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1.
Prostate ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022812

RESUMO

BACKGROUND: Nerves are key factors in prostate cancer (PCa) progression. Here, we propose that neuropeptide Y (NPY) nerves are key regulators of cancer-nerve interaction. METHODS: We used in vitro models for NPY inhibition studies and subsequent metabolomics, apoptotic and migration assays, and nuclear transcription factor-κB (NF-κB) translocation studies. Human naïve and radiated PCa tissues were used for NPY nerve density biomarker studies. Tissues derived from a Botox denervation clinical trial were used to corroborate metabolomic changes in humans. RESULTS: Cancer cells increase NPY positive nerves in vitro and in preneoplastic human tissues. NPY-specific inhibition resulted in increased cancer apoptosis, decreased motility, and energetic metabolic pathway changes. A comparison of metabolomic response in NPY-inhibited cells with the transcriptome response in human PCa patients treated with Botox showed shared 13 pathways, including the tricarboxylic acid cycle. We identified that NF-κB is a potential NPY downstream mediator. Using in vitro models and tissues derived from a previous human chemical denervation study, we show that Botox specifically, but not exclusively, inhibits NPY in cancer. Quantification of NPY nerves is independently predictive of PCa-specific death. Finally, NPY nerves might be involved in radiation therapy (RT) resistance, as radiation-induced apoptosis is reduced when PCa cells are cocultured with dorsal root ganglia/nerves and NPY positive nerves are increased in prostates of patients that failed RT. CONCLUSION: These data suggest that targeting the NPY neural microenvironment may represent a therapeutic approach for the treatment of PCa and resistance through the regulation of multiple oncogenic mechanisms.

2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5733-5736, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019276

RESUMO

Populations around the world are rapidly ageing. Age-friendly environments address the significance of continuous inhome vital sign monitoring. Impulse Radio Ultra-WideBand (IR-UWB) radar serves as a household healthcare assistance, providing non-contact vital sign monitoring without privacy issues and illumination limitation. However, the body movements bring difficulty in extracting heartbeat from radar signals, let alone obtaining complete information with body occlusions among multiple targets. This paper proposes a Multiple Moving Targets Heartbeat Estimation And Recovery (MMT-HEAR) approach to extract vital signs using IR-UWB radars. CLEAN and Joint Probability Data Association (JPDA) algorithms are firstly performed on each radar to estimate target-to-antenna distances of multiple targets. Considering signal obstruction and attenuation for targets occluded by others, the location-based distance optimization is proposed to refine these distances by combining information from all radars. Then the mapping from signal amplitudes to refined distances is introduced and combined with the Variational Nonlinear Chirp Mode Decomposition (VNCMD) to extract vital signs with body movements. To the best of our knowledge, this is the first attempt to monitor vital signs of multiple moving targets with radars. The averaging accuracy for two moving targets heartbeat monitoring during a 20-minutes observation is 85.93% with MMT-HEAR. Compared to two other conventional methods, the MMT-HEAR approach yields improvements of 16.11% and 10.16%, revealing the efficiency and robustness of this proposed approach.

3.
Phys Chem Chem Phys ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021271

RESUMO

The design and characterization of the heteronuclear group 14 C[triple bond, length as m-dash]E (E = Si, Ge, Sn, Pb) triple bonds have attracted intensive interest in the past few decades. In the current work, utilizing the advantages of N-heterocyclic carbenes (NHCs) and Lewis acid-base pair strategy, we theoretically designed a new class of compounds III-1, i.e., (NHCAR)C[triple bond, length as m-dash]E(Al(C6F5)3). Quantum chemical calculations showed that these singlet compounds possess very favourable isomerization, fragmentation and dimerization stabilities at the B3LYP/def2-TZVPP//B3LYP/def2-SVP level. The calculated bond lengths of CE in III-1 are 1.63 Å for Si, 1.70 Å for Ge, 1.91 Å for Sn and 2.01 Å for Pb, respectively, which are close to or even shorter than the known C[triple bond, length as m-dash]E bond lengths. In addition, the significant Mayer bond order values, two orthogonal π orbitals and one σ orbital between the C and E atoms also indicate the characteristics of triple bonds. Based on several bonding analyses, strong delocalization is found to exist between the C[triple bond, length as m-dash]E core and NHCAR forming a weak C[double bond, length as m-dash]C double bond. Hence, such obtained C[triple bond, length as m-dash]E species also can be described by their resonace structures as cunmulene analogs. In all, III-1 proposed here not only presents a universal C[triple bond, length as m-dash]E motif for all the heavier group 14 elements, but also provides a new strategy for the design and synthesis of heteronuclear group 14 triple bonds in the future.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33038198

RESUMO

STUDY DESIGN: A case control study. OBJECTIVE: The aim of this study was to identify the potential impact of cervical spine malalignment on muscle parameters. SUMMARY OF BACKGROUND DATA: Muscular factors are associated with cervical alignment. Nevertheless, only muscle dimensions or imaging changes have been evaluated, function of cervical muscles has scarcely been investigated. METHODS: 34 patients diagnosed as cervical spine degeneration associated with cervical malalignment and 32 control subjects were included in this case control study. Visual analogue scale (VAS) and the neck disability index (NDI) were used. The sagittal alignment parameters and cervical range of motion (ROM) were measured on cervical spine lateral radiographs, included C2-C7 lordosis, C2-C7 sagittal vertical axis (C2-C7 SVA), cervical gravity-sagittal vertical axis (CG-SVA), T1-Slope, and spinal canal angle (SCA). Surface Electromyography (SEMG)-based flexion-relaxation ratio (FRR) was measured. RESULTS: The result showed VAS score of the neck significantly lower in controls (p<0.05), C2-C7 lordosis, C2-C7 SVA, CG-SVA, T1-Slope and ROM showed significant different (p<0.001) between malalignment group and control group, FRR of splenius capitis (FRRSpl) and upper trapezius (FRRUTr) of the malalignment group were lower than in the control group, which correlated well with NDI (rSpl = -0.181 rUTr = -0.275), FRRSpl correlated well with VAS (rSpl = -0.177). FRRSpl correlated strongly with C2-C7 SVA (r = 0.30), CG-SVA (r = 0.32), T1-Slope (r = 0.17), ROM (r = 0.19), FRRUTr correlated with C2-C7 lordosis (r = -0.23), CG-SVA (r = 0.19), T1-Slope (r = 0.28), ROM (r = 0.23). CONCLUSION: Cervical malalignment patients had more tensional posterior cervical muscle and poor muscle functions. CG-SVA showed advantages in evaluating cervical malalignment. LEVEL OF EVIDENCE: 3.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33059441

RESUMO

Obtaining a perovskite light-absorbing layer with good crystallization, low defect concentration, good stability, and well-matched energy levels is critical to obtaining high-efficiency perovskite solar cells (PSCs). Here, a hybrid PSC with a graded band gap is explored using MAPbBr3 (MA = CH3NH3) and MAPbBr0.9I2.1 quantum dots (QDs) as component cells. We have creatively designed a solar cell device with a double-QD structure [indium tin oxide (ITO)/SnO2/perovskite:MAPbBr3 QDs/MAPbBr0.9I2.1 QDs/Spiro-OMeTAD/Au]. A better crystal film of the perovskite absorption layer can be obtained because the MAPbBr3 QDs are doped in an antisolvent, which induces nucleation and growth in the polycrystalline perovskite. In addition, we expect that digestive ripening occurred in the crystallization, and the oleic acid ligands on the surface of the QDs disintegrate during the doping process and transfer to the surface of the perovskite absorption layer finally; it follows that the hydrophobicity and stability of the perovskite film are greatly enhanced. Moreover, a thin film of MAPbBr0.9I2.1 QDs is introduced between the perovskite absorption layer and the hole layer, acting as an energy-level ladder, which leads to well-matched energy levels, an increase in fill factor (FF), and an enhanced hole transport capability. In particular, the mechanism of the crystallization process involving the effect of oleic acid ligands on the interior and surface of the perovskite film is fully discussed here. The final research results from the PSCs show that both high efficiency and long-term stability are achieved successfully by this design strategy.

6.
Aging (Albany NY) ; 122020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049716

RESUMO

While cancer immunotherapy has been remarkably successful in some malignancies, some cancers derive limited benefit from current immunotherapies. Here, we combined immune landscape signatures with hepatocellular carcinoma clinical and prognostic features to classify them into distinct subtypes. The immunogenomic profiles, stromal cell features and immune cell composition of the subtypes were then systematically analyzed. Two independent prognostic indexes were established based on 6 immune-related genes and 17 differentially expressed genes associated with stromal cell content. These indexes were significantly correlated with tumor mutation burden, deficient DNA mismatch repair and microsatellite instability. In addition, tumor-infiltrating lymphocytes, including activated NK cells, resting memory CD4 T-cells, eosinophils, and activated mast cells were significantly correlated with hepatocellular carcinoma survival. In conclusion, we have comprehensively described the immune landscape signatures and identified prognostic immune-associated biomarkers of hepatocellular carcinoma. Our findings highlight potential novel avenues for improving responses to immunotherapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33050721

RESUMO

In response to reports of people experiencing varying levels of anxiety and depression during the outbreak of COVID-19, researchers have argued that exposure to related information on social media is a salient contributing factor. Based on the integrated model of ruminative response style and the diathesis-stress model, it has been suggested that incorporating rumination and mindfulness may elucidate the potential mechanism underlying the aforementioned association. This study aimed to examine the mediating role of rumination and the moderating role of mindfulness in the association between social media exposure (SME) to COVID-19 information and psychological distress. The results from online questionnaire responses of 439 college students from two universities in Wuhan, Hubei Province, showed that rumination mediated the association between SME and psychological distress. Furthermore, mindfulness was revealed as a protective factor that buffered the adverse effect of SME on psychological distress through rumination. These findings advance a better understanding of the formation process of psychological symptoms during the COVID-19 pandemic and provide insights regarding effective interventions for adverse mental health consequences in college students.

8.
Aging (Albany NY) ; 122020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040048

RESUMO

Traumatic brain injury (TBI) is regarded as a high-risk factor for Alzheimer's disease (AD). Asparaginyl endopeptidase (AEP), a lysosomal cysteine protease involved in AD pathogenesis, is normally activated under acidic conditions and also in TBI. However, both the molecular mechanism underlying AEP activation-mediated TBI-related AD pathologies, and the role of AEP as an AD therapeutic target, still remain unclear. Here, we report that TBI induces hippocampus dependent cognitive deficit and synaptic dysfunction, accompanied with AEP activation, I2PP2A (inhibitor 2 of PP2A, also called SET) mis-translocation from neuronal nucleus to cytoplasm, an obvious increase in AEP interaction with SET, and tau hyperphosphorylation in hippocampus of rats. Oxygen-glucose deprivation (OGD), mimicking an acidic condition, also leads to AEP activation, SET mis-translocation, PP2A inhibition, tau hyperphosphorylation, and a decrease in synaptic proteins, all of which are abrogated by AEP inhibitor AENK in primary neurons. Interestingly, AENK restores SET back to the nucleus, mitigates tau pathologies, rescuing TBI-induced cognitive deficit in rats. These findings highlight a novel etiopathogenic mechanism of TBI-related AD, which is initiated by AEP activation, accumulating SET in cytoplasm, and favoring tau pathology and cognitive impairments. Lowering AEP activity by AEP inhibitor would be beneficial to AD patients with TBI.

9.
Elife ; 92020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064077

RESUMO

In plants, establishment of de novo DNA methylation is regulated by the RNA-directed DNA methylation (RdDM) pathway. RdDM machinery is known to concentrate in the Cajal body, but the biological significance of this localization has remained elusive. Here, we show that the antiviral methylation of the Tomato yellow leaf curl virus (TYLCV) genome requires the Cajal body in Nicotiana benthamiana cells. Methylation of the viral genome is countered by a virus-encoded protein, V2, which interacts with the central RdDM component AGO4, interfering with its binding to the viral DNA; Cajal body localization of the V2-AGO4 interaction is necessary for the viral protein to exert this function. Taken together, our results draw a long sought-after functional connection between RdDM, the Cajal body, and antiviral DNA methylation, paving the way for a deeper understanding of DNA methylation and antiviral defences in plants.

10.
Front Endocrinol (Lausanne) ; 11: 543246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071967

RESUMO

Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism, and extra-endocrine features. MEN2 syndrome includes two clinically distinct forms subtyped as MEN2A and MEN2B. Nearly all MEN2 cases are caused by germline mutations of the RET proto-oncogene. In this review, we propose "5P" strategies for management of MEN2: prevention, prediction, personalization, psychological support, and participation, which could effectively improve clinical outcomes of patients. Based on RET mutations, MEN2 could be prevented through prenatal diagnosis or preimplantation genetic testing. Identification of pathogenic mutations in RET can enable early diagnosis of MEN2. Combining RET mutation testing with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could allow risk stratification and accurately prediction of MEN2 progression, thus facilitating implementation of personalized precision treatments to increase disease-free survival and overall survival. Furthermore, increased awareness of MEN2 is needed, which requires participation of physicians, patients, family members, and related organizations. Psychological support is also important for patients with MEN2 to promote comprehensive management of MEN2 symptoms. The "5P" strategies for management of MEN2 represent a typical clinical example of precision medicine. These strategies could effectively improve the health of MEN2 patient, and avoid adverse outcomes, including death and major morbidity, from MEN2.

11.
Braz J Cardiovasc Surg ; 35(4): 484-489, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32864928

RESUMO

OBJECTIVE: To investigate the effect of Shenfu (SF) injection on donor heart preservation. METHODS: Twelve pigs were randomly divided into SF group (n=6) and control group (n=6). After eight hours of perfusion, the differences in hemoglobin, the expression of Bcl-2 and BAX, and changes in the myocardial ultrastructure were compared to illustrate the effects of SF injection in heart preservation. RESULTS: The differences in free hemoglobin between the SF group and the control group were statistically significant (P=0.001), and there was significant interaction of groups with times (P=0.019), but the perfusion time may not be associated with the hemoglobin concentration (P=0.616). According to Western blotting analysis, the expression of Bcl-2 was higher in the SF group than in the control group, while the expression of BAX was not different between the two groups. As to ultrastructural changes, both groups exhibited mitochondrial swelling and myofilament lysis, but the degree of damage in the SF group was smaller. CONCLUSION: Our study suggests that the application of SF injection for heart preservation may protect against cardiomyocytes and erythrocytes apoptosis, and Bcl-2 protein may play a role in these physiological processes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32897694

RESUMO

High-performance photodetectors require efficient photogeneration and charge transport. Perovskite quantum dots (PQDs) have received enormous interest for applications in optoelectronics due to their high photogeneration efficiency. However, they offer meager carrier transport. Reduced graphene oxide (RGO) exhibits inferior photoresponse compared to materials such as quantum dots. An effective synthesis protocol to grow PQDs from the RGO lattice may facilitate direct charge transfers from PQDs to RGO, which could not be accomplished by mixing individual PQDs with RGO or making a bilayer. At ambient condition, the photodetector fabricated with the PQD-RGO superstructure showed high responsivity of 1.07 × 103 A/W, detectivity of 1 × 1013 Jones as well as sharp switching in the visible wavelength. After 3 months in an unencapsulated sample, the photocurrent was decreased ∼10% of its initial value while preserving speed and cycle stability at ambient condition.

14.
Cell Death Dis ; 11(9): 766, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943607

RESUMO

Anlotinib (AL3818), a novel multi-targeted receptor tyrosine kinase inhibitor, has recently been proven to be an antitumour drug. This study aimed to explore the antitumour effect of anlotinib and its underlying molecular mechanisms in human pancreatic cancer (PC) cells. The anti-proliferative effect of anlotinib for three PC cell lines was validated using CCK-8, colony formation and EdU detection assays. Cell cycle, cell apoptosis, and reactive oxygen species (ROS) detection assays, a PC xenograft model and immunohistochemistry were performed to elucidate the mechanisms by which anlotinib induced tumour lethality in vitro and in vivo. These results demonstrated that anlotinib inhibited proliferation, induced G2/M phase arrest and triggered apoptosis in PC cell lines. Anlotinib induced PC's apoptosis through the accumulation of ROS which activated the endoplasmic reticulum (ER) stress via PERK/p-eIF2α/ATF4 pathway. Furthermore, we demonstrated that the expression level of Nrf2, an antioxidant protein, increased with anlotinib treatment. Nrf2 knockdown enhanced the pro-apoptotic effect of anlotinib and the expression of the PERK/p-eIF2α/ATF4 pathway. The in vivo results suggested that suppressing Nrf2 improved the antitumour effect of anlotinib on PC cells. These data indicated that the apoptotic effect of anlotinib on PC cells was induced by ER stress via the accumulation of ROS. In the future, anlotinib combined with an Nrf2 inhibitor may provide a new therapeutic strategy for the treatment of human PC.

15.
J Am Heart Assoc ; 9(18): e017499, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32875935

RESUMO

Background The prognostic role of B-type natriuretic peptide (BNP) in stroke has been suggested, but limited studies have shown mixed results and unknown underlying mechanisms. DNA methylation, a molecular modification that alters gene expression, may represent a candidate mechanism for this purpose. We aimed to examine the associations of BNP and methylation of its coding gene (natriuretic peptide B [NPPB]) with the functional outcome in a large sample of patients with acute ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Methods and Results Leveraging participants from CATIS with available specimens, serum proBNP (equimolarly produced with BNP) was measured in 3216 patients (mean age, 62 years; 64% men), and peripheral blood DNA methylation of the NPPB promoter was quantified by targeted bisulfite sequencing in 806 patients (mean age, 62 years; 54% men). The functional outcome was defined as an ordered modified Rankin Scale score assessed at 14 days or hospital discharge after stroke onset. Mediation analysis was conducted to test the potential mediating effect of proBNP on the relationship between NPPB methylation and functional outcome. The results showed that a higher level of proBNP was significantly associated with a higher risk of having a poorer functional outcome (odds ratio [OR], 1.14; P=0.006). Every 5% of hypermethylation at 2 (Chr1:11919160 [OR, 0.93; P=0.022] and Chr1:11918989 [OR, 0.92; P=0.032]) of 11 CpG loci assayed was associated with 7% and 8% lower risk, respectively, of having a poor functional outcome. In addition, proBNP was negatively correlated to hypermethylation at 1 CpG (Chr1:11918989 [ß=-0.029; P=0.009]) and mediated approximately 7.69% (95% CI, 2.50%-13.82%) of the association between this CpG methylation and the functional outcome. Conclusions Hypermethylation at the NPPB promoter is associated with the functional outcome after ischemic stroke, at least partially by suppressing BNP expression or excretion.

16.
J Orthop Surg Res ; 15(1): 387, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900383

RESUMO

BACKGROUND: The objective of the study was to evaluate our innovative percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) for the treatment of lumbar degenerative diseases. METHODS: Two fresh-frozen human cadavers with soft tissues were donated for the experiment. Both cadavers had no history of previous spine surgery. The PE-TLIF surgery was performed on 3 levels (L4-5 of the first one, and L3-4, L4-5 of the second one) in October 2015. The PE-TLIF technique mainly included the following aspects: primary guide pins and a specially designed superior articular process (SAP) guide insertion, working channel setup, endoscopic decompression and fusion, and pedicle screw implantation and fixation. Under the surveillance of C-arm fluoroscope, four primary guide pins were inserted. The inferior primary guide in the hypothetically symptomatic side was confirmed as the first guide pin. At the end of the first guide pin, the specially designed SAP guide was installed. The secondary guide pin was inserted in the SAP via self-designed SAP guide. Under the protection cannula, part of the superior articular process was removed by oriented SAP resection device, so the working channel was smoothly put through the Kambin's triangle. The endoscope was inserted close to the exiting nerve root. Rotation of the working channel kept the nerve root out of it. RESULTS: Three levels of PE-TLIF were successfully performed in two cadavers. Self-designed SAP guide made the secondary guide pin inserting the SAP accurately. Decompression was adequate and the traversing nerve root was relieved. Three aimed intervertebral levels are implanted with two 7-mm-high PEEK cages and one expandable cage. The expandable cage could be adjusted from 8 mm to 13 mm. Surgical incisions included four 15 mm incisions for percutaneous screw fixation and one 12 mm incision for working channel. There was no nerve injury during the operations. CONCLUSIONS: Our present results showed that the novel minimally invasive surgery PE-TLIF was feasible for the treatment of lumbar degenerative diseases.

17.
Int J Mol Med ; 46(4): 1399-1408, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945389

RESUMO

Atherosclerosis is a disease during which the inside of an artery narrows due to the accumulation of plaque, and vascular smooth muscle cells (VSMCs) are involved in the progression of atherosclerosis. Circular RNAs (circRNAs) have been reported to be involved in the progression of atherosclerosis. However, the role of circ_0010283 in atherosclerosis progression remains unclear. The present study aimed to investigate the functions and the mechanism of circ_0010283 in oxidized low­density lipoprotein (ox­LDL)­induced VSMCs and to identify new potential biomarkers for the treatment of atherosclerosis. Cell viability and migration were examined by 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide and Transwell assays. The relationship between microRNA (miR)­370­3p and circ_0010283 or high mobility group box 1 (HMGB1) was predicated by online software and confirmed by dual­luciferase reporter assay and RNA immunoprecipitation assay. The results of the present study demonstrated that the expression levels of circ_0010283 and HMGB1 were significantly upregulated in ox­LDL­induced VSMCs compared with those in VSMCs without ox­LDL induction, whereas the expression of miR­370­3p was downregulated. Knockdown of circ_0010283 suppressed VSMC viability and migration, as well as the expression of viability­associated proteins cyclin D1 and proliferating cell nuclear antigen, and migration­associated proteins matrix metalloproteinase 2 (MMP2) and MMP9 in ox­LDL­induced VSMCs compared with untreated VSMCs. In addition, miR­370­3p was demonstrated to be a target of circ_0010283 and to target HMGB1; thus, circ_0010283 regulated HMGB1 expression via miR­370­3p. Further experiments indicated that inhibition of miR­370­3p reversed the circ_0010283 silencing­mediated inhibitory effects on VMSC viability and migration. Additionally, the miR­370­3p­mediated suppressive effects on cell viability and migration were rescued by overexpression of HMGB1. In conclusion, circ_0010283 mediated cell viability and migration via a miR­370­3p/HMGB1 axis in ox­LDL­induced VSMCs.

18.
Math Biosci Eng ; 17(4): 3329-3355, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32987532

RESUMO

This study aims to investigate the force transmission characteristics of a multiple-fulcrum supporting platform, and the significance of this paper is to creatively put forward the law of uniform force characteristics of multiple-fulcrum supporting platform with heavy loads and layout reconfiguration methods to realize the law. In this paper, firstly, a force transmission model for the multiple-fulcrum supporting platform has been constructed, the relationship between force transmission characteristics and layout parameters for all fulcrums has been discussed in detail, and the layout law for all fulcrums with the same supporting force has been discovered. Then, layout reconfiguration methods have been proposed to realize the uniform force characteristics of all fulcrums under different types of constraint surfaces (rectangular or square constrained surface, circular constrained surface, and unconstrained surface). Finally, layout reconfiguration methods have been applied to some engineering problems by ADAMS simulation. The simulation results show that the supporting force of all fulcrums in the supporting platform is equal when the layout central point (LCP) of all fulcrums is coincident with the force equivalent point (FEP) of external loads. The results provide theoretical guidance and support for the reconfiguration of multiple-fulcrum supporting platforms that can realize uniform forces among all fulcrums.

19.
J Clin Periodontol ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32935363

RESUMO

AIM: To explore the application of the combined use of baseline salivary biomarkers and clinical parameters in predicting the outcome of scaling and root planing (SRP). MATERIALS AND METHODS: Forty patients with advanced periodontitis were included. Baseline saliva samples were analysed for interleukin-1ß (IL-1ß), matrix metalloproteinase-8 and the loads of Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Tannerella forsythia. After SRP, pocket closure and further attachment loss at 6 months post-treatment were chosen as outcome variables. Models to predict the outcomes were established by generalized estimating equations. RESULTS: The combined use of baseline clinical attachment level (CAL), site location and IL-1ß (area under the curve [AUC] = 0.764) better predicted pocket closure than probing depth (AUC = 0.672), CAL (AUC = 0.679), site location (AUC = 0.654) or IL-1ß (AUC = 0.579) alone. The combination of site location, tooth loss, percentage of deep pockets, detection of A. actinomycetemcomitans and T. forsythia load (AUC = 0.842) better predicted further clinical attachment loss than site location (AUC = 0.715), tooth loss (AUC = 0.530), percentage of deep pockets (AUC = 0.659) or T. forsythia load (AUC = 0.647) alone. CONCLUSION: The combination of baseline salivary biomarkers and clinical parameters better predicted SRP outcomes than each alone. The current study indicates the possible usefulness of salivary biomarkers in addition to tooth-related parameters in predicting SRP outcomes.

20.
Chem Biol Interact ; 331: 109246, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32877639

RESUMO

Colorectal cancer (CRC) represents one of the commonest malignancies around the world. PP9, a natural steroidal saponin, was firstly isolated from the rhizomes of Paris polyphylla var. latifolia. However, the therapeutic effects of PP9 on CRC and the underlying molecular mechanism remain undefined. Here, we demonstrated that treatment with PP9 time- and dose-dependently inhibited HT-29 and HCT116 cells without significantly inhibiting normal NCM460 cells. Furthermore, our results indicated that PP9 effectively induced G2/M phase arrest by upregulating p21 and suppressing cdc25C, Cyclin B1 and cdc2. Meanwhile, PP9 upregulated cleaved Caspase 3, cleaved Caspase 9 and cleaved PARP and Bax, while downregulating Bcl-2 to stimulate cell apoptosis. Mechanistically, PP9-suppressed PI3K/Akt/GSK3ß signaling, while the PI3K inhibitor LY294002 augmented PP9-mediated apoptosis, G2/M arrest and effects on PI3K/Akt/GSK3ß related proteins. Finally, we showed that PP9 (10 mg/kg) significantly reduced tumor growth in nude mouse CRC xenografts, more potently than 5-Fu (20 mg/kg). Jointly, these data firstly demonstrated that PP9 promotes G2/M arrest and apoptotic death in CRC cells through PI3K/Akt/GSK3ß signaling suppression, suggesting that PP9 could be considered a new and promising candidate for CRC therapy.

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