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To achieve high precision, stability, and good surface quality when producing micro-dimple arrays on cylindrical surfaces, we propose a new processing method known as radial ultrasonic rolling electrochemical micromachining (RUREMM) in this study. This method is based on the electrochemical micromachining (EMM) and ultrasonic machining principle. The relevant simulation model was created, and ANSYS researched the flow field characteristics of the electrolyte between the array electrodes and the workpiece. Micro-dimple arrays were created on a SS304 cylindrical surface with the consideration of the effects of the machining parameters, including ultrasonic amplitude and applied pulse voltage. Compared with the EMM, the average width of the micro-dimples is reduced by 24.5%, the aspect ratio of the dimple is increased by 108.0%, and the surface roughness of micro-dimples is decreased by 59.7%. In addition, the localization and the surface quality of micro-dimples by RUREMM can be improved when using appropriate machining parameters.

The goal of this study was to identify genes that were differentially methylated and differentially expressed and their related signaling pathways in ovarian endometriosis tissue. First, the DNA methylation and gene expression profiles in the endometrial tissue of patients with ovarian endometriosis were studied using Illumina 450K methylation microarray analysis and the GSE141549 gene expression dataset. Second, differentially methylated and differentially expressed genes, herein referred to as differentially methylated/expressed genes, were identified and protein-protein interaction networks and functional analysis of these genes were determined. Third, qPCR and immunohistochemistry of patient samples was used to confirm the differential expression of a subset of differentially methylated/expressed genes. Finally, the GSE7305 dataset was used confirm the expression profile of differentially methylated/expressed genes and to determine the potential usefulness of these genes for diagnosis of endometriosis. A total of 37 hypermethylated low-expression genes and 66 hypomethylated high-expression genes were identified in ovarian endometriosis patients. Protein-protein interaction and functional analysis highlighted 8 hypermethylated low-expression genes (KRT19, KRT8, ESR1, PRL, SFN, IL20RA, IL2RB, and PAX8) and 4 hypomethylated high-expression genes (CYP11A1, NR5A1, ME1, and GSTM1). Significantly, both of these gene sets had a diagnostic value for patients with ovarian endometriosis. Signaling pathways that were identified included JAK-STAT (involving IL20RA and IL2RB), prolactin (involving PRL and ESR1), Staphylococcus aureus infection (involving KRT19), viral protein interaction with cytokine and cytokine receptor (involving IL20RA and IL2RB), cytokine-cytokine receptor interaction (involving IL20RA and IL2RB), and drug metabolism-cytochrome P450 (involving GSTM1). The differentially methylated/expressed genes and enriched signaling pathways identified in this study are likely to be associated with the process of ovarian endometriosis.

The objective of the study was to find the most effective retracting method for the six maxillary anterior teeth with double-slot lingual brackets using a lever arm and miniscrew system.Six finite element models were constructed: (A) a ribbon-wise archwire with a lever arm; (B) a ribbon-wise archwire with a lever arm and a sectional edgewise archwire; (C) a ribbon-wise archwire and a sectional edgewise archwire with a lever arm; (D) an edgewise archwire with a lever arm; (E) an edgewise archwire with a lever arm and a sectional ribbon-wise archwire; and (F) an edgewise archwire and a sectional ribbon-wise archwire with a lever arm. Initial displacements of maxillary teeth driven by a 1.5 N retraction force to the lever arm were analysed.In models B, C, E and F, anterior torque loss and inter-canine distance increases were significantly lower than that of the models without auxiliary archwires. In models C and F, the main archwire was less likely deformed. In models A, B and C, the displacement of canines in sagittal and vertical directions were less than in models D, E and F.The combination of edgewise and ribbon-wise archwires in double-slot lingual brackets effectively preserves the anterior arch shape. An edgewise archwire with lever arms on the auxiliary sectional ribbon-wise archwire is recommended for better performance in anterior teeth retraction.

The first enantioselective total synthesis of cerorubenic acid-III is described in detail. Different strategies and attempts, based on a type II [5+2] cycloaddition reaction, leading to the bicyclo[4.4.1] ring system with a strained bridgehead double bond, are depicted. Furthermore, sodium naphthalenide was found to be efficient in the chemoselective reduction of 8-oxabicyclo[3.2.1]octene, with three transformations completed in one operation. An unusual SN1 transannular cyclization reaction was applied to construct the synthetically challenging vinylcyclopropane moiety. This strategy enabled the total synthesis of cerorubenic acid-III in 19 steps.

Background: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. Methods: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients’ endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). Results: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02–1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01–2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. Conclusion: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

Objective To explore the effects of two functional genetic variants of poly(ADP-ribose) polymerase-1 (PARP-1) on the susceptibility to epithelial ovarian cancer (EOC), the platinum-based chemotherapeutic response, and the prognosis of northern Chinese patients. Study Design This case-control study included 710 EOC patients in the case group and 700 healthy women in the control group. Two polymorphisms (rs1136410 and rs8679) of PARP-1 were genotyped by polymerase chain reaction and ligase detection reaction. Results The genotype frequencies of rs1136410 and rs8679 were not significantly different between the case and control groups. However, the CC genotype of rs1136410 was significantly associated with a favorable response to platinum drugs. Compared with the TT genotype, the CC genotype of rs1136410 was related to a reduced risk of platinum resistance (adjusted OR: 0.40; 95% CI = 0.24-0.67; P = 0.001). In addition, multivariable analysis containing clinical variables showed that patients who carried the rs1136410 CC genotype had a significantly improved progression-free survival compared with patients who carried the TT genotype (HR = 0.67, 95% CI = 0.47-0.97, P = 0.031). Conclusion The rs1136410 polymorphism may serve as a potential marker for predicting the response to platinum agents and prognosis of EOC patients treated with surgery and platinum-based chemotherapy.

The objective of this study was to investigate the optimal range of rotational moment for the mandibular lateral incisor, canine and first premolar to determine tooth movements during orthodontic treatment using hydrostatic stress and logarithmic strain on the periodontal ligament (PDL) as indicators by numerical simulations. Teeth, PDL and alveolar bone numerical models were constructed as analytical objects based on computed tomography (CT) images. Teeth were assumed to be rigid bodies, and rotational moments ranging from 1.0 to 4.0 Nmm were exerted on the crowns. PDL was defined as a hyperelastic–viscoelastic material with a uniform thickness of 0.25 mm. The alveolar bone model was constructed using a non-uniform material with varied mechanical properties determined based on Hounsfield unit (HU) values calculated using CT images, and its bottom was fixed completely. The optimal range values of PDL compressive and tensile stress were set as 0.47–12.8 and 18.8–51.2 kPa, respectively, whereas that of PDL logarithmic strain was set as 0.15–0.3%. The rotational tendency of PDL was around the long axis of teeth when loaded. The optimal range values of rotational moment for the mandibular lateral incisor, canine and first premolar were 2.2–2.3, 3.0–3.1 and 2.8–2.9 Nmm, respectively, referring to the biomechanical responses of loaded PDL. Primarily, the optimal range of rotational moment was quadratically dependent on the area of PDL internal surface (i.e. area of PDL internal surface was used to indicate PDL size), as described by the fitting formula. Biomechanical responses of PDL can be used to estimate the optimal range of rotational moment for teeth. These rotational moments were not consistent for all teeth, as demonstrated by numerical simulations. The quantitative relationship between the area of PDL internal surface and the optimal orthodontic moment can help orthodontists to determine a more reasonable moment and further optimise clinical treatment.

Summary Natural products with a bridgehead double bond, such as taxol and CP molecules, have long attracted considerable attention from chemists because of their promising bioactivity and structural complexity, with the high ring-strain energy in the ring systems representing a formidable synthetic challenge. Herein, strategies for the total synthesis of such complex natural products are reviewed for the first time by using 26 representative studies. Methods for constructing the bridged ring system and bridgehead double bond have been emphasized, including syntheses of the same natural product by different research groups using different strategies, to showcase the diversity of thought and creativity in this area. The total synthesis of these natural products not only provides precious bioactive substances and promising candidates for drug discovery but also has stimulated incredible advances in the development of new strategies and synthetic methods.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule on T-cells, plays a key role in tumorigenesis and progression. In the present study, we investigated the effects of three polymorphisms in the CTLA-4 gene on the risk of epithelial ovarian cancer and the clinical outcomes of patients.A case-control study was performed in 527 epithelial ovarian cancer patients and 532 controls. Genotypes of three polymorphisms were determined by polymerase chain reaction/ligase detection reaction. A survival analysis was performed in 346 patients who were followed up for more than 3 years and 208 patients who were followed up for more than 5 years.There were significant differences in the genotype and allele distribution frequencies of the rs5742909 C/T polymorphism in CTLA-4 between patients and controls (p = 0.009 and p = 0.04, respectively). Compared with the CC genotype, the CT + TT genotype may significantly decrease the risk of developing epithelial ovarian cancer (OR = 0.69, 95% CI = 0.52-0.91). However, no significant association between the rs231775 G/A and rs3087243 G/A polymorphisms and epithelial ovarian cancer risk was observed. The survival analysis showed that three polymorphisms may not be related to the clinical outcomes of patients.Our results suggested that the rs5742909 C/T polymorphism of CTLA-4 may decrease the genetic susceptibility to epithelial ovarian cancer among northern Chinese women.

This study aimed to develop a constitutive model for human periodontal ligament (PDL) by combining the hyperelastic and viscosity models. We performed the finite element analysis (FEA) to simulate the experimental processes of the PDL in vitro and in vivo tests to verify the developed model. The FEA results indicated that the simulative curves were consistent with the experimental curves in the PDL in vitro tests. Moreover, for the in vivo measurements, the simulative result of 0.6258 N was similar to the experimental value of 0.65 N. The study results can help orthodontists better understand the biomechanical characteristics of PDL.

Abnormal gene expression caused by epigenetic changes, including DNA methylation, is associated with the development and progression of endometriosis. Grainyhead-like 2 gene (GRHL2), a suppressor of epithelial–mesenchymal transition, has been suggested to be associated with the occurrence, progression and poor survival of a variety of cancers. Although endometriosis is a benign disease, it has the biological behaviour of migration and invasion as malignant tumor. This study aims to determine whether the abnormal expression of the GRHL2 caused by aberrant methylation of its promoter is associated with the pathogenesis of ovarian endometriosis. Our results demonstrated that GRHL2 promoter region was significantly hypermethylated in the ectopic endometrium of patients with ovarian endometriosis compared with the normal endometrium of control patients. In contrast, the levels of GRHL2 mRNA and protein were significantly lower in the ectopic endometrium than in the control endometrium. Correlation analysis showed the methylation levels of GRHL2 were significantly negatively correlated with the mRNA expression of GRHL2. Moreover, the in vitro results suggested that the knockdown of GRHL2 could significantly increase the invasion and migration ability of EECs and may promote ZEB1 and vimentin expression while decreasing the expression of E-cadherin in EECs. Taken together, these results suggest that the low expression of GRHL2 caused by hypermethylation of the GRHL2 promoter is associated with ovarian endometriosis. The knockdown of GRHL2 may be involved in the occurrence of endometriosis by increasing EEC migration and invasion. This study provides more evidence for the hypothesis that endometriosis may be an epigenetic regulatory disorder.

The first asymmetric total synthesis of the highly strained compound cerorubenic acid-III is reported. A type II intramolecular [5 + 2] cycloaddition allowed efficient and diastereoselective construction of the synthetically challenging bicyclo[4.4.1] ring system with a strained bridgehead (anti-Bredt) double bond in the final product. A unique transannular cyclization installed the vinylcyclopropane moiety with retention of the desired stereochemistry.

Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes with copy number alterations (deletion and duplication region), functional annotation was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region and duplication region. In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YSTs). Moreover, POU5F1 was the most significant mutated gene with mutation frequency >10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region and duplication region) was found in two YST and nuclear staining in two dysgerminomas tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I (DExD/H-box helicase 58)-like receptor, Toll-like receptor and nuclear factor (NF)-kappa. Keratin 4 (KRT4), ribosomal protein L14 (RPL14), proprotein convertase subtilisin/kexin type 6 (PCSK6), poly(A)-binding protein cytoplasmic 3 (PABPC3), and sterile alpha and TIR motif containing 1 (SARM1) mutations were detected in both peripheral blood and tumor samples. Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.Summary sentenceThe overall mutation rate was very low in MOGCTs, with an average of 0.97 mutations per Mb. POU5F1 was the most significant mutated gene with mutation frequency >10% in both CNA deletion and duplication region. KRT4, RPL14, PCSK6, PABPC3, and SARM1 mutations were detected in both peripheral blood and tumor samples.

BACKGROUND: Orthodontic force is often statically measured in general, and only the initial force derived from appliances can be assessed. OBJECTIVE: We aimed to investigate a technological method for measuring dynamic force using tooth movement simulation. METHODS: Tooth movement was simulated in a softened wax model. A canine tooth was selected for evaluation and divided into the crown and root. A force transducer was plugged in and fixed between the two parts for measuring force. Forces on this tooth were derived by ordinary nickel–titanium (Ni–Ti) wire, hyperelastic Ni–Ti wire, low-hysteresis (LH) Ti–Ni wire and self-made glass fibre-reinforced shape memory polyurethane (GFRSMPU) wire. These forces were measured after the tooth movement. RESULTS: The canine tooth moved to the desired location, and only a 0.2 mm deviation remained. The changing trends and magnitudes of forces produced by the wires were consistent with the data reported by other studies. The tooth had a higher moving velocity with ordinary Ni–Ti wires in comparison to the other wires. Force attenuation for the GFRSMPU wire was the lowest (40.17%) at the end of the test, indicating that it provided light but continuous force. CONCLUSIONS: Mimicked tooth movements and dynamic force measurements were successfully determined in tooth movement simulation. These findings could help with estimating treatment effects and optimising the treatment plan.

Polymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes.A total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database.The results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05-2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09-2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29-1.91, P 0.001 and HR = 1.31, 95% CI = 1.06-1.63, P = 0.013, respectively).TIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.

Novel methodology for efficient functionalization of tetrahydro-β-carbolines (THβCs) has been established via an unexpected oxidative rearrangement coupling reaction. Treatment of THβCs with photogenerated singlet oxygen (1O2) afforded unstable dioxetanes, followed by further transformation to construct new bond in the presence of TFA. This operationally simple protocol exhibits broadly functional group-tolerant and allows for last-stage functionalization of complex drug-like molecules.

Orthodontic tooth movement is mainly regulated by the biomechanical responses of loaded periodontal ligament (PDL). We investigated the effective intervals of orthodontic force in pure maxillary canine intrusion and extrusion referring to PDL hydrostatic stress and logarithmic strain. Finite element analysis (FEA) models, including a maxillary canine, PDL and alveolar bone, were constructed based on computed tomography (CT) images of a patient. The material properties of alveolar bone were non-uniformly defined using HU values of CT images; PDL was assumed to be a hyperelastic-viscoelastic material. The compressive stress and tensile stress ranging from 0.47 to 12.8 kPa and 18.8 to 51.2 kPa, respectively, were identified as effective for tooth movement; a strain 0.24% was identified as the lower limit of effective strain. The stress/strain distributions within PDL were acquired in canine intrusion and extrusion using FEA; root apex was the main force-bearing area in intrusion-extrusion movements and was more prone to resorption. Owing to the distinction of PDL biomechanical responses to compression and tension, the effective interval of orthodontic force was substantially lower in canine intrusion (80-90 g) than in canine extrusion (230-260 g). A larger magnitude of force remained applicable in canine extrusion. This study revised and complemented orthodontic biomechanical behaviours of tooth movement with intrusive-extrusive force and could further help optimize orthodontic treatment.

In this paper, the five-leg inverter-dual permanent magnet synchronous motor system is taken as the research object. To solve the problem of large steady-state speed fluctuation when applying the traditional model predictive control strategy, based on the mathematical models of the five-leg inverter and the dual permanent magnet synchronous motor, the causes of the fluctuation are analyzed, and then an improved model predictive control algorithm with error feedback is proposed. The algorithm makes full use of the high-speed operation ability of modern digital processor, and introduces the prediction value of error feedback correction model, so that the rolling optimization is not only based on the model, but also makes full use of the actual value of the feedback state variables. At the same time, the second-order Euler discrete method is used to further improve the model progress. Simulation and experimental results show that the model predictive control strategy with error feedback can effectively improve the steady-state speed control performance of the system while maintaining the dynamic performance of the original system and the decoupling control effect of the two motors.

The first and asymmetric total synthesis of cyclocitrinol, an unusual C25 steroid, has been accomplished in a linear sequence of 18 steps from commercially available compound 11. The synthetically challenging bicyclo[4.4.1] A/B ring system with a strained bridgehead (anti-Bredt) double bond of cyclocitrinol was constructed efficiently and diastereoselectively via a type II intramolecular [5 + 2] cycloaddition.

Accumulating evidence demonstrates that mifepristone (RU486) exhibits potent anti-proliferative effects on various cancer cell lines. Our recent work shows that its major metabolite metapristone (RU42633) is a good drug candidate for cancer metastatic chemoprevention. However, lack of an efficient method for synthesizing metapristone limited its further clinical development. Herein, an improved and efficient condition of N-demethylation of mifepristone with an excellent yield is described. The procedure presented here has several advantages including one-pot preparation, ease of synthesis, and large-scale feasibility.

Baicalin and its aglycone baicalein derived from Scutellaria baicalensis exhibited potent anticancer effects in various types of cancer cell lines. However, the unfavorable pharmaceutical properties became the main obstacle for their potential clinical development. With the aim of development of novel anticancer agents based on the skeleton of baicalin, a series of novel negletein derivatives were designed and synthesized. Among them, compound 8 (FZU-02,006) with an N,N-dimethylamino ethoxyl moiety at the C-6 position exhibited significant enhanced antiproliferative effect against HL-60 cells in vitro through regulating multisignaling pathways. These results revealed that compound 8 with the improved aqueous solubility (as HCl salt, >1 mg/ml) and enhanced antileukemia potency might serve as a promising lead for further development.

An efficient synthetic approach to access oroxin A from inexpensive baicalin (I) is developed.

Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized.