcite carbonate could be potentially applied as a biotechnology for stone heritage consolidation and the mitigation of weathering for monuments. This study adds to our understanding of culturable microbial communities and the bioprotection potential of fungal biomineralization.
Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors
Authors: Chen Jinwei , Xu Likun , Wang Baogang , Zhang Dongna , Zhao Liangliang , Bei Zhuchun , Song Yabin
Published: February 2023

The Lassa virus (LASV) causes Lassa fever, a highly infectious and lethal agent of acute viral hemorrhagic fever. At present, there are still no effective treatments available, creating an urgent need to develop novel therapeutics. Some benzimidazole compounds targeting the arenavirus envelope glycoprotein complex (GPC) are promising inhibitors of LASV. In this study, we synthesized two series of LASV inhibitors based on the benzimidazole structure. Lentiviral pseudotypes bearing the LASV GPC were established to identify virus entry inhibitors. Surface plasmon resonance (SPR) was further used to verify the binding activities of the potential compounds. Compounds 7d−Z, 7h−Z, 13c, 13d, and 13f showed relatively excellent antiviral activities with IC50 values ranging from 7.58 to 15.46 nM and their SI values above 1251. These five representative compounds exhibited stronger binding affinity with low equilibrium dissociation constants (KD < 8.25 × 10−7 M) in SPR study. The compound 7h−Z displayed the most potent antiviral activity (IC50 = 7.58 nM) with a relatively high SI value (2496), which could be further studied as a lead compound. The structure–activity relationship indicated that the compounds with lipophilic and spatially larger substituents might possess higher antiviral activity and a much larger safety margin. This study will provide some good guidance for the development of highly active compounds with a novel skeleton against LASV.
Coco Monoethanolamide Surfactant as a Sustainable Corrosion Inhibitor for Mild Steel: Theoretical and Experimental Investigations
Authors: Ganjoo Richika , Sharma Shveta , Sharma Praveen K. , Dagdag O. , Berisha Avni , Ebenso Eno E. , Kumar Ashish , Verma Chandrabhan
Published: February 2023

Recent studies indicate that surfactants are a relatively new and effective class of corrosion inhibitors that almost entirely meet the criteria for a chemical to be used as an aqueous phase corrosion inhibitor. They possess the ideal hydrophilicity to hydrophobicity ratio, which is crucial for effective interfacial interactions. In this study, a coconut-based non-ionic surfactant, namely, coco monoethanolamide (CMEA), was investigated for corrosion inhibition behaviour against mild steel (MS) in 1 M HCl employing the experimental and computational techniques. The surface morphology was studied employing the scanning electron microscope (SEM), atomic force microscope (AFM), and contact measurements. The critical micelle concentration (CMC) was evaluated to be 0.556 mM and the surface tension corresponding to the CMC was 65.28 mN/m. CMEA manifests the best inhibition efficiency (η%) of 99.01% at 0.6163 mM (at 60 °C). CMEA performs as a mixed-type inhibitor and its adsorption at the MS/1 M HCl interface followed the Langmuir isotherm. The theoretical findings from density functional theory (DFT), Monte Carlo (MC), and molecular dynamics (MD) simulations accorded with the experimental findings. The MC simulation’s assessment of CMEA’s high adsorption energy (−185 Kcal/mol) proved that the CMEA efficiently and spontaneously adsorbs at the interface.
Nucleotide Imbalance, Provoked by Downregulation of Aspartate Transcarbamoylase Impairs Cold Acclimation in Arabidopsis
Authors: Bellin Leo , Garza Amaya Diana Laura , Scherer Vanessa , Pruß Tobias , John Annalisa , Richter Andreas , Möhlmann Torsten
Published: February 2023

Aspartate transcarbamoylase (ATC) catalyzes the first committed step in pyrimidine de novo synthesis. As shown before, mutants with 80% reduced transcript and protein levels exhibit reduced levels of pyrimidine metabolites and thus nucleotide limitation and imbalance. Consequently, reduced photosynthetic capacity and growth, accompanied by massive transcriptional changes, were observed. Here, we show that nucleotide de novo synthesis was upregulated during cold acclimation of Arabidopsis thaliana (ecotype Columbia, Col-0) plants, but ATC knockdown mutants failed to acclimate to this condition as they did not accumulate neutral sugars and anthocyanins. A global transcriptome analysis revealed that most of the transcriptional changes observed in Col-0 plants upon cold exposure were also evident in ATC knockdown plants. However, several responses observed in cold-treated Col-0 plants could already be detected in knockdown plants when grown under standard conditions, suggesting that these mutants exhibited typical cold responses without prior cold stimulation. We believe that nucleotide signaling is involved in “cold-like priming” and “cold acclimation” in general. The observed transcript levels of genes involved in central carbon metabolism and respiration were an exception to these findings. These were upregulated in the cold but downregulated in warm-grown ATC mutants.
Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches
Authors: Mahnashi Mater H. , Alam Waqas , Huneif Mohammed A. , Abdulwahab Alqahtani , Alzahrani Mohammed Jamaan , Alshaibari Khaled S. , Rashid Umar , Sadiq Abdul , Jan Muhammad Saeed
Published: February 2023

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.
DIA-MS Based Proteomics Combined with RNA-Seq Data to Unveil the Mitochondrial Dysfunction in Human Glioblastoma
Authors: Zeng Hao-Long , Hu Lizhi , Chen Xi , Han Qiang-Qiang , Li Huijun , Cheng Liming , Li Chao-Xi
Published: February 2023

Mitochondrial dysfunctions underlie the pathogenesis in glioblastoma multiforme (GBM). Comprehensive proteomic profiling of mitochondria-specific changes in human GBM is still insufficient. This study carried out a DIA-MS based proteomic analysis on the mitochondria isolated from human primary GBM and peritumoral tissue (as paired control), and further compared those findings with the transcriptomic datasets. A total of 538 mitochondrion-specific proteins were rigorously confirmed, among which 190 differentially expressed proteins were identified. Co-regulations of the mitochondrial dysfunction pathway networks were observed, including significant up-regulations of mitochondrial translation and apoptosis, as well as down-regulations of OXPHOS and mitochondrial dynamics. Proteins related to FA, AA metabolism and ROS also showed significant variations. Most of these alterations were consistent in trend when compared the proteomics findings with the RNA-Seq datasets, while the changes at protein levels appeared to be more dramatic. Potentially key proteins in GBM were identified, including up-regulated pro-apoptotic protein CASP3, BAX, fatty acid oxidation enzymes CPT1A, CPT2, ACADM, serine-glycine enzymes SHMT2, GATM, ROS-related protein SOD2, GPX1, and CAT; and down-regulated dynamin-related protein MFN1, MFN2, OPA1, and OXPHOS components; and also several differentially expressed ALDH isoforms. This study systematically profiled the mitochondrial dysfunctions by combining proteomic findings and mRNA datasets, which would be a valuable resource to the community for further thorough analyses.
In-Depth Insight into the Ag/CNQDs/g-C3N4 Photocatalytic Degradation of Typical Antibiotics: Influence Factor, Mechanism and Toxicity Evaluation of Intermediates
Authors: Li Chen , Sun Tianyi , Yi Guohui , Zhang Dashuai , Zhang Yan , Lin Xiaoxue , Liu Jinrui , Shi Zaifeng , Lin Qiang
Published: February 2023

In this paper, the photocatalytic degradation efficiency of typical antibiotics (norfloxacin (NOR), sulfamethoxazole (SMX) and tetracycline hydrochloride (TCH)) by Ag/CNQDs/g-C3N4 under visible light irradiation was studied. Various strategies were applied to characterize the morphology, structure and photochemical properties of the Ag/CNQDs/g-C3N4 composites. The superior photocatalytic activity of Ag/CNQDs/g-C3N4 was attributed to the wide light response range and the enhancement of interfacial charge transfer. At the same time, the effect of the influence factors (pH, Humic acid (HA) and coexisting ions) on the antibiotics degradation were also investigated. Furthermore, the electron spin resonance (ESR) technology, free radical quenching experiments, LC/MS and DFT theoretical calculations were applied to predict and identify the active groups and intermediates during the photocatalytic degradation process. In addition, Ag/CNQDs/g-C3N4 exhibited the obvious antibacterial effect to Escherichia coli due to the addition of Ag NPs. This study develops a new way for the removal of emerging antibiotic pollution from wastewaters.
Oxidative Stability of Cottonseed Butter Products under Accelerated Storage Conditions
Authors: He Zhongqi , Nam Sunghyun , Klasson K. Thomas
Published: February 2023

Cottonseed is a natural product of cotton (Gossypium spp.) crops. This work evaluated the oxidative stability of cottonseed butters through accelerated autoxidation by storage at 60 °C for 25 days. Three oxidative stability parameter values (peroxide value, p-anisidine value, and total oxidation value) were monitored over the storage time. These chemical measurements revealed that the storage stability of the butter products was dominated by primary oxidation of lipid (oil) components, while the secondary oxidation levels were relatively unchanged over the storage time. An analysis of the tocopherols (natural oxidants in cottonseed) suggested not only the protection function of the molecules against oxidation of the cottonseed butter during storage, but also the dynamic mechanism against the primary oxidation of lipid components. Attenuated total reflectance–Fourier-transform infrared spectroscopy (ATR–FTIR) data confirmed no changes in the major C functional groups of cottonseed butters over the storage time. On the other hand, characteristic minor peaks of conjugated dienes and trienes related to lipid oxidation were impacted by the accelerated storage. As each day of accelerated oxidation at 60 °C is equivalent to 16 days of storage at 20 °C, observations in this work should have reflected the oxidative stability behaviors of the cottonseed butters after about 13 months of shelf storage under ambient storage conditions. Thus, these data that were collected under the accelerated oxidation testing would be useful not only to create a better understanding of the autooxidation mechanism of lipid molecules in cottonseed butters, but also in developing or recommending appropriate storage conditions for cottonseed end products to prevent them from quality degradation.
Migration: A Neglected Potential Contribution of HCl-Oxidized Au(0)
Authors: Zhang Zilong , Zhang Haifeng , Wang Bolin , Yue Yuxue , Zhao Jia
Published: February 2023

In this study, the typical oxidation process of Au/C catalysts exposed to HCl is presented. Although the process violates the standard electrode potentials, the “oxidized” tendency of Au(0) species is analyzed. This oxidation behavior can only be triggered over the Au/C sample within residual cationic Au species, and terminated over the completely metallic Au(0)/C sample. This study demonstrates that the presence of surface chlorination species cannot facilitate the oxidation of Au(0) and Au(I) when the sample is treated with HCl alone, which excludes the oxidation paths of: Au(0) → Au(III) and Au(I) → Au(III). The reported “HCl-oxidized Au(0)” behavior is partially caused by the migration of Au(III) species in the carbon bulk-phase, which occurs outside the XPS detection limit region and into the detection limit rather than the “HCl-oxidized Au(0)” itself. The mechanism of driving the bulk-phase Au(III) migrated from the steady destabilized state to the carbon surface is then studied. This study demonstrates that the migration of Au cannot be neglected behind the curious oxidation phenomenon by HCl, which provides a new perspective for the oxidation of other noble metals by HCl.
Identification of the Putative Binding Site of a Benzimidazole Opioid (Etazene) and Its Metabolites at µ-Opioid Receptor: A Human Liver Microsomal Assay and Systematic Computational Study
Authors: Chaturvedi Krishna , Hewamanna Isuru , Pandey Pankaj , Khan Washim , Wang Yan-Hong , Chittiboyina Amar , Doerksen Robert , Godfrey Murrell
Published: February 2023

The synthetic benzimidazole opioid etazene (which has a 70-times higher analgesic activity than morphine), a recreational drug, has gained popularity as a novel psychoactive substance (NPS) on the illegal/darknet market; however, no experimental information is available at the molecular level on the binding mechanism and putative binding site of etazene and its metabolites at the µ-opioid receptor (MOR). In the present study, we investigated the metabolism of etazene in human liver microsomes using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC–MS). We also explored the possibilities of MOR activation by etazene and its metabolites by studying their binding mechanisms and interaction profiles at an active-state MOR model via molecular docking, binding free energy calculations, and all-atom molecular dynamics (MD) simulations. The putative metabolites of etazene were also predicted using the ADMET Predictor 10.1. The molecular docking studies and free energy calculations showed that etazene and its metabolites (M1, M2, and M5–M7) exhibited strong predicted binding affinity at MOR and showed overlapped binding orientation with MOR-bound agonist BU72, which was co-crystallized in the MOR X-ray crystal structure (PDB ID: 5C1M). MD also confirmed the stability of the MOR–etazene and MOR–M6 complexes. These results suggest that etazene and its metabolites may act as strong MOR agonists, highlighting the necessity of experimental validation. The insights from this study, such as key interactions between etazene and its metabolites and the MOR, will allow authorities to predict potential analogs and clarify the target–protein interactions associated with this illicit substance, granting advanced or rapid reactions to confiscating or banning potential emerging drugs.
Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism
Authors: Raish Mohammad , Ahmad Ajaz , Shahid Mudassar , Jardan Yousef A. Bin , Ahad Abdul , Kalam Mohd Abul , Ansari Mushtaq Ahmad , Iqbal Muzaffar , Ali Naushad , Alkharfy Khalid M. , Al-Jenoobi Fahad I.
Published: February 2023

Dasatinib (DAS), a narrow-therapeutic index drug, Bcr-Abl, and Src family kinases multitarget inhibitor have been approved for chronic myelogenous leukemia (CML) and Ph-positive acute lymphocytic leukemia (Ph+ ALL). Apigenin (APG) has a long history of human usage in food, herbs, health supplements, and traditional medicine, and it poses low risk of damage. The concomitant use of APG containing herbs/foods and traditional medicine may alter the pharmacokinetics of DAS, that probably lead to possible herb–drug interactions. The pharmacokinetic interaction of APG pretreatment with DAS in rat plasma following single and co-oral dosing was successfully deliberated using the UPLC–MS/MS method. The in vivo pharmacokinetics and protein expression of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 demonstrate that APG pretreatment has potential to drastically changed the DAS pharmacokinetics where escalation in the Cmax, AUC(0–t), AUMC(0-inf_obs), T1/2, Tmax, and MRT and reduction in Kel, Vd, and Cl significantly in rats pretreated with APG 40 mg/kg, thus escalating systemic bioavailability and increasing the rate of absorption via modulation of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 protein expression. Therefore, the concomitant consumption of APG containing food or traditional herb with DAS may cause serious life-threatening drug interactions and more systematic clinical study on herb–drug interactions is required, as well as adequate regulation in herbal safety and efficacy.
Evaluation of the Cytotoxic, Antioxidative and Antimicrobial Effects of Dracocephalum moldavica L. Cultivars
Authors: Simea Ștefania , Ielciu Irina , Hanganu Daniela , Niculae Mihaela , Pall Emoke , Burtescu Ramona Flavia , Olah Neli-Kinga , Cenariu Mihai , Oniga Ilioara , Benedec Daniela , Duda Marcel
Published: February 2023

The aim of the present study was to correlate the antioxidant, antimicrobial, and cytotoxic activities of hydroalcoholic extracts obtained from the aerial parts of three Dracocephalum moldavica L. cultivars with their polyphenolic compositions. The polyphenols were identified and quantified using spectrophotometrical methods and LC–MS analysis. Their antioxidant capacities were assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. Their in vitro antimicrobial efficacies were assessed using the agar well diffusion and broth microdilution methods. Their cytotoxicity was investigated on normal diploid foreskin fibroblasts (BJ) and on colorectal adenocarcinoma (DLD-1) cell lines. The results pointed out significant amounts of polyphenolic compounds in the compositions of the tested cultivars, with rosmarinic acid as the main compound (amounts ranging between 5.337 ± 0.0411 and 6.320 ± 0.0535 mg/mL). All three cultivars displayed significant antioxidant (IC50 ranging between 35.542 ± 0.043 and 40.901 ± 0.161 µg/mL for the DPPH assay, and for the FRAP assay 293.194 ± 0.213 and 330.165 ± 0.754 µmol Trolox equivalent/mg dry vegetal material) and antimicrobial potential (especially towards the Gram-positive bacteria), as well as a selective toxicity towards the tumoral line. A significant positive correlation was found between antioxidant activity and the total phenolic acids (r2 = 0.987) and polyphenols (r2 = 0.951). These findings bring further arguments for strongly considering D. moldavica cultivars as promising vegetal products, which warrants further investigation.
Analyses of Transcriptomics upon IL-1β-Stimulated Mouse Chondrocytes and the Protective Effect of Catalpol through the NOD2/NF-κB/MAPK Signaling Pathway
Authors: Pang Yong , Zhao Lu , Ji Xueyan , Guo Kaijin , Yin Xiaoxing
Published: February 2023

The overall objective of this study was to investigate the mechanism of inflammation on chondrocyte injury and the protective effect of catalpol on chondrocytes in an inflammatory environment. Chondrocytes were isolated and cultured from the knee joints of three-day-old newborn mice. Alcian Blue staining and the immunocytochemistry staining of type II collagen were used to identify the purity of chondrocytes. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) and subjected to transcriptome analysis. Differentially expressed genes (DEGs) were further analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In this experimental study, we performed the viability assay to determine the effects of different concentrations of catalpol on the cell viability of chondrocytes. Chondrocytes were seeded in six-well plates and exposed to 10 μM catalpol 2 h prior to treatment with IL-1β (10 ng/mL). Quantitative real-time (qPCR) and Western blotting were performed to evaluate the RNA and protein expression, respectively. Based on the results of transcriptomics analysis, we found the NOD2 signaling pathway, the NF-kappa B signaling pathway, and the MAPK signaling pathway showed significant changes in chondrocyte damage caused by inflammation. Catalpol (10 μM and 100 μM) could significantly reduce NO, IL-6, IL-1β, and TNF-α in supernatant of chondrocytes. Catalpol significantly inhibited the mRNA expression of IL-1, IL-6, and IL-12 in chondrocytes induced by IL-1β. Catalpol markedly inhibited MMP3, MMP13 mRNA, and protein levels. Catalpol could significantly reduce TNF-α mRNA levels in inflammatory chondrocytes. Inflammation causes significant increases in mRNA levels and protein levels of NOD2, mRNA levels, and protein levels were markedly suppressed by catalpol. In addition, catalpol could significantly increase IKBα protein levels and significantly lower intranuclear P65 levels. Catalpol significantly lowered the phosphorylation protein levels of ERK, p38, and JNK. Our transcriptomic analysis demonstrated that the activation of NOD2 and its downstream pathways, NF-κB and MAPK, is an important cause of the inflammatory injury to chondrocytes induced by IL-1β. Catalpol inhibited the activation of the NOD2 signaling pathway, which reduced the phosphorylation of ERK, p38, and JNK, inhibited the degradation of IκBα, inhibited p65 translocation into the nucleus, reduced the release of inflammatory cytokines, and attenuated the inflammatory damage to chondrocytes.
Quality Assessment of Burdekin Plum (Pleiogynium timoriense) during Ambient Storage
Authors: Chen Gengning , Netzel Michael E. , Mantilla Sandra Milena Olarte , Phan Anh Dao Thi , Netzel Gabriele , Sivakumar Dharini , Sultanbawa Yasmina
Published: February 2023

Pleiogynium timoriense, commonly known as Burdekin plum (BP), is among many Australian native plants traditionally used by Indigenous people. However, only limited information is available on the nutritional and sensory quality of BP grown in Australia as well as its changes during storage. Therefore, this study evaluated the quality of BP during one week of ambient storage (temperature 21 °C, humidity 69%). Proximate analysis revealed a relatively high dietary fiber content in BP (7–10 g/100 g FW). A significant reduction in fruit weight and firmness (15–30% and 60–90%, respectively) with distinguishable changes in flesh color (ΔE > 3) and an increase in total soluble solids (from 11 to 21 °Brix) could be observed during storage. The vitamin C and folate contents in BP ranged from 29 to 59 mg/100g FW and 0.3 to 5.9 μg/100g FW, respectively, after harvesting. A total phenolic content of up to 20 mg GAE/g FW and ferric reducing antioxidant power of up to 400 μmol Fe2+/g FW in BP indicate a strong antioxidant capacity. In total, 34 individual phenolic compounds were tentatively identified in BP including cyanidin 3-galactoside, ellagic acid and gallotannins as the main phenolics. Principle component analysis (PCA) of the quantified phenolics indicated that tree to tree variation had a bigger impact on the phenolic composition of BP than ambient storage. Sensory evaluation also revealed the diversity in aroma, appearance, texture, flavor and aftertaste of BP. The results of this study provide crucial information for consumers, growers and food processors.
N-Feruloyl Serotonin Attenuates Neuronal Oxidative Stress and Apoptosis in Aβ25–35-Treated Human Neuroblastoma SH-SY5Y Cells
Authors: He Meitong , Park Chanhum , Shin Yusu , Kim Jihyun , Cho Eunju
Published: February 2023

Amyloid-beta (Aβ) aggregation and deposition have been identified as a critical feature in the pathology of Alzheimer’s disease (AD), with a series of functional alterations including neuronal oxidative stress and apoptosis. N-feruloyl serotonin (FS) is a plant-derived component that exerts antioxidant activity. This study investigated the protective effects of FS on Aβ25–35-treated neuronal damage by regulation of oxidative stress and apoptosis in human neuroblastoma SH-SY5Y cells. The radical scavenging activities increased with the concentration of FS, exhibiting in vitro antioxidant activity. The Aβ25–35-treated SH-SY5Y cells exerted neuronal cell injury by decreased cell viability and elevated reactive oxygen species, but that was recovered by FS treatment. In addition, treatment of FS increased anti-apoptotic factor B-cell lymphoma protein 2 (Bcl-2) and decreased the pro-apoptotic factor Bcl-2-associated X protein. The FS attenuated Aβ-stimulated neuronal apoptosis by regulations of mitogen-activated protein kinase signaling pathways. Moreover, activated CREB-BDNF signaling was observed by the treatment of FS in Aβ25–35-induced SH-SY5Y cells. These results demonstrate that FS shows potential neuroprotective effects on Aβ25–35-induced neuronal damage by attenuation of oxidative stress and apoptosis, and suggest that FS may be considered a promising candidate for the treatment of AD.
Anemoside A3 Inhibits Macrophage M2-Like Polarization to Prevent Triple-Negative Breast Cancer Metastasis
Authors: Liu Peng , Liu Yahui , Chen Lanying , Fan Zeping , Luo Yingying , Cui Yaru
Published: February 2023

Triple negative breast cancer (TNBC) exhibits the characteristics of strong metastatic ability and a high recurrence rate, and M2-type macrophages play an important role in this process. Previous research data suggested that Anemoside A3 (A3), a monomeric component of Pulsatilla Chinensis, could prevent and treat TNBC by converting M0 macrophages into M1 immunogen phenotypes. This study showed that A3 significantly restrained the lung metastases of 4 T1-Luc cells with bioluminescence imaging in vivo and Hematoxylin and Eosin (H&E) staining. Meanwhile, the percentage of M2-type macrophages (CD206+ labeled cells) in the lung tissues was evidently decreased through immunohistochemical assay. We further proved that A3 markedly prevented M2-type polarization induced by IL-4 in vitro, as illustrated by the down-regulated expression of the cell surface marker CD206 protein by FACS and Arg-1, and of the Fizz1 and Ym1 genes by RT-PCR in M2-type macrophages. Furthermore, the invasion and migration of 4 T1 cells, which was promoted by the conditioned medium from M2-type macrophages, could be suppressed by A3. Luminex assay demonstrated that A3 treatment resulted in a reduction of the levels of CCL2, VEGF, CCL7, and MMP-9 in conditioned medium. Additionally, the expression of phosphorylated-STAT3 protein was inhibited by A3, which resulted in the macrophage M2-type polarization arrest, while no significant difference in JAK2 phosphorylation was detected. SiRNA transfection experiments suggested that STAT3 might be the target of A3 inhibiting M2-type polarization of macrophages. In conclusion, these results indicate that A3 could attenuate the metastasis of TNBC by inhibiting the M2-type polarization of macrophages, which may be related to the STAT3 pathway.
Preliminary Air Quality and Microclimatic Conditions Study in the Santuario della Beata Vergine dei Miracoli in Saronno (VA)
Authors: Bergomi Andrea , Comite Valeria , Guglielmi Vittoria , Borelli Mattia , Lombardi Chiara Andrea , Bonomi Roberto , Pironti Concetta , Ricciardi Maria , Proto Antonio , Mariani Carlo , Fermo Paola
Published: February 2023

In the present work, the microclimatic conditions (temperature (T), relative humidity (RH), and illuminance (I)), together with the air quality (both aerosol particulate matter (PM) and gaseous pollutants), were monitored to evaluate the environmental conditions inside the Santuario della Beata Vergine dei Miracoli in Saronno (VA), a masterpiece of the Italian Renaissance. For this purpose, dataloggers were used to carry out the T, RH, and I measurements, whereas an optical particle counter (OPC) was employed to perform the particle count and determine the concentration of the aerosol PM. Finally, diffusive passive samplers were used to determine the concentration of nitrogen dioxide (NO2) and BTEX (benzene, toluene, ethylbenzene, and xylenes). To identify possible spatial variations, the studies were conducted at different sites and different heights in the Sanctuary. Particular focus was given to the Easter week during which liturgical services attracting large numbers of people were carried out. Additionally, a comparison with the outdoor values was performed to highlight the accumulation phenomena and other variations in the concentrations of the species. Despite the indoor concentrations of pollutants and variations in the thermohygrometric parameters being generally lower compared to the outdoors (e.g., 5.2–15.0 µg m−3 versus 17.7–45.3 µg m−3 for NO2), the microclimatic conditions were often not in line with the Italian legislation and technical standards.
A Novel Hybridization LC-MS/MS Methodology for Quantification of siRNA in Plasma, CSF and Tissue Samples
Authors: Yuan Long , Dupuis Jean-François , Mekhssian Kevork
Published: February 2023

Therapeutic oligonucleotides, such as antisense oligonucleotide (ASO) and small interfering RNA (siRNA), are a new class of therapeutics rapidly growing in drug discovery and development. A sensitive and reliable method to quantify oligonucleotides in biological samples is critical to study their pharmacokinetic and pharmacodynamic properties. Hybridization LC-MS/MS was recently established as a highly sensitive and specific methodology for the quantification of single-stranded oligonucleotides, e.g., ASOs, in various biological matrices. However, there is no report of this methodology for the bioanalysis of double-stranded oligonucleotides (e.g., siRNA). In this work, we investigated hybridization LC-MS/MS methodology for the quantification of double-stranded oligonucleotides in biological samples using an siRNA compound, siRNA-01, as the test compound. The commonly used DNA capture probe and a new peptide nucleic acid (PNA) probe were compared for the hybridization extraction of siRNA-01 under different conditions. The PNA probe achieved better extraction recovery than the DNA probe, especially for high concentration samples, which may be due to its stronger hybridization affinity. The optimized hybridization method using the PNA probe was successfully qualified for the quantitation of siRNA-01 in monkey plasma, cerebrospinal fluid (CSF), and tissue homogenates over the range of 2.00–1000 ng/mL. This work is the first report of the hybridization LC-MS/MS methodology for the quantification of double-stranded oligonucleotides. The developed methodology will be applied to pharmacokinetic and toxicokinetic studies of siRNA-01. This novel methodology can also be used for the quantitative bioanalysis of other double-stranded oligonucleotides.