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Li-rich Mn-based materials provide higher capacity than commercial NCM layered materials due to the synergistic redox effect of cations and anions. However, lattice straining and structural collapse caused by the irreversible oxygen release at high voltage range during cycling, which results in severe capacity and voltage decay. Herein, a synergistic strategy of surface-induced spinel structure and F doping is provided to improve the structural stability. The surface spinel structure helps to reduce the structural collapse caused by electrolyte corrosion on the cathode and effectively inhibits voltage decay resulted from structural evolution. The stronger Mn-F bonds are formed by F doping to inhibit migration of transition metal (TM) and induce the uniform deposition of LiF to form the thinner and more stable CEI on the cathode. Accordingly, the designed cathode (LMNO-NF) shows remarkable cycling performance with the capacity retention of 86.68 ​% and voltage retention of 96.6 ​% for 200 cycles at 1C, higher than pristine material (68.76 ​% and 85.75 ​%). Therefore, this simple dual-modification strategy of one-step synthesis is promising for solving the structural evolution and voltage decay of Li-rich Mn-based cathode materials effectively, achieving further commercialization. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the public health issue worldwide. Paclitaxel is a first-line chemotherapy drug for ovarian cancer, but paclitaxel resistance weakens the therapeutic effect. Metformin (Met) improved the paclitaxel sensitivity in a mouse model of ovarian cancer. However, the mechanism of Met on paclitaxel sensitivity is still unclear in ovarian cancer. Materials and Methods: Cell viability, apoptosis, migration, and invasion were measured by Cell Counting Kit-8 (CCK8), flow cytometry, and transwell assays severally. The expression of long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) and microRNA-3127-5p (miR-3127-5p) were detected by real-time quantitative polymerase chain reaction. The protein levels of poly (ADP-ribose) polymerase, microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, and Beclin 1 were examined by Western blot assay. RNA immunoprecipitation assay detected the relationship between SNHG7 and miR-3127-5p. Then, the binding correlation between SNHG7 and miR-3127-5p was predicted by starBase and verified by the dual-luciferase reporter. The effects of Met and SNHG7 on tumor growth were tested in ovarian cancer mice model. Results: Met inhibited cell viability, migration, invasion, SNHG7 level, and autophagy and promoted apoptosis in paclitaxel-resistant ovarian cancer cells. Moreover, Met partly reversed SNHG7-mediated paclitaxel sensitivity and autophagy in ovarian cancer cells. SNHG7 directly bound to miR-3127-5p. Met abolished the promoting effect of SNHG7 overexpression on tumor growth and autophagy in vivo. Conclusion: The authors' findings indicated that Met expedited paclitaxel sensitivity by regulating SNHG7/miR-3127-5p-mediated autophagy in ovarian cancer cells. [ABSTRACT FROM AUTHOR]

• The equivalent method from bolted connections to spectral problem is presented. • The integrable system equivalent to a bolted connection is established. • A novel mathematical model is proposed for evaluating bolt preload. • The proposed model considers the geometric and physical parameters. • The preload is especially sensitive to the geometric parameters of connected parts. Accurate evaluation of preload in system with double-bolted connections is critical for the service performance of engineering structures or equipment. However, the theoretical framework for assessing preload is imperfect. An equivalent approach from the tightening process of double-bolted joints to second-order spectral problem of the energy-dependent potential is firstly established. This paper proposes a novel nonlinear model of bolt preload considering physical and geometric parameters by proving the completely integrability of systems used bolted connections. The experimental device for hmeasuring displacement and bolt preload was developed to verify the accuracy of proposed model. Results show that the maximum relative error is not more than 3%. Finally, the influences of elastic modulus, density, holes spacing, and height on preload are analyzed. [ABSTRACT FROM AUTHOR]

[Display omitted] • The doping of Al ions has a positive effect on the structural stability of the material. • The improved cathode shows an outstanding cycling stability (81.9% after 200 cycles) and rate performance (183 mAh·g−1 at 10C). • The enhanced structural stability of the material promotes improved material properties. Ni-rich layered oxides materials, such as LiNi x Co y O 2 (NC, x ≥ 0.8, x + y = 1), are one of the most considerable potential materials in lithium-ion batteries (LIBs). However, what with the performance degradation and structural collapse upon prolonged cycling, studies are still ongoing to enhance their performance. Among the available research methods, doping has been shown to enhance the cycle life of materials by stabilizing the layered structure. Herein, both the electrochemical properties and the structural stability of the Ni-rich (LiNi 0.98 Co 0.02 O 2) materials are significantly improved via the doping of Al. This can be attributed to the Al-doped Ni-rich cathode maintaining a wider lithium layer spacing at high charge states without collapse, facilitating the de-intercalation/intercalation of Li+. In addition, the stronger Al-O bonded Al can act to stabilize the structure to retard capacity/voltage decay. Electrochemical testing results indicate that the Al-doped Ni-rich materials exhibit specific capacities of 235 mAh g−1 at 0.1 C (1 C = 180 mA g−1), 202 mAh g−1 at 1 C, and the capacity retention rate is 80.02% after 200 cycles. Moreover, the capacity of 183 mAh g−1 at a rate of 10 C illustrates its remarkable rate capability. The Al doping inhibits the phase transformation and expands the lattice spacing, which significantly improves the electrochemical performance of LiNi 0.98 Co 0.02 O 2. Therefore, this paper focuses on the role of Al doping on the structure of layered cathode materials and pioneers the way for enhancing the structural stability of layered cathode materials for high energy LIBs. [ABSTRACT FROM AUTHOR]

Layered Li-rich (LLR) oxide electrodes are expected to be strong contenders for next-generation lithium-ion battery materials. However, irreversible anionic redox reactions during cycling lead to oxygen loss and capacity and voltage fading. Here, One-step synthesis strategy with Fe(NH 4) 2 ·(SO 4) 2 has been proposed to achieve Fe-ion replacement and induce the generation of oxygen vacancies. Oxygen vacancies can inhibit the irreversible O release and alleviate the corrosion of the surface and interior of the material by electrolysis. The doping of Fe ions can further stabilize the structure and improve the cycle stability of the material. Owing to this "one stone two birds" modification strategy, the modified materials exhibit significantly reduced interfacial impedance and enhanced cycling stability. Therefore, compared 183.9 mAh g−1 and 69.78% for the original materials, the discharge-specific capacities of 223.1 mAh g−1 at 1 C (1 C = 250 mA g−1) with 81.8% capacity retentions after 300 cycles for the modified materials. Furthermore, the voltage decay is significantly suppressed to 0.002 V/cycle. This work provides a novel idea for manipulating structural stability to enhance the electrochemical performance of Li-rich materials. [Display omitted] • The One-step synthesis strategy is beneficial to improve the homogeneity of the reaction between particles. • The doping of Fe ions has a positive effect on the structural stability of the material. • The improved cathode shows an outstanding cycling stability (81.8% after 300 cycles) and relieved voltage decay (0.6086 V after 300 cycles). [ABSTRACT FROM AUTHOR]

The clamping force relaxation of bolted joints caused by contact creep at ambient temperature has a significant impact on the service performance of offshore structures, which may increase their vulnerability to additional non-typical loads. Maxwell and Kelvin architectures are introduced to analyze the creep displacement of rough surfaces in contact. Subsequently, a theoretical model is established to characterize the functional relationship between contact creep and clamping force relaxation. The model parameters are obtained from a compression creep experiment. An experimental device is developed to validate the proposed model. The experimental results show a good agreement with theoretical calculations. In addition, the influences of bolt preload and surface topography on the clamping force relaxation are investigated quantitatively, and find that the clamping force relaxation is proportional to the surface roughness. Thus, controlling surface topography and bolt preload could be an effective way to improve performance of bolted joints for steel structures. • Contact creep displacement at ambient-temperature creep is analyzed. • The functional relationship between creep and relaxation is characterized. • A novel experimental method is proposed to obtain the model parameters. • The clamping force relaxation decreases with the increase of surface roughness. [ABSTRACT FROM AUTHOR]

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0–1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2–4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1–14, 29–42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7–27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0–21.9 months) and 20.5 months (95% CI 11.8–27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33–NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77–26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27–1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72–2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula. [ABSTRACT FROM AUTHOR]

Background: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. Methods: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4–6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. Discussion: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI. [ABSTRACT FROM AUTHOR]

Preload relaxation, caused by elastic interaction between tightened bolts, is one of the major reasons for non-uniformity of pretension force. But how to accurately assess the residual tension of a bolt is still extremely difficult. This paper considers two types of multiple bolted joint and six kinds of tightening sequence. Based on the deformation compatibility equation and elastic interaction stiffness, the generalized mathematical model for evaluating residual preload of bolts is established. Certain model parameters are obtained through numerical simulation. To analyze the influence of initial tightening torque, spacing between bolt holes, bolt material and gasket material on the elastic interaction stiffness, experimental devices and test procedures are developed. Furtherly, preload relaxation models are validated by tests conducted on six types of multi-bolted joint with the same surface roughness. Results of the proposed mathematical model of pretension force show a good consistency with those of corresponding experiment. • A mathematical model for estimating preload relaxation of bolted joint subjected to elastic interaction was established. • The elastic interaction stiffness between bolts was analyzed based on developed Experimental devices and test procedures. • The proposed mathematical model of pretension force shows a good consistency with the corresponding experiment. [ABSTRACT FROM AUTHOR]

A self-compacting engineering to obtain Li 1.15 Mn 0.56 Ni 0.16 Co 0.08 O 2 materials with high compactness and outstanding electrochemical profile. [Display omitted] • The self-compacting engineering improves the compactness of the material and stabilizes the overall structure. • The co-doping of cation (Mg) and anion (Cl) inhibits the transition from lamellar to spinel phase. • The improved cathode shows an outstanding cycling stability (80.9 % after 300 cycles) and relieved voltage decay (0.5416 V after 300 cycles). Lithium-rich layered oxides (LLOs) are emerging as powerful competitors for Li-ion battery materials with high reversible capacity (≈ 300 mAh/g) and high energy density. Nevertheless, these oxides are prone to irreversible removal of oxygen and Li from the lattice during cycling, which in turn leads to notable capacity and voltage decay. Herein, we propose a self-compacting engineering to improve the compactness and electrochemical performance of LLOs materials. The results of particle cross-section characterization show that the particle interior of the modified LLOs is more compact than the raw LLOs. Electrochemical testing results indicate that the designed LLOs cathode exhibits discharge-specific capacities of 296 mAh/g at 0.1C as well as 230 mAh/g at 1C with 80.9 % capacity retentions after 300 cycles. Besides, effective suppression is achieved especially at 200 mA g−1 with a voltage decay of 0.0018 V/cycle. The increased structural density can inhibit the entry of electrolyte into the interior of the particles and ease the collapse of the internal structure, and the co-doping of cation (Mg) and anion (Cl) inhibits the transition from lamellar to spinel phase, which significantly improves the electrochemical performance of LLOs. The self-compacting engineering paves a broad path in manipulating structural stability to enhance LLOs performance for high-energy LIBs. [ABSTRACT FROM AUTHOR]

Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of TP53 and KRAS, KIF5B-RET fusion, copy number gains of PD-L1 and PD-L2, and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of EGFR and MDM2 and loss of PTPRD were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Recent developments in adipose-derived stromal/stem cell (ADSC) biology provide new hopes for tissue engineering and regeneration medicine. Due to their pluripotent activity, paracrine activity, and immunomodulatory function, ADSCs have been widely administrated and exhibited significant therapeutic effects in the treatment for autoimmune disorders, neurodegenerative diseases, and ischemic conditions both in animals and human clinical trials. Cell-assisted lipotransfer (CAL) based on ADSCs has emerged as a promising cell therapy technology and significantly improved the fat graft retention. Initially applied for cosmetic breast and facial enhancement, CAL has found a potential use for breast reconstruction in breast cancer patients. However, more challenges emerge related to CAL including lack of a standardized surgical procedure, the controversy in the effectiveness of CAL, and the potential oncogenic risk of ADSCs in cancer patients. In this review, we summarized the latest research and intended to give an outline involving the biological characteristics of ADSCs as well as the preclinical and clinical application of ADSCs. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated.Methods: Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3' untranslated region (3'UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues.Results: Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo.Conclusions: Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic. [ABSTRACT FROM AUTHOR]

It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, we present an integrated overview of these recent literatures charging LSD1 with unforeseen functions to re-evaluate and summarize its non-catalytic biological roles beyond the current understanding of its demethylase activity. Given LSD1 is reported to be ubiquitously overexpressed in a variety of tumors, it has been generally considered as an innovative target for cancer therapy. We anticipate that these non-canonical functions of LSD1 will arouse the consideration that extending the LSD1-based drug discovery to targeting LSD1 protein interactions non-catalytically, not only its demethylase activity, may be a novel strategy for cancer prevention. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) is a commonly used drug for gallbladder cancer (GBC) chemotherapy. However, resistance to CDDP treatment results in relapse. Therefore, there is a need for the development of more effective treatment strategies to overcome chemoresistance. Dual-specificity phosphatase 1 (DUSP1) was reported to be involved in the resistance of a number of chemotherapeutic agents and was revealed to be highly expressed in CDDP-resistant GBC cells and CDDP-treated tumor types compared with normal cells or tissues in the present study. DUSP1 was revealed to inhibit the cytotoxicity of CDDP in two GBC cell lines, SGC996 and GBC-SD. P38 mitogen-activated protein kinases may be involved in the mechanism of chemoresistance. Furthermore, the number of DNA double-strand breaks in SGC996 OE cells was reduced compared with SGC996 vector cells indicating DUSP1 may attenuate the chemotherapeutic efficiency. Due to its potency against CDDP treatment, DUSP1 may be a promising target to overcome chemoresistance in GBC therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in patients with esophageal squamous cell carcinoma (ESCC) in Chinese population.Patients and Methods: Patients with ESCC, who received SIB-IMRT from September 2011 to January 2013 were retrospectively analyzed. The SIB-IMRT plans were designed to deliver primary gross tumor volume at 60-64.4 Gy in 28-30 fractions, and planning target volume at 50.4-56 Gy in 28-30 fractions. Treatment-related toxicities were estimated based on Common Terminology Criteria for Adverse Events version 4.0, and tumor response after the treatment was estimated according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS), locoregional progression-free survival (LPFS), and progression-free survival (PFS) were estimated with Kaplan-Meier.Results: All patients completed definitive radiotherapy, 54 (78.3%) received combined chemotherapy, of which 31 (44.9%) were concurrent chemoradiotherapy and 23 (33.3%) were sequential chemotherapy. The objective response rate is 82.6% (56/69), with complete response 11 (15.9%), partial response 45 (65.2%), stable disease 8 (11.6%), and progressive disease 5 (7.2%). The 1-, 2- and 3-year LPFS was 74.4%, 57.8%, and 55.6%, respectively. The 1-, 2- and 3-year PFS was 62.3%, 41.0%, and 34.2%, respectively, and the 1-, 2-, and 3-year OS was 73.8%, 57.4%, and 41.0%, respectively, with a median OS of 27.1 months (4.5-54.9 m). For those who received concurrent chemotherapy, the 1-, 2-, and 3-year OS was 75.9%, 69.0%, and 55.2%, respectively, better than those who had sequential chemotherapy or radiotherapy alone (χ2 = 3.115, P = 0.078). Radiation esophagitis occurred in 63.8% and 14.5% with Grade 2 and 3, respectively. No patients occurred ≥ Grade 3 radiation pneumonia.Conclusions: It is safe and effective using SIB-IMRT technology to treat patients with ESCC. More prospective clinical studies should be needed. [ABSTRACT FROM AUTHOR]

MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and a probable suppressor of diverse cancer cells; however, this miRNA's expression and anti-tumor mechanism in esophageal squamous cancer cells (ESCC) remains unclear. We explored these questions in three human ESCC lines, KYSE-450, KYSE-410, and ECa-109, with wild-type p53 and mutant p53 backgrounds. Through a specific stem-loop RT primer for miR-34a, we examined the relevant expression level of miR-34a in these three cell lines using real-time reverse transcription PCR (qRT-PCR). We found that the expression level of miR-34a induced by the DNA damage agent adrmycin (ADR) was both p53- and time-dependent. Following incubation with miR-34a, cellular growth inhibition was exhibited differently in the three cell lines harbored with different p53 backgrounds. Furthermore, the MTT assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to examine senescence-like phenotypes induced by miR-34a. Mechanistic investigation suggested that the down-regulation of Sirtuin1 (SIRT1) and up-regulation of p53/p21 contributed to the anti-tumor mechanism of miR-34a in wild-type p53 ECa-109 cells, while neither of the apoptosis-related proteins PARP and caspase-3 caused significant changes. In summary, our findings indicated that the intrinsic expression of miR-34a was relatively low and was expressed differently among different p53 backgrounds and ADR treatment times. The anti-tumor effect of miR-34a was primarily dependent on the regulation of SIRT1 and p53/p21 protein, not apoptosis-associated proteins. [ABSTRACT FROM AUTHOR]

• Based on simulation, a new method for analyzing self-loosening of bolts is proposed. • The simulation with helix angle thread is adopted to improve the analysis accuracy. • The self-loosening behavior of bolt can be caused by elastic slip. • Elastic-plastic deformation is the main factor of bolt self-loosening behavior. • Tightening torque and friction coefficient also affect the self-loosening behavior. The self-loosening of high strength bolt caused by vibration has been widely studied. However, the short-term self-loosening behavior of the high strength bolt when it is not subject to an external load has not received attention. This behavior will also lead the bolt preload to attenuate. Since the theoretical analysis of self-loosening behavior is difficult, this paper uses the finite element method to construct an accurate three-dimensions model with thread lift angle for numerical analysis. A new method is proposed to analyze the self-loosening behavior. The self-loosening behavior caused by the elasticity and plasticity of the bolted joint at different deformation periods is compared and analyzed. Besides, the evolution of the self-loosening behavior under different conditions is explored. The analysis results show that the torsional deformation of the thread leads to the relative slip of the internal and external threads. This results in the self-loosening of the thread in the elastic condition. In the elastic–plastic deformation condition, the self-loosening behavior is caused by the relative slip of the internal and external threads and plastic deformation. The weight of plastic deformation is greater. In addition, this behavior has the characteristics of increasing with increased tightening torque and decreasing with increased friction coefficient. [ABSTRACT FROM AUTHOR]

Myopia is the most common form of refractive eye disease, and the prevalence is increasing rapidly worldwide. However, the key metabolic alterations in individuals with high myopia are not understood clearly, and serum biomarkers remain to be determined. The objectives of this study were to identify serum biomarkers and investigate the metabolic alterations of myopia. The serum metabolomics profiling was investigated on 30 high myopia cases and 30 controls (without myopia) using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), and an independent additional cohort including 20 cases and 19 controls were investigated to validate potential metabolite candidates for biomarkers. According to the metabolic differences, the myopia patients and controls could be divided into different clusters and nine metabolites were found to be closely correlated with myopia. In the cohort of validation, eight metabolites were confirmed. Metabolic pathway analyses of these metabolites of high myopia involved abnormal phospholipid, diacylglycerol, amino acid, and vitamin metabolism, which were closely correlated with oxidative stress and inflammation. Multiple logistic regression analyses showed that γ-glutamyltyrosine and 12-oxo-20-trihydroxy-leukotriene B4 were potential biomarkers of myopia with a combined high sensitivity (97%), specificity (90%), and area under the curve value (0.983). These findings may contribute to an understanding of the pathophysiological changes and pathogenesis of myopia, and provide novel insight into the early prevention and control of high myopia. • A two-stage study was conducted using metabolomics analyses of high myopia. • Eight metabolites were found correlated with myopia in both discovery and validation cohorts. • Myopia patients had abnormal phospholipid, diacylglycerol, amino acid, and vitamin metabolism. • The γ-glutamyltyrosine and 12-oxo-20-trihydroxy-leukotriene B4 were potential myopia biomarkers. • These findings may provide a novel insight into the early prevention and control of high myopia. [ABSTRACT FROM AUTHOR]