bluuebunny/crossref_metadata_2025 huggingface dataset:
Wenhua Juanbi Recipe Attenuates Rheumatoid Arthritis via Inhibiting miRNA‐146a‐Mediated Autophagy
Authors: Zhou Haili , Huang Liuyun , Zhan Kuijun , Liu Xide
Published: November 2022

Background. Wenhua Juanbi Recipe (WJR) is widely used for the treatment of rheumatoid arthritis (RA) in China. However, its mechanism of action remains unclear. This study was designed to investigate the potential therapeutic effects of WJR on the proliferation and apoptosis of synovial fibroblasts in RA and its efficacy in inhibiting miRNA‐146a‐mediated cellular autophagy. Methods. A collagen‐induced arthritis (CIA) Wistar rat model was established. The model rats were administered WJR or methotrexate (MTX) to assess the therapeutic effect of the drugs. The chemical components of WJR were analyzed using UPLC‐Q/TOF‐MS. Histological changes; miRNA‐146a, ATG5, ATG7, ATG12, Beclin1, LC3II, Bax, and Bcl2 expression; synovial apoptosis; and cellular proliferation were assessed. Primary synovial fibroblasts (FLS) were cultured in vitro using tissue block and transfected with miRNA‐146a; an autophagy inducer was added to FLS, inhibiting the PI3K/AKT/mTOR pathway. FLS were cocultured with WJR‐containing serum to observe the effects of miRNA‐146a‐mediated autophagy via the PI3K/AKT/mTOR pathway on CIA‐affected rats. Results. Forty and thirty‐one compounds were identified in WJR in the positive and negative ion modes, respectively. WJR significantly reduced toe swelling, arthritis scores, and expression of miRNA‐146a and autophagy genes (ATG5, ATG7, ATG12, Beclin1, LC32, and Bcl2). Moreover, Bax expression, apoptosis, and attenuated proliferation were observed in rats. WJR could, therefore, regulate autophagy by influencing the miRNA‐146a‐mediated PI3K/AKT/mTOR pathway, which induces apoptosis and proliferation of FLS. Conclusion. WJR can inhibit autophagy, apoptosis, and proliferation in a CIA rat model by inhibiting the miRNA‐146a‐mediated PI3K/AKT/mTOR pathway.
A Study on the Pricing Decision of Remanufacturing Products considering Government Subsidies in a Carbon Trading Environment
Authors: He Zheng , Zhang Tongjing , Yang Xiaohong
Published: November 2022

Considering the characteristics of the carbon trading environment, the impact of government subsidies on pricing decisions of remanufacturing products is studied. First of all, four cases, including those without government subsidies, government subsidies for manufacturers’, government subsidies for retailers’, and centralized decision-making, are analyzed, respectively, and the optimal solutions of new products and remanufacturing products are obtained in four cases. Then, three cases of production subsidies, sales subsidies, and centralized decision-making are compared and analyzed, and the influences of government subsidies on wholesale prices, sales prices, and sales volume are revealed. Finally, the influences of main factors on decision variables and optimal profits are analyzed through numerical simulation, and the main conclusions are verified. The study finds that (1) under two subsidy mechanisms of production subsidies and sales subsidies, the government has the same promoting effect on the sales volume of remanufacturing products; (2) compared with government subsidies to manufacturers or retailers, in the way that manufacturers and retailers make centralized decisions on government subsidies, the sales volume of products increases, and the profits of the entire remanufacturing product supply chain system are optimized.
Penetration of Three Endodontic Sealers in Simulated Lateral Canals during the Lateral Condensation Technique: An In Vitro Study
Authors: El Sayed Mohamed
Published: November 2022

Objective. This study aimed to compare the penetration depths of AH Plus, BioRoot RCS, and GuttaFlow 2 into simulated lateral canals when used with the cold gutta-percha lateral compaction technique. Materials and Methods. Twelve resin training blocks (4 canals perch each resin block) were used. Each primary artificial canal had two lateral canals (apical and coronal). The main canals were instrumented with WaveOne Gold and irrigated with distilled water. The resin blocks were divided into three groups (N = 4 each/16 artificial canals), according to the type of root canal sealer; Group I: AH Plus, Group II: BioRoot RCS, and Group III: GuttaFlow 2. All canals were obturated with the cold lateral condensation technique. The linear extension of each endodontic sealer into the apical and coronal lateral canals was measured using a digital stereomicroscope and measuring software. Data were statistically analyzed using a one-way analysis of variance. The percentages of filling of the lateral canals were calculated and statistically compared using the Mann–Whitney test. Results. The experimental sealers exhibited variable penetration depths into the lateral canals. All sealers showed significantly better penetration ability into the apical lateral canals than the coronal lateral canals (

P
<
0.05

). AH Plus (3.184 ± 0.012 mm/99.5%) and GuttaFlow 2 (3.176 ± 0.017 mm/99.25%) were significantly better than BioRoot RCS (3.096 ± 0.026 mm/96.75%) in filling the apical lateral canals (

P
<
0.05

). BioRoot RCS was the best sealer to fill coronal lateral canals (3.322 ± 0.085 mm/83.05%). Conclusion. During the lateral condensation technique, the filling of the lateral canals is affected by the type of root canal sealer and the location of the lateral canals All the sealers tested have a good ability to fill the apical lateral, while BioRoot RCS was effective in filling both the coronal and apical lateral canals.
Uncommon Surgical Emergencies in the Adult Gynecologic Patient: Two Cases of Missed Diagnosis of Outflow Tract Obstruction from Congenital Uterine Anomalies
Authors: McGuinness Bailey , Llarena Natalia , Falcone Tommaso , Richards Elliott G.
Published: November 2022

Gynecologic emergencies may result from congenital uterine anomalies (CUAs) with outflow tract obstruction. Not limited to the “classic” presentation of an adolescent amenorrheic pain patient, such anomalies should be part of the differential diagnosis for adult female patients presenting with severe pelvic pain. Obstructed rudimentary noncommunicating cavitary horns may result in severe chronic or acute pain and necessitate urgent surgical management. While two-dimensional (2D) ultrasound is often the initial diagnostic tool, three-dimensional (3D) ultrasound and MRI can accurately delineate CUAs for definitive diagnosis. When excision of a rudimentary horn is required, a laparoscopic approach is preferable. This case series focuses on two adult patients with severe pelvic pain due to unicornuate uteruses with obstructed noncommunicating cavitated rudimentary horns. Both cases involve a delayed diagnosis, the inability to make the diagnosis at standard surgical observation, and the resultant need for urgent surgical management.
GABRG2 C588T Polymorphism Is Associated with Idiopathic Generalized Epilepsy but Not with Antiepileptic Drug Resistance in Pakistani Cohort
Authors: Saleem Tayyaba , Maqbool Hafsa , Sheikh Nadeem , Tayyeb Asima , Mukhtar Maryam , Ashfaq Aqsa
Published: November 2022

Idiopathic generalized epilepsy (IGE) is the most prevalent type of epilepsy with genetic origin. Mutations in ion channel genes have been identified as a common cause of IGE. Several studies have reported various epilepsy risk variants of GABRG2 (gamma-aminobutyric acid type A receptor subunit gamma2 subunit) gene in different ethnic groups, but the results are inconsistent. The purpose of this case‐control research is to determine if GABRG2 polymorphisms contribute to IGE susceptibility and antiepileptic drug resistance in Pakistani population. For this purpose, we genotyped exon2, exon5 (C540T and C588T), exon7 (T813C), exon8 (K289M), and exon9 of GABRG2 gene by restriction fragment length polymorphism and Sanger’s sequencing in 87 drug‐responsive idiopathic generalized epilepsy patients, 55 drug‐resistant epilepsy patients, and 83 healthy controls. Restriction fragment length polymorphism (RFLP) and sequencing results indicated only C588T polymorphism in the studied subjects. The comparison of genotypic and allelic frequencies showed significant differences between IGE patients and control groups (P = 0.008 and odds ratio = 4.2) and nonsignificant association of C588T polymorphism in antiseizure medication‐resistant patients (P = 0.9). Our findings showed that C588T polymorphism of GABRG2 is a risk variant for IGE in Pakistani population. Further studies are required to validate the results.
Effect of SiC Addition on Microhardness and Relative Density during Selective Laser Melting of 316L Stainless Steel
Authors: Hadi Raid Mohammed , Taha Ziad Aeyad
Published: November 2022

The utilization of 316L stainless steel has been very common in marine, automotive, architectural, and biomedical applications due to its adequate corrosion resistance to cracks after the completion of welding process. However, there has been ongoing attempts to investigate the potential enhancement in the strength and durability of 316L stainless steel by reinforcing it with silicon carbide (SiC). The present work adopts the selective laser melting (SLM) technique to fabricate SiC-reinforced 316L steel to boost its microhardness and strength properties. The methodology involved the addition of 1% wt. silicon carbide with particle sizes <40 μm to reinforce the stainless steel matrix. An SLM metal printing machine equipped with a continuous wave of 300 W fiber laser is employed to form the specimens. To measure the properties of the final product, EDX, XRD, FESEM, and universal tensile test machines have been used. The maximum value of 296 HV was obtained for a 1% volume of SiC compared to the 285 HV microhardness of pure stainless steel 316L. FESEM examination showed that the SiC microparticles were dissolved completely and they were randomly distributed in the melting basin. The samples were dissolved entirely, and the best porosity was obtained at 0.4% with influential parameters of 200 W laser power, 70 µm hatching distance, 30 µm layer thickness, and 700 mm/s velocities. The results also revealed that the microhardness at these parameters is the best compared to the samples produced with different values. The volumetric energy density was also considered. The findings can be informative to the researchers and manufacturers interested in 316L steel industry.
Total Product and Total Edge Product Cordial Labelings of Dragonfly Graph (Dgn)
Authors: Inayah N. , Erfanian A. , Korivand M.
Published: November 2022

In this paper, we study the total product and total edge product cordial labeling for dragonfly graph Dgn. We also define generalized dragonfly graph and find product cordial and total product cordial labeling for this family of graphs.
Maiden Application of a Modified HBA-Optimized Cascaded (2DOF + FOPIDN)-PD Controller for Load Frequency Control of Diverse Source Power System
Authors: Oladipo Stephen , Sun Yanxia , Wang Zenghui
Published: November 2022

Electricity has become one of the most essential components of establishing a quality standard of living in any country. Consequently, considerable work has been focused on designing a sophisticated load frequency control (LFC) system. However, in light of limited resources and real-world challenges, computationally based control algorithms that are more effective and less expensive remain critically needed. Thus, this paper employs a modified honey badger algorithm (HBA) in conjunction with the concepts of Lévy flight and inertia weight to optimize the parameters of a new cascaded two-degree-of-freedom fractional-PID structure coupled with a proportional derivative (2DOF + FOPIDN)-PD controller to solve LFC problems in an interconnected power system (IPS) comprising conventional and renewable energy sources (RES). The proposed control technique is applied to a two-area IPS under diverse load conditions and in the presence of nonlinear elements and electronic devices. The proposed method is evaluated with respect to a range of performance metrics, such as settling time, undershoots, and error criteria values. The collective performance of the established control scheme indicated that the suggested control approach provides excellent reliability under various load condition scenarios, sensitivity tests, and perturbations, proving the system’s efficacy and dependability.
Edge Intelligence‐Based RAN Architecture for 6G Internet of Things
Authors: Liu Yang , Wang Qingtian , Liu Haitao , Zong Jiaying , Yang Fengyi
Published: November 2022

Edge Intelligence, which blends Artificial Intelligence (AI) with Radio Access Network (RAN) and edge computing, is recommended as a crucial enabling technology for 6G to accommodate intelligent and efficient applications. In this study, we proposed Edge Intelligent Radio Access Network Architecture (EIRA) by introducing new intelligence modules, which include broadband edge platforms that allow policies to interact with virtualized RAN for various applications. We also developed a Markov chain‐based RAN Intelligence Control (RIC) scheduling policy for allocating intelligence elements. Experimental results justified that the virtualized RAN delivers on its performance promises in terms of throughput, latency, and resource utilization.
Cytotoxic Evaluation of the New Composite Resin through an Artificial Pulp Chamber
Authors: Marigo Luca , Triestino Alessio , Castagnola Raffaella , Vincenzoni Federica , Cordaro Massimo , Di Stasio Enrico , Mordente Alvaro , Nocca Giuseppina
Published: November 2022

The aim of this study was to analyse the cytocompatibility of Surefil One (SuO) with respect to the release of monomers from the material. The following reference materials were chosen: SDR Flow Plus (SDR, Dentsply Sirona, Konstanz, Germany), One Q Bond (Q, Dentalica, Milan, Italy), and Ketac (K, 3M‐ESPE, USA). Fifteen dentin discs (2 mm thickness and diameter) were obtained from 15 third molars and were used in this study. After dentin disc permeability measurement, murine fibroblasts were grown, and the pulp surface of the dentinal disc was placed in direct contact with the cells immersed in DMEM. The experimental materials were positioned on the occlusal side of each dentinal disc until a uniform thickness of 2 mm was obtained. Then, the discs were inserted into an artificial pulp chamber for 24 hours to assess the cytocompatibility. Afterwards, the moles of monomers leached from the specimens in DMEM were determined using HPLC. Statistical analysis was performed using ANOVA (p < 0.05). Under the experimental conditions, the toxic effect induced by all tested materials was slight or absent. Diurethane dimethacrylate and acrylic acid were not found in the culture media. It is concluded that all materials have good cytocompatibility consistent with the nondeterminability of the monomers released after polymerization.
Topological Indices of Novel Drugs Used in Autoimmune Disease Vitiligo Treatment and Its QSPR Modeling
Authors: Parveen Saima , Awan Nadeem Ul Hassan , Farooq Fozia Bashir , Fanja Rakotondrajao , Anjum Qurat ul Ain
Published: November 2022

A topological index is a real number derived from the structure of a chemical graph. It is helpful to determine the physicochemical and biological properties of a wide range of drugs, and it better reflects the theoretical properties of organic compounds. This is accomplished using degree‐based topological indices. Vitiligo is a common, acquired skin pigmentation disorder that significantly impacts the quality of life. It frequently embodies a therapeutic challenge, resulting in interest in alternative treatments based on vitamin and herbal supplements. In this article, azathioprine, clobetasol, desonide, hydrocortisone valerate, and other drugs utilized to cure vitiligo have discoursed, and the goal of QSPR revision is to determine the mathematical relationship between properties under investigation (e.g., polarity and enthalpy) and diverse descriptors associated with the drugs’ molecule. The QSPR model will help to predict physical properties. In this study, topological indices (TIs) imposed on said drugs were found to have a good correlation with physicochemical properties in this course. Finally, this work can be helpful to design and synthesize new vitiligo treatments and other disease drugs.
Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in Nondiabetic Populations
Authors: Xu Dan , Nair Ankith , Sigston Charlie , Ho Chau , Li Jia , Yang Daya , Liao Xinxue , Chen Wei , Kuang Ming , Li Yanbing , Reid Christopher , Xiao Haipeng
Published: November 2022

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been observed in several large cardiovascular outcome trials to significantly reduce the incidence of major cardiovascular event (MACE) with type 2 diabetic patients. The clinical trials of GLP-1 RAs, including lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, and dulaglutide, are associated with a significantly 14% lower risk of MACE in patients with T2DM and a history of CV disease, and with a nonsignificantly 6% lower risk in patients without history of CV disease. Some of the interpretation with GLP-1 RA trials suggested the possible role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in primary prevention of cardiovascular diseases in nondiabetic individual, echoed by a recent editorial redefining the role of GLP-1 RAs being beyond glycaemic control. The narrative review provides an in-depth insight into GLP-1 RA use guideline in different countries and regions of the world and examines the safety and concern of GLP-1 RA use. The narrative review draws the comparison of GLP-1 RA use between diabetic and nondiabetic individual in terms of cardiovascular and metabolic benefits and points out the direction of future clinical trials of GLP-1 RAs in nondiabetic individuals. The focus of the review is on GLP-1 RAs’ preventive roles in nondiabetic individuals with cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome (PCOS), and perioperative complications of bariatric surgery, albeit in small studies and subset analysis of clinical trials of diabetic patients.
Influence of High-Frequency Repetitive Transcranial Magnetic Stimulation on Neurobehavioral and Electrophysiology in Patients with Disorders of Consciousness
Authors: Chen Jian-Min , Chen Qing-Fa , Wang Zhi-Yong , Chen Yang-Jia , Zhang Nan-Nan , Xu Jian-Wen , Ni Jun
Published: November 2022

Objective. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DOC). However, its therapeutic effects in the literature are inconsistently documented. The primary aim of this study was to explore the alterations in neural connectivity and neurobehavioral reactivity during rTMS modulation in patients with DOC. In addition, safety was investigated as a secondary aim. Methods. The presence of bilateral N20 components in DOC patients was determined by somatosensory-evoked potential (SEP) before enrollment in the study. A total of 64 patients were enrolled and randomly placed into the active and sham groups. Ultimately, 50 patients completed the study. Twenty-five patients in the active group underwent real HF-rTMS, and 25 patients in the sham group underwent sham HF-rTMS, which was delivered over the left dorsolateral prefrontal cortex (DLPFC). The outcome measures of performed pre- and postintervention included the latencies of the N20 and N20-P25 amplitudes of SEP, brainstem auditory-evoked potential (BAEP) grade, JFK Coma Recovery Scale-Revised (CRS-R) score, and Glasgow Coma Scale (GCS) score; any adverse events were recorded at any time during the intervention. Result. Following six weeks of treatment, a significant increase was observed in the total CRS-R and GCS scores, and the N20-P25 amplitudes of patients in the two groups were compared with that obtained from preintervention (all

p

values < 0.05). The waves of BAEP in the two groups also showed a trend toward normalized activity compared with preintervention grades (

p

values < 0.05). A significant decrease in the latencies of N20 (

p

values < 0.001) was observed in the active group compared with measurements obtained from preintervention, whereas no significant decrease was observed in the sham group (

p

values = 0.013). The improvement in total CRS-R scores (

p

values = 0.002), total GCS scores (

p

values = 0.023), and N20-P25 amplitudes (

p

values = 0.011) as well as the decrease in latencies of N20 (

p

values = 0.018) and change in BAEP grades (

p

values = 0.013) were significantly different between the two groups. The parameters in neural connectivity (N20-P25 amplitudes, N20 latencies, and BAEP grades) were significantly correlated with the total CRS-R and GCS scores at postintervention, and the changes of CRS-R before and after interventions have a positive relationship with N20-P25 amplitudes. No adverse events related to the rTMS protocol were recorded. Conclusion. Neural connectivity levels are affected by HF-rTMS and are significantly related to clinical responses in DOC patients with the presence of bilateral N20. The elevation of neural connectivity levels may lay a foundation for successful HF-rTMS treatment for DOC patients.
HPV-Related Prognostic Signature Predicts Survival in Head and Neck Squamous Cell Carcinoma
Authors: Zhao Hongyu , Wang Fengxu , Wang Xuehai , Zhao Xinyuan , Ji Jinfeng
Published: November 2022

Background. Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, worldwide. Considering the role of human papilloma virus (HPV) in tumor development and sensitivity to treatment of HNSCC, we aimed to explore the prognostic classification ability of HPV-related signatures in head and neck cancer. Methods. HPV-related signatures were screened out based on Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. HPV-related signatures with prognostic value were identified through univariate Cox regression analysis and a risk signature was established by least absolute shrinkage and selection operator (LASSO). Further, we developed a nomogram by integrating independent prognostic factors. Results. A total of 55 HPV-associated signatures were differentially expressed and ten of them were associated with prognosis of HNSCC patients. The prognostic signature based on CDKN2A, CELSR3, DMRTA2, SERPINE1, TJP3, FADD, and IGF2BP2 expression was constructed. Univariate and multivariate regression analyses demonstrated that the novel prognostic signature was an independent prognostic factor of HNSCC. The nomogram integrating the prognostic signature and other independent prognostic factors was developed. Conclusion. In summary, the prognostic signature of the HPV-related signatures might serve as an important prognostic biomarker for patients with HNSCC.
Virological Changes of Chronic Hepatitis B Patients with Minimally Elevated Levels of Alanine Aminotransferase: A Meta-Analysis and Systematic Review
Authors: Chen Xiyao , Zheng Xingrong , Wu Hewei , Zhang Boxiang , Peng Liang , Xie Chan
Published: November 2022

Background. Chronic hepatitis B (CHB) patients with normal or minimally increased levels of alanine aminotransferase (ALT) are still at the risk of hepatocellular carcinoma, cirrhotic events, and mortality. However, there is a debate over the initiation of antiviral treatment for these patients. This systematic review and mate-analysis aimed to explore this problem. Methods. MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were systematically searched for retrieving relevant studies with risk ratios (RRs) or risk differences (RDs) for virological changes between antivirus-treated and no antivirus-treated CHB patients with ALT levels less than two-fold of the upper limit of normal. Retrieved data ranged from January 1990 to October 2020. Results. Of 6783 abstracts screened, 9 studies met the criteria for inclusion in the systematic review and had a low risk of bias. Among studies that were involved in the meta-analyses, it was found that the rates of HBsAg loss (RR = 12.22, 95% confidence interval (CI): 4.28–34.95,

P
<
0.001

), HBsAg seroconversion (RR = 19.90, 95% CI: 2.75–144.09,

P
=
0.003

), and undetectable HBV DNA (RR = 11.89, 95% CI: 2.44–57.89,

P
=
0.002

) were both higher in the antiviral treatment group compared with placebo or no treatment group. Subgroup analysis suggested that patients who received interferon (IFN)-based therapy were more inclined to achieve HBsAg loss (

P
=
0.010

), HBsAg seroconversion (

P
=
0.020

), and HBeAg loss (

P
=
0.002

). Conclusion. From a sizable population, it was revealed that CHB patients with normal or minimally increased levels of ALT could benefit from the antiviral therapy, especially those who received IFN-based treatment.
Study on Vehicle Load Model of Baijianhe Bridge
Authors: Yang Zeying , Sun Yinglin , Qu Jianbo , Wang Chenghe , Wang Tianmin
Published: November 2022

In order to calculate the vehicle load model of Baijianhe Bridge, based on the vehicle load data of the health monitoring system, the vehicle type, vehicle weight, wheelbase, and other information were counted and the data were processed and diagraphed to obtain the probability density distribution. At the same time, the automobile load model parameters relative to the national current code and finite element method are calculated. The results show that 2‐axle and 6‐axle vehicles are the main vehicle types, accounting for about 48%. The number of upstream and downstream vehicles is the same, but the number of vehicles in the lane is much higher than in the overtaking lane. The carriageway is dominated by 6‐axle vehicles, while the overtaking lane is dominated by 2‐axle vehicles. The probability density distribution of vehicle weight in overtaking lane obeys mixed Gaussian distribution and that in the carriageway obeys Weibull distribution. According to the measured vehicle load data, the vehicle load suitable for Baijianhe Bridge is 1.1 times the highway‐I vehicle load of the current Chinese standard “General Code for Design of Highway Bridges and Culvers” (JTG D60‐2015).
Hybridization of Aminoadamantanes with Cinnamic Acid Analogues and Elucidation of Their Antioxidant Profile
Authors: Chochkova Maya , Georgieva Almira , Ilieva Tsvetelina , Andreeva Madlena , Pramatarov Georgi , Petek Nejc , Petrova Petranka , Štícha Martin , Mitrev Yavor , Svete Jurij
Published: November 2022

A series of seventeen cinnamic acid hybrids (4ai–ci) were obtained through an amidation of aminoadamantanes (amantadine, rimantadine, and memantine) with mixed anhydride generated from different substituted cinnamic acid and ethyl chloroformate. 1H NMR, 13C NMR, IR, and HRMS were used for the confirmation of the structures of the synthesized hybrids. Moreover, the antioxidant profiles of amides were estimated as per five different in vitro methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid cation radical (ABTS⁺), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC) assay, and inhibition of Fe(III)/asc induced lipid peroxidation (LP) in brain homogenate. For comparison, caffeic acid (CaffA), known as a potent naturally occurring antioxidant, was used as a reference compound in our study. The results revealed that the most prominent antioxidant activity was demonstrated by compound 4b2, with excellent CUPRAC, FRAP, scavenging ABTS+˙ potential, and inhibition of Fe/asc–induced LP, followed by 4c6 > 4a6 > CaffA > 4c5 and 4a5 > 4a7. Overall, the results suggest that the hybrids (4b2, 4c6, and 4a6) consisting of a caffeoyl moiety and lipophilic adamantane core endow the molecules with the higher antioxidant activity than their parent compound (caffeic acid), especially against LP. Thus, these promising antioxidants could have beneficial effects in various pathological conditions, where oxidative stress is implicated.
An Ultrafast Fluorescent Probe for the Detection of Peroxynitrite in Living Cells
Authors: Wang Xiaofeng , Xiao Shu , Zhou Xuejun , Duan Tingting
Published: November 2022

Peroxynitrite (ONOO−), a highly reactive nitrogen species, which plays a crucial role in numerous physiological and pathological processes of cell functionalization. The anomalous concentration of ONOO− may result in a range of diseases, such as arthritis, neurological disorders, and even cancer. Therefore, it is urgent to develop a simple and effective tool to monitor the fluctuation of ONOO− levels in biological systems. Herein, an ultrafast fluorescent probe (HND-ONOO) is proposed to detect ONOO−, which displays brilliant fluorescence in less than 30 s with a large Stokes shift. Furthermore, the probe exhibited the lower detection limit (48 nM) and satisfactory results in differentiating ONOO− from other related species. The probe that possesses good biocompatibility and low toxicity was employed to monitor the level of exogenous and endogenous ONOO− in living cells. Thus, the probe HND-ONOO could be served as a potential imaging tool to visualize intracellular ONOO− and understand the relationship between ONOO− and inflammation.
Targeting MLL Methyltransferases Enhances the Antitumor Effects of PI3K Inhibition in Hormone Receptor–positive Breast Cancer
Authors: Jones Robert B. , Farhi Jonathan , Adams Miranda , Parwani Kiran K. , Cooper Garrett W. , Zecevic Milica , Lee Richard S. , Hong Andrew L. , Spangle Jennifer M.
Published: November 2022

The high frequency of aberrant PI3K pathway activation in hormone receptor–positive (HR+) breast cancer has led to the development, clinical testing, and approval of the p110α-selective PI3K inhibitor alpelisib. The limited clinical efficacy of alpelisib and other PI3K inhibitors is partially attributed to the functional antagonism between PI3K and estrogen receptor (ER) signaling, which is mitigated via combined PI3K inhibition and endocrine therapy. We and others have previously demonstrated chromatin-associated mechanisms by which PI3K supports cancer development and antagonizes ER signaling through the modulation of the H3K4 methylation axis, inhibition of KDM5A promoter H3K4 demethylation and KMT2D/MLL4-directed enhancer H3K4 methylation. Here we show that inhibition of the H3K4 histone methyltransferase MLL1 in combination with PI3K inhibition impairs HR+ breast cancer clonogenicity and cell proliferation. While combined PI3K/MLL1 inhibition reduces PI3K/AKT signaling and H3K4 methylation, MLL1 inhibition increases PI3K/AKT signaling through the dysregulation of gene expression associated with AKT activation. These data reveal a feedback loop between MLL1 and AKT whereby MLL1 inhibition reactivates AKT. We show that combined PI3K and MLL1 inhibition synergizes to cause cell death in in vitro and in vivo models of HR+ breast cancer, which is enhanced by the additional genetic ablation of the H3K4 methyltransferase and AKT target KMT2D/MLL4. Together, our data provide evidence of a feedback mechanism connecting histone methylation with AKT and may support the preclinical development and testing of pan-MLL inhibitors.

Significance:

Here the authors leverage PI3K/AKT-driven chromatin modification to identify histone methyltransferases as a therapeutic target. Dual PI3K and MLL inhibition synergize to reduce clonogenicity and cell proliferation, and promote in vivo tumor regression. These findings suggest patients with PIK3CA-mutant, HR+ breast cancer may derive clinical benefit from combined PI3K/MLL inhibition.
Does Clearance of Vulvar Lichen Sclerosus after a Corticosteroid Treatment Correspond to a Decrease in Disease-Related Burden? Results from a Cohort Study Using Pictorial Representation of Illness and Self-Measure and the Dermatology Life Quality Index
Authors: Borghi Alessandro , Flacco Maria Elena , Zedde Pierantonia , Toni Giulia , Schettini Natale , Corazza Monica
Published: November 2022

Background and Objectives: Complete clearance of vulvar lichen sclerosus (VLS) occurs in a minority of treated patients. Disease persistence may impact patient well-being. The main objective of this study was to assess if achieving a complete clearance with a corticosteroid treatment leads to a benefit in terms of patient suffering and quality-of-life (QoL) impairment. Methods: We performed an observational study on a cohort of VLS women, who applied mometasone furoate 0.1% ointment for 12 weeks. At treatment completion (T1), we compared the patients who achieved clearance in symptoms (Global Subjective Score [GSS] = 0) or in objective features (Global Objective Score [GOS] = 0) or in both with those who achieved a lower degree of improvement, on the basis of Pictorial Representation of Illness and Self-Measure (PRISM) and Dermatology Life Quality Index (DLQI) scores. Results: In the whole sample (n = 101), GSS, GOS, PRISM, and DLQI scores significantly improved after treatment from baseline; 34 patients (35.8%) achieved GSS = 0, 26 (25.7%) achieved GOS = 0, and 11 (11.5%) clearance of GSS and GOS. PRISM scores at T1 were significantly higher in patients who achieved clearance of symptoms when compared with those who did not, including patients achieving 50–99% GSS improvement from baseline. DLQI scores were lower in patients who achieved clearance of symptoms, signs, or both when compared with the others. Conclusions: VLS clearance corresponded to a significant improvement in the QoL of VLS patients, also in comparison with those who achieved a substantial but incomplete decrease of symptom and sign scores, and should become an ideal therapeutic goal.
Porcine Endogenous Retrovirus Induces CXCL10 in Human Monocytes and Monocyte-Derived Primary Cells
Authors: Al-Shehabi Hussein , Bannert Norbert
Published: November 2022

Introduction: Pigs are suitable donor species for xenotransplantation and biological materials from these animals are used for this purpose for many years. A major risk of xenotransplantation is a zoonosis by transspecies transmission of animal viruses. In this regard, porcine endogenous retroviruses (PERVs) are of paramount importance because some of them are able to infect human cells and could induce innate immune responses. Methods: Using a replication-competent polytropic PERV-A/C strain, we have analysed the induction of innate immune responses by this virus in human monocytes, monocyte-derived macrophages, and monocyte-derived dendritic cells. Results: PERV-A/C elevates the expression of the C-X-C motif chemokine 10 (CXCL10) up to 1,000-fold in human monocytes and monocyte-derived primary cells. In comparison to CXCL10, the levels of interferon-β (IFN-β) and interferon-stimulated gene 54 (ISG54) were almost unchanged. Heat-inactivated virus did not induce CXCL10 expression. Neither treatment with the reverse transcriptase inhibitors azidothymidine (AZT) and stavudine (d4T) nor treatment with the integrase inhibitor raltegravir (RAL) reduced the activation levels. Furthermore, depletion of SAM domain and HD domain-containing protein 1 (SAMHD1), a restriction factor that blocks PERV-A/C infection at the level of reverse transcription in these myeloid cells, had no significant effect on the CXCL10 induction level. These results imply that innate immune sensing leading to the strong CXCL10 response occurs at an early step of the replication process and does not require products of reverse transcription. Inhibition of Janus kinases (JAKs) by AT9283 prevented the observed CXCL10 induction by the virus, providing evidence that the JAK-STAT signalling pathway is involved in the CXCL10 response in theses myeloid cells. Conclusion: Our findings highlight PERVs as inducers of the pro-inflammatory chemokine CXCL10 and other innate immune responses in human monocytes and derived cells with potential implications in the context of xenotransplantation.
Association between Level of Parental Oral Health Literacy and the Rational Use of Fluoride for Children from 0 to 4 Years of Age after Instruction: An Intervention Trial
Authors: Lisboa Sara Oliveira , Assunção Cristiane Meira , Drumond Clarissa Lopes , Serra-Negra Júnia Maria Cheib , Machado Márcia Gomes Penido , Paiva Saul Martins , Ferreira Fernanda de Morais
Published: November 2022

An inadequate level of oral health literacy (OHL) can hinder the understanding of dental information, which can have a negative impact on health promotion actions, such as the rational use of fluoride. The aims of the present study were (1) to look for association between parents/guardians’ OHL and the amount of fluoride toothpaste used for children from zero to four years of age; (2) to compare the effect of different modes of educational interventions on the amount of fluoride toothpaste used for children from zero to four years of age; and (3) to assess the ability of parents/guardians to choose a toothpaste with adequate fluoride concentration, after the educational intervention. A randomized intervention study was conducted with parents/guardians of children from zero to four years of age (n = 145). The participants answered the Oral Health Literacy Adults Questionnaire and a questionnaire addressing sociodemographic characteristics. The participants were allocated to four intervention groups based on type of counseling (written, oral, written + photograph, and oral + photograph), with randomization stratified by level of OHL. The participants were instructed to place the adequate amount of toothpaste on a toothbrush for children from zero to four years of age (smear of 0.125 mg) before and after the intervention. The correct choice of toothpaste was also evaluated by the interpretation of the labels of four toothpastes of different brands and with different concentrations of fluoride. Associations between variables were tested using the Student’s t test and one-way ANOVA. Level of OHL was associated with the amount of fluoride toothpaste deposited prior to the educational intervention (p = 0.021) and the percentage of approximation to the appropriate amount of fluoride toothpaste (p < 0.05). The choice of toothpaste was associated with schooling (p = 0.031). In conclusion, parents/guardians with adequate OHL better quantified fluoride toothpaste before and after the educational intervention and also came closer to the appropriate amount of toothpaste after the educational intervention. No significant differences in the final amount of toothpaste placed on the toothbrush were found among the intervention groups. The choice of the correct toothpaste was associated with a higher level of schooling.
The effect of iron coating on stabilizing rice direct seeding onto puddled soil on growth and production
Authors: Ramli Ramli , Kaimudddin Kaimudddin , Riadi Muh , Rasyid Burhanuddi
Published: November 2022

Rice is a food-crop commodity that plays an important role in Indonesia's economy. This research aims to analyze the following aspects: 1) the response of several rice varieties to the growth and production of rice and 2) the effect of iron coating on the growth and production of rice. This study was conducted in Borongloe Village, Bontomarannu District, Gowa Regency, from March to December 2021. The split-plot design was applied for two factors. The main plot was used to test for the first factor, namely variety, for Inpari 32, Cigeulis, and Mekongga, and the subplot was used to test for the second factor, namely coating, uncoating, 25% coating, and 50% coating. The two factors were combined to create 9 treatment combinations. Each treatment combination was repeated four times. The Inpari 32 variety was found to be the best variety for coating based on the number of pithy seeds (82.04 per panicle), the weight of the seeds per panicle (2.50 g), and production (4.04 t h-1). Significant plant height was also seen in the Mekongga variety (121.39 cm). Furthermore, the 25% coating treatment was the best treatment for increasing crop yields based on the character of the number of tillers (24.32 tillers per clump) and the number of productive tillers (19.31 stem).
Um giro por epistemologias afro-ameríndias e inclusivas: relato e experiência do Curso de Teatro da Unifap
Authors: Carvalho Adélia Aparecida da Silva , Paula Emerson de
Published: November 2022

Este artigo apresenta um relato sobre a importância de fomentar a discussão e a reflexão sobre epistemologias de inclusão e de recorte afroameríndio nos cursos de teatro, em específico na Licenciatura em Teatro da Universidade Federal do Amapá (Unifap). Contextualiza-se o processo de expansão da formação em Artes Cênicas pelo Brasil, com ênfase na Região Norte.
Teatro Copacabana: o comércio elegante na cena de Henriette Morineau
Authors: Schenker Daniel
Published: November 2022

O artigo procura situar a companhia Os Artistas Unidos dentro do processo de transição rumo ao teatro brasileiro moderno e destacar o perfil artístico estabelecido por ela no Teatro Copacabana durante os anos que permaneceu instalada por lá. Há também a intenção de fornecer um breve contexto da movimentação teatral no Rio de Janeiro na metade do século XX com o surgimento em grande escala de salas de espetáculos na Zona Sul da cidade, sem, porém, ameaçar a força da região central. Esse panorama é traçado por meio de textos de pesquisadores da história do teatro brasileiro e por registros de depoimentos de artistas que trabalharam ao longo do período referido.
Um olhar para o circo, o teatro e os espetáculos de variedades guiado pela pena de Machado de Assis
Authors: Lopes Daniel de Carvalho , Silva Erminia
Published: November 2022

Adotando como referencial as críticas teatrais, crônicas e demais produções literárias do escritor Machado de Assis, pretendemos por meio deste artigo apresentar um olhar para as apresentações circenses, teatrais e de variedades do Rio de Janeiro na segunda metade do século XIX. Guiados por seus escritos, podemos entrar em contato com suas posturas críticas e preferências quanto às ofertas artísticas do período e compreender, em certa medida, a profusão de exibições circenses e de variedades na cidade, a concorrência que ofereciam às produções teatrais e mesmo os discursos contrários aos espetáculos de circo proferidos tanto por Machado de Assis quanto por outros autores do período. Assim, as crônicas e críticas machadianas abordam interessante panorama do cenário da dramaturgia, das exibições circenses e de atrações variadas da época, favorecendo a compreensão do funcionamento da cena artística e dos divertimentos nacionais na segunda metade do século XIX.
From Anti-Government to Anti-Science: Why Conservatives Have Turned Against Science
Authors: Oreskes Naomi , Conway Erik M.
Published: November 2022

Empirical data do not support the conclusion of a crisis of public trust in science. They do support the conclusion of a crisis of conservative trust in science: polls show that American attitudes toward science are highly polarized along political lines. In this essay, we argue that conservative hostility toward science is rooted in conservative hostility toward government regulation of the marketplace, which has morphed in recent decades into conservative hostility to government, tout court. This distrust was cultivated by conservative business leaders for nearly a century, but took strong hold during the Reagan administration, largely in response to scientific evidence of environmental crises that invited governmental response. Thus, science-particularly environmental and public health science-became the target of conservative anti-regulatory attitudes. We argue that contemporary distrust of science is mostly collateral damage, a spillover from carefully orchestrated conservative distrust of government.
What Does “Trust in the Media” Mean?
Authors: Schudson Michael
Published: November 2022

Is public trust in the news media in decline? So polls seem to indicate. But the decline goes back to the early 1970s, and it may be that “trust” in the media at that point was too high for the good of a journalism trying to serve democracy. And “the media” is a very recent (1970s) notion popularized by some because it sounded more abstract and distant than a familiar term like “the press.” It may even be that people answering a pollster are not trying to report accurately their level of trust but are acting politically to align themselves with their favored party's perceived critique of the media. This essay tries to reach a deeper understanding of what gives rise to faith or skepticism in various cultural authorities, including journalism.
Specific Sources of Trust in Generals: Individual-Level Trust in the
U.S. Military
Authors: Margulies Max , Blankshain Jessica
Published: November 2022

This essay explores the individual-level determinants of trust in the U.S. military. Prior research has identified five possible drivers of societal trust in the military: performance, professionalism, persuasion, personal connection, and partisanship. Using data from the American National Election Studies and the General Social Survey, we emphasize the importance of understanding trust at an individual level, as perceptions of military performance and professionalism are not objective but mediated by individual-level factors. Our findings reinforce mixed support for trust being linked to assessments of military success on or off the battlefield, and undermine arguments that relate high trust to a widening gap between the military and civilian society. We also present new evidence for generational and ideational sources of military trust consistent with recent speculation that trust in the military is declining. Overall, we show that individual-level trust may be difficult to change, but that public trust in the military has consequences for a variety of defense-oriented policies.
Parenthetical conditionals and insubordinate clauses in Ancient Greek
Authors: Ruiz Yamuza Emilia
Published: November 2022

The purpose of the article is an in-depth study of the pragmatic and textual functions of several conditional clauses of ancient Greek constructed with verbs meaning “to want”. As a prior step, six types of structures are identified applying Thetical Grammar concepts and the idea of insubordination: five of these are parenthetical, and one is insubordinate. The structures work in the domain of speaker/hearer interaction, the domain of text organisation—reformulators and exemplifiers—and the domain of expressing the speaker’s attitudes.
Legal Certainty and Stability in the Face of Sea Level Rise: Trends in the Development of State Practice and International Law Scholarship on Maritime Limits and Boundaries
Authors: Vidas Davor , Freestone David
Published: November 2022

This article identifies and documents a trend in State practice over the past decade or so, regarding the impact of sea level rise on the lawfully determined limits of maritime zones and the existing maritime boundaries. It juxtaposes this development with the findings and recommendations of two committees of the International Law Association in 2012 and 2018 – the Committees on Baselines and Sea Level Rise – and examines the role played since 2019 by the International Law Commission. It explores the implications of emerging State practice for the interpretation of the rules and principles of the 1982 UN Law of the Sea Convention. It documents the complex interactions between the findings of international law scholarship and the evolution of State practice, and concludes that this interaction has played an important role in facilitating legal certainty and stability in the development of a response to this increasingly pressing international law issue.