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Abstract Objective This study aimed to evaluate the effect of fence tray matching care (FTMC) in bracket bonding by measuring excess adhesive, as well as linear and angular deviations, and by comparing it with the half-wrapped tray (HWT). Materials and methods An intraoral scanner was used to acquire data on the maxillary dental arch of a patient with periodontitis.Furthermore, 20 maxillary dental arch models were 3D printed. Using 3Shape, PlastyCAD software, and 3D printing technology, 10 FTMC (method I) and HWT (method II) were obtained. By preoperative preparation, intraoperative coordination, and postoperative measurement, the brackets were transferred from the trays to the 3D-printed maxillary dental arch models. Additionally, the bracket’s excess adhesive as well as linear and angular deviations were measured, and the differences between the two methods were analyzed. Results Excess adhesive was observed in both methods, with FTMC showing less adhesive (P

Griseofulvin (GF), which is mainly extracted from Penicillium griseofulvum, is a heat-resistant, chlorine-containing non-polyene antifungal antibiotic. Previous research shows that GF has a variety of pharmacological effects, such as anti-inflammatory, antifungal, antiviral, and antitumor effects. In recent years, GF has received extensive attention for its antitumor effects as a natural compound, offering a low price, a wide range of uses, and other beneficial characteristics. However, no comprehensive review of GF pharmacological activity in tumors has been published so far. In order to fully elucidate the antitumor activities of GF, this review focuses on the antitumor potential and toxicity of GF and its derivatives, based on a literature search using PubMed, Web of Science, and other databases, to lay a good foundation for further research of GF and the development of new drugs for antitumor activities.

Isorhamnetin (ISO) is a phenolic compound belonging to flavonoid family, showcasing important in vitro pharmacological activities such as antitumor, anti-inflammation, and organ protection. ISO is predominantly extracted from Hippophae rhamnoides L. This plant is well-known in China and abroad because of its “medicinal and food homologous” characteristics. As a noteworthy natural drug candidate, ISO has received considerable attention in recent years owing to its low cost, wide availability, high efficacy, low toxicity, and minimal side effects. To comprehensively elucidate the multiple biological functions of ISO, particularly its antitumor activities and other pharmacological potentials, a literature search was conducted using electronic databases including Web of Science, PubMed, Google Scholar, and Scopus. This review primarily focuses on ISO’s ethnopharmacology. By synthesizing the advancements made in existing research, it is found that the general effects of ISO involve a series of in vitro potentials, such as antitumor, protection of cardiovascular and cerebrovascular, anti-inflammation, antioxidant, and more. This review illustrates ISO’s antitumor and other pharmacological potentials, providing a theoretical basis for further research and new drug development of ISO.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.

Cancer is a borderless global health challenge that continues to threaten human health. Studies have found that oxidative stress (OS) is often associated with the etiology of many diseases, especially the aging process and cancer. Involved in the OS reaction as a key transcription factor, Nrf2 is a pivotal regulator of cellular redox state and detoxification. Nrf2 can prevent oxidative damage by regulating gene expression with antioxidant response elements (ARE) to promote the antioxidant response process. OS is generated with an imbalance in the redox state and promotes the accumulation of mutations and genome instability, thus associated with the establishment and development of different cancers. Nrf2 activation regulates a plethora of processes inducing cellular proliferation, differentiation and death, and is strongly associated with OS-mediated cancer. What’s more, Nrf2 activation is also involved in anti-inflammatory effects and metabolic disorders, neurodegenerative diseases, and multidrug resistance. Nrf2 is highly expressed in multiple human body parts of digestive system, respiratory system, reproductive system and nervous system. In oncology research, Nrf2 has emerged as a promising therapeutic target. Therefore, certain natural compounds and drugs can exert anti-cancer effects through the Nrf2 signaling pathway, and blocking the Nrf2 signaling pathway can reduce some types of tumor recurrence rates and increase sensitivity to chemotherapy. However, Nrf2’s dual role and controversial impact in cancer are inevitable consideration factors when treating Nrf2 as a therapeutic target. In this review, we summarized the current state of biological characteristics of Nrf2 and its dual role and development mechanism in different tumor cells, discussed Keap1/Nrf2/ARE signaling pathway and its downstream genes, elaborated the expression of related signaling pathways such as AMPK/mTOR and NF-κB. Besides, the main mechanism of Nrf2 as a cancer therapeutic target and the therapeutic strategies using Nrf2 inhibitors or activators, as well as the possible positive and negative effects of Nrf2 activation were also reviewed. It can be concluded that Nrf2 is related to OS and serves as an important factor in cancer formation and development, thus provides a basis for targeted therapy in human cancers.

Solid tumors can be divided into benign solid tumors and solid malignant tumors in the academic community, among which malignant solid tumors are called cancers. Cancer is the second leading cause of death in the world, and the global incidence of cancer is increasing yearly New cancer patients in China are always the first. After the concept of stem cells was introduced in the tumor community, the CSC markers represented by ALDH1 have been widely studied due to their strong CSC cell characteristics and potential to be the driving force of tumor metastasis. In the research results in the past five years, it has been found that ALDH1 is highly expressed in various solid cancers such as breast cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer, cervical cancer, esophageal cancer, ovarian cancer, head,and neck cancer. ALDH1 can activate and transform various pathways (such as the USP28/MYC signaling pathway, ALDH1A1/HIF-1α/VEGF axis, wnt/β-catenin signaling pathway), as well as change the intracellular pH value to promote formation and maintenance, resulting in drug resistance in tumors. By targeting and inhibiting ALDH1 in tumor stem cells, it can enhance the sensitivity of drugs and inhibit the proliferation, differentiation, and metastasis of solid tumor stem cells to some extent. This review discusses the relationship and pathway of ALDH1 with various solid tumors. It proposes that ALDH1 may serve as a diagnosis and therapeutic target for CSC, providing new insights and new strategies for reliable tumor treatment.

Abstract With CA16, enterovirus-71 is the causative agent of hand foot and mouth disease (HFMD) which occurs mostly in children under 5 years-old and responsible of several outbreaks since a decade. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death; EV71 has been identified in all severe cases. Therefore, it is actually one of the most public health issues that threatens children’s life. $$3{\rm C}^{{\rm pro}}$$ 3 C pro is a protease which plays important functions in EV71 infection. To date, a lot of $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors have been tested but none of them has been approved yet. Therefore, a drug screening is still an utmost importance in order to treat and/or prevent EV71 infections. This work highlights the EV71 life cycle, $$3{\rm C}^{{\rm pro}}$$ 3 C pro functions and $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors recently screened. It permits to well understand all mechanisms about $$3{\rm C}^{{\rm pro}}$$ 3 C pro and consequently allow further development of drugs targeting $$3{\rm C}^{{\rm pro}}$$ 3 C pro . Thus, this review is helpful for screening of more new $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors or for designing analogues of well known $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors in order to improve its antiviral activity.

Abstract Rapid metabolism differentiates cancer cells from normal cells and relies on anaplerotic pathways. However, the mechanisms of anaplerosis‐associated enzymes are rarely understood. The lack of potent and selective antimetabolism drugs restrains further clinical investigations. A small molecule ZY‐444 ((N4‐((5‐(4‐(benzyloxy)phenyl)‐2‐thiophenyl)methyl)‐N2‐isobutyl‐2,4‐pyrimidinediamine) is discovered to inhibit cancer cell proliferation specifically, having potent efficacies against tumor growth, metastasis, and recurrence. ZY‐444 binds to cellular pyruvate carboxylase (PC), a key anaplerotic enzyme of the tricarboxylic acid cycle, and inactivates its catalytic activity. PC inhibition suppresses breast cancer growth and metastasis through inhibiting the Wnt/β‐catenin/Snail signaling pathway. Lower PC expression in patient tumors is correlated with significant survival benefits. Comparative profiles of PC expression in cancer versus normal tissues implicate the tumor selectivity of ZY‐444. Overall, ZY‐444 holds promise therapeutically as an anti‐cancer metabolism agent.

Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biological function, clinical significance, and therapeutic targeted value of PELP1 in gastric cancer (GC).Methods: The expression status of PELP1 in GC cell lines or tissues was analyzed through bioinformatics data mining. Thirty-six GC tissue chip was applied to demonstrate the results of bioinformatics data mining assayed by immunohistochemical method. The expression status of PELP1 in GC cell lines was also analyzed using western blot. Correlation analysis between PELP1 expression and clinicopathological parameter was performed. Kaplan-Meier survival analysis was applied to analyze the relationship between PELP1 expression and total survival time. Three pairs of siRNA were designed to silence the expression of PELP1 in GC. After PELP1 was silenced by siRNA or activated by saRNA, the growth, plate colony formation, migration and invasion ability of the GC cell or normal gastric epithelium cell line was tested in vitro. Cell cycle was tested by flow cytometry. Nude mice xenograft experiment was performed after PELP1 was silenced. The downstream molecular pathway regulated by PELP1 was explored. Molecular docking tool was applied to combine chlorpromazine with PELP1. The inhibitory effect of chlorpromazine in GC was assayed, then it was tested whether PELP1 was a therapeutic target of chlorpromazine in GC.Results: PELP1 expression was elevated in GC cell lines and clinical GC tissue samples. PELP1 silence by siRNA compromised the malignant traits of GC. PELP1 expression positively correlated with tumor invasion depth, lymph node metastasis, tissue grade, TNM stage, but had no correlation with patient age, sex, tumor size, and tumor numbers. Kaplan-Meier survival analysis revealed high PELP1 expression had a shorter survival period in GC patients after follow-up. Q-PCR and western blot revealed PELP1 suppression in GC decreased expression of the c-Src-PI3K-ERK pathway. It was also implied that chlorpromazine (CPZ) can inhibit the malignant traits of GC and downregulate the expression of PELP1.Conclusions: In a word, PELP1 is an oncogene in gastric cancer and c-Src-PI3K-ERK pathway activation may be responsible for its tumorigenesis, PELP1 may be a potential therapeutic target of chlorpromazine in GC.

Abstract Background Lycorine has been revealed to inhibit the development of many kinds of malignant tumors, including glioblastoma multiforme (GBM). Although compelling evidences demonstrated Lycorine’s inhibition on cancers through some peripheral mechanism, in-depth mechanism studies of Lycotine’s anti-GBM effects still call for further exploration. Epidermal Growth Factor Receptor (EGFR) gene amplification and mutations are the most common oncogenic events in GBM. Targeting EGFR by small molecular inhibitors is a rational strategy for GBM treatment. Methods The molecular docking modeling and in vitro EGFR kinase activity system were employed to identify the potential inhibitory effects of Lycorine on EGFR. And the Biacore assay was used to confirm the direct binding status between Lycorine and the intracellular EGFR (696–1022) domain. In vitro assays were conducted to test the suppression of Lycorine on the biological behavior of GBM cells. By RNA interference, EGFR expression was reduced then cells underwent proliferation assay to investigate whether Lycorine’s inhibition on GBM cells was EGFR-dependent or not. RT-PCR and western blotting analysis were carried out to investigate the underlined molecular mechanism that Lycorine exerted on EGFR itself and EGFR signaling pathway. Three different xenograft models (an U251-luc intracranially orthotopic transplantation model, an EGFR stably knockdown U251 subcutaneous xenograft model and a patient-derived xenograft model) were performed to verify Lycorine’s therapeutic potential on GBM in vivo. Results We identified a novel small natural molecule Lycorine binding to the intracellular EGFR (696–1022) domain as an inhibitor of EGFR. Lycorine decreased GBM cell proliferation, migration and colony formation by inducing cell apoptosis in an EGFR-mediated manner. Furthermore, Lycorine inhibited the xenograft tumor growths in three animal models in vivo. Besides, Lycorine impaired the phosphorylation of EGFR, AKT, which were mechanistically associated with expression alteration of a series of cell survival and death regulators and metastasis-related MMP9 protein. Conclusions Our findings identify Lycorine directly interacts with EGFR and inhibits EGFR activation. The most significant result is that Lycorine displays satisfactory therapeutic effect in our patient-derived GBM tumor xenograft, thus supporting the conclusion that Lycorine may be considered as a promising candidate in clinical therapy for GBM.

Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.

Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC) cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.

Prostate cancers often become castration resistant due to alternative expression of androgen receptor (AR) splice variants. Here, the authors screened a library of natural compounds and identified Ailanthone as a potent inhibitor of AR through its binding to the co-chaperone protein p23 that, by preventing AR interaction with HSP90, results in ubiquitin/proteasome-mediated degradation of the receptor.

Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs), highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs), which have shown favorable anti-tumor activity with low toxicity in clinical investigations, are a promising class of anticancer therapeutics. Here, we screened our compound library to explore small molecules that possess anti-HDAC activity and identified a novel HDACI, YF479. Suberoylanilide hydroxamic acid (SAHA), which was the first approved HDAC inhibitor for clinical treatment by the FDA, was as positive control in our experiments. We further demonstrated YF479 abated cell viability, suppressed colony formation and tumor cell motility in vitro. To investigate YF479 with superior pharmacodynamic properties, we developed spontaneous and experimental breast cancer animal models. Our results showed YF479 significantly inhibited breast tumor growth and metastasis in vivo. Further study indicated YF479 suppressed both early and end stages of metastatic progression. Subsequent adjuvant chemotherapy animal experiment revealed the elimination of local-regional recurrence (LRR) and distant metastasis by YF479. More important, YF479 remarkably prolonged the survival of tumor-bearing mice. Intriguingly, YF479 displayed more potent anti-tumor activity in vitro and in vivo compared with SAHA. Together, our results suggest that YF479, a novel HDACI, inhibits breast tumor growth, metastasis and recurrence. In light of these results, YF479 may be an effective therapeutic option in clinical trials for patients burdened by breast cancer.

Nonautonomous nonlinear (NN) systems have broad application prospects and significant research value in nonlinear science. In this paper, a new synchronization type—namely, generalized bi-variable function projective synchronization (GBVFPS)—is proposed. The scaling function matrix of GBVFPS is not one-variable but bi-variable. This indicates that the GBVFPS can be transformed into various synchronization types such as projective synchronization (PS), modified PS, function PS, modified function PS, and generalized function PS. In order to achieve the GBVFPS in two different NN systems with various perturbations, by designing a novel Zhang neuro-PID controller, an effective and anti-perturbation GBVFPS control method is proposed. Rigorous theoretical analyses are presented to prove the convergence performance and anti-perturbation ability of the GBVFPS control method, especially its ability to suppress six different perturbations. Besides, the effectiveness, superiority, and anti-perturbation ability of the proposed GBVFPS control method are further substantiated through two representative numerical simulations, including the synchronization of two NN chaotic systems and the synchronization of two four-dimensional vehicular inverted pendulum systems.

IntroductionAnti-neutrophil cytoplasm antibody (ANCA)-associated-vasculitis and anti-glomerular basement membrane (GBM) disease are types of autoimmune diseases that are characterized by the presence of circulating autoantibodies. Most patients with these diseases experience sudden onset, rapid progress, and poor prognosis. The purpose of the present article is to report a case of ANCA-associated vasculitis with anti-GBM disease and two types of tumors.Case ReportA 63-year-old Chinese woman who underwent resection for rectal cancer 6 years before and for lung adenocarcinoma 4 years before, presented with fever and nasal obstruction, for the past 2 months and chondritis of an ear for the past 1 month. The patient failed to respond to an anti-infection treatment at local and higher-level hospitals with the first episode of “recurrent sinusitis and fever.” Later, systemic symptoms such as fatigue, numbness of the limbs, and auricular chondritis gradually aggravated, followed by an increase in inconspicuous hematuria, proteinuria, and serum creatinine level. After admission, the GBM antibody, C-ANCA, and PR3 were positive. The renal puncture was diagnosed as anti-glomerular basement membrane antibody disease. After treatment, her serum creatinine decreased to 104 umol/l.DiscussionIn the present report, we introduced the case of a rare double-positive disease in a patient with two types of tumors. Importantly, we noted that colon cancer and lung cancer, PR3, and anti-GBM disease may be related to their pathogenesis and manifestations. Further research is warranted to confirm these hypotheses.

This paper studies the control of a class of 3D chaotic systems with uncertain parameters and external disturbances. A new method which is referred as the analytical solution approach is firstly proposed for constructing Lyapunov function. Then, for suppressing the trajectories of the 3D chaotic system to its equilibrium point 00,0,0, a novel fast convergence controller containing parameter λ which determines the convergence rate of the system is presented. By using the designed Lyapunov function, the stability of the closed-loop system is proved via the Lyapunov stability theorem. Computer simulations are employed to a new chaotic system to illustrate the effectiveness of the theoretical results.

This article is concerned with the exponential synchronization of a class of the chaotic systems with external disturbance via the saturation control. Through appropriate coordinate transformation, the exponential synchronization is translated into the asymptotic stability of the error system. By using the Lyapunov stability theory, a novel sufficient condition which possesses the exponential convergence rate λ is presented. The rich choices of the exponential convergence rate λ turn our scheme more general than some existing approaches. Numerical simulations are employed to the Genesio chaotic system and the Coullet chaotic system to illustrate the ability and effectiveness of the presented approach.

A genetic linkage map of chromosome 6 was constructed by using 270 recombinant inbred lines originated from an upland cotton cross (Yumian 1 × T586) F2 population. The genetic map included one morphological (T1) and 18 SSR loci, covering 96.2 cM with an average distance of 5.34 cM between two markers. Based on composite interval mapping (CIM), QTL(s) affecting lint percentage, fiber length, fiber length uniformity, fiber strength and spiny bollworm resistance ( Earias spp.) were identified in the t1 locus region on chromosome 6. The allele(s) originating from T586 of QTLs controlling lint percentage increased the trait phenotypic value while the alleles originating from Yumian 1 of QTLs affecting fiber length, fiber length uniformity, fiber strength and spiny bollworm resistance increased the trait phenotypic value. [ABSTRACT FROM AUTHOR]

This paper investigates the control and synchronization of a class of 3-D uncertain fractional-order chaotic systems with external disturbances. The adding one power integrator control scheme, which is the generalization of the traditional backstepping method, is used to investigate the global stability of the control and synchronization manifold. As a result, several criteria for chaos control and synchronization are obtained. Compared with the previous results, the presented strategies can not only be applied to a class of strict-feedback systems but also be applied to more general class of fractional-order chaotic systems. In addition, the proposed controllers are robust against uncertain parameters and external disturbances. To validate the effectiveness of the proposed criteria, two illustrative examples are given.

We presented a compositionally graded hole reservoir layers(HRL) - an AlGaN/GaN super lattice hole reservoir layer with Al mole fraction multi-step gradient from high to low (GSL-HRL) in this paper. The designed LED with compositionally step graded HRL shows comparable low operating voltage and less efficiency droop. Simulation results reveal that this graded HRL could reserve the hole effectively and the hole in HRL can be energized by the strong electric field due to the polarization caused by different Al contents AlxGa1-xN layers. Such a design makes hole travel across the p-type EBL and inject into the MQWs more efficiently and smoothly. The novel structure of HRL improves the performance of the LED significantly and gives a promising application in high power GaN-based LED in the future.