How can urban administrative boundary expansion affect air pollution? Mechanism analysis and empirical test.

As a momentous policy tool for spatial management, urban administrative boundary expansion (UABE) significantly impacts resource reorganization and development modes. However, the environmental effects of UABE are easily ignored. Whether UABE can also impove the environmental quality in addition to its economic effects remains to be answered. To fill this gap, we took the city-county merger policy (CCMP) in China as quasi-experimental evidence and empirically investigated the impacts of CCMP on air pollution based on the difference-in-difference method. The impact mechanisms were also analyzed from a whole-process perspective. The results demonstrate that, apart from expanding the urban scale, UABE can improve urban air quality as well. Further analysis shows that the positive effect is mainly realized by source control and process management, rather than end-of-pipe treatment. Besides, the impacts of UABE on air pollution exhibit obvious spatial heterogeneous characteristics. We also reported that the environmental effects of UABE are largely dependent on governmental control, rather than market factors. According to the results above, flexible administrative boundary adjustment, strict government regulations, and effective market systems are required to realize the dual goals of environmental improvement and space optimization.

Persistence of Antibody and Cellular Immune Responses in Coronavirus Disease 2019 Patients Over Nine Months After Infection.

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.

Effects of irrigation fluid temperature during flexible ureteroscopic holmium laser lithotripsy on postoperative fever and shivering: a randomized controlled trial.

BACKGROUND: Flexible ureteroscopic holmium laser lithotripsy is used to treat urinary tract calculi, but postoperative complications include shivering, fever and infection. To investigate the effects of irrigation fluid temperature on postoperative complications. METHODS: This randomized controlled trial included 120 consecutive patients undergoing flexible ureteroscopic holmium laser lithotripsy at the Urology Department, Suining Central Hospital, Sichuan, China between January 2017 and July 2019. Patients were randomized 1:1:1 into three groups (17 °C, 27 °C or 37 °C). Primary outcome was fever incidence (body temperature > 37.5 °C) within 48 h after surgery. Secondary outcomes included shivering incidence during recovery from anesthesia, white blood cell count (WBC), serum procalcitonin (PCT) and incidence of suspected infection (temperature > 38.5 °C and PCT > 0.5 µg/L). RESULTS: There were 108 patients, (17 °C group, n = 36; 27 °C group, n = 35; 37 °C group, n = 37), received flexible ureteroscopic holmium laser lithotripsy and analyzed. Age, gender distribution, body mass index, ASA grade, stone burden, preoperative creatinine, preoperative core temperature and irrigation fluid volume did not differ significantly between groups. 17 °C, 27 °C and 37 °C groups exhibited significant differences in the incidences of postoperative fever (38.9% vs. 17.1% vs. 13.5%) and shivering (22.2% vs. 5.7% vs. 2.7%) (p < 0.05 for all pairwise comparisons). There was no significant difference of WBC, PCT and incidence of suspected infection in 37 °C or 27 °C group compared with 17 °C group. One case each of flash pulmonary edema and bleeding occurred in 37 °C group. CONCLUSION: Warming the irrigation fluid can reduce the incidence of postoperative fever and shivering, but further studies are needed to determine the optimal temperature. Trial registration The trial was registered at the Chinese Clinical Trials Registry and allocated as ChiCTR2000031683. The trial was registered on 07/04/2020 and this was a retrospective registration.

Isobavachalcone inhibits acute myeloid leukemia: Potential role for ROS-dependent mitochondrial apoptosis and differentiation.

Isobavachalcone (IBC) has been shown to induce apoptosis and differentiation of acute myeloid leukemia (AML) cells. However, the underlying molecular mechanisms are not fully understood. Herein, IBC exhibited significant inhibition on the cell viability, proliferation, and the colony formation ability of AML cells. Moreover, IBC induced mitochondrial apoptosis evidenced by reduced mitochondrial membrane potential, increased Bax level, decreased Bcl-2, Bcl-xL, and Mcl-1 levels, elevated cytochrome c level in the cytosol and increased cleavage of caspase-9, caspase-3, and PARP. Furthermore, IBC obviously promoted the differentiation of AML cells, accompanied by the increase of the phosphorylation of MEK and ERK and the C/EBPα expression as well as the C/EBPß LAP/LIP isoform ratio, which was significantly reversed by U0126, a specific inhibitor of MEK. Notably, IBC enhanced the intracellular ROS level. More importantly, IBC-induced apoptosis and differentiation of HL-60 cells were significantly mitigated by NAC. In addition, IBC also exhibited an obvious anti-AML effect in NOD/SCID mice with the engraftment of HL-60 cells. Together, our study suggests that the ROS-medicated signaling pathway is highly involved in IBC-induced apoptosis and differentiation of AML cells.

DT-13 induced apoptosis and promoted differentiation of acute myeloid leukemia cells by activating AMPK-KLF2 pathway.

Acute myeloid leukemia (AML) is a malignant disease originating from hematopoietic stem cells (HSC). Chemotherapy and/or HSC transplantation is unsatisfactory due to serious side effects, multidrug resistance, and high relapse rate. Thus, alternative strategies are urgently needed to develop more effective therapies. Liriope muscari baily saponins C (DT-13) is a novel compound isolated from Liriope muscari (Decne.) Baily, and exhibited a potent cytotoxicity against several solid tumors. However, the anti-AML activity of DT-13 and the potential mechanisms are still unknown. This study is the first to demonstrate that DT-13 had preferential cytotoxicity against AML cells, and remarkably inhibited proliferation and colony forming ability. Moreover, DT-13 induced the death receptor pathway-dependent apoptosis of HL-60 and Kasumi-1 cells by up-regulating Fas, FasL, DR5 and TRAIL as well as promoted the cleavage of caspase 8, caspase 3 and PARP. Meanwhile, DT-13 induced the differentiation with morphological change related to myeloid differentiation, elevated NBT and α-NAE positive cell rates, differentiation markers CD11b and CD14 as well as level of transcription factors C/EBPα and C/EBPß. RNA-sequencing analysis revealed that KLF2 may be one of the potential targets regulated by DT-13. Further studies indicated that KLF2 played a critical role in DT-13-induced apoptosis and differentiation. Moreover, activation of AMPK-FOXO was proved to be the upstream of KLF2 pathway that contributed to the induction of apoptosis and differentiation by DT-13. Additionally, restoration of KLF2 by DT-13 was highly correlated with the AMPK-related histone acetylation mechanisms. Finally, DT-13 exhibited an obvious anti-AML effect in NOD/SCID mice with the engraftment of HL-60 cells. Our study suggests that DT-13 may serve as a novel agent for AML by AMPL-KLF2-mediated apoptosis and differentiation.

Dual role of Nrf2/HO-1 pathway in Z-ligustilide-induced ferroptosis against AML cells.

BACKGROUND: The scarcity of drugs targeting AML cells poses a significant challenge in AML management. Z-Ligustilide (Z-LIG), a phthalide compound, shows promising pharmacological potential as a candidate for AML therapy. However, its precise selective mechanism remains unclear. PURPOSE: In order to assess the selective inducement effects of Z-LIG on ferroptosis in AML cells and explore the possible involvement of the Nrf2/HO-1 pathway in the regulation of ferroptosis. METHODS: Through in vitro cell proliferation and in vivo tumor growth tests, the evaluation of Z-LIG's anticancer activity was conducted. Ferroptosis was determined by the measurement of ROS and lipid peroxide levels using flow cytometry, as well as the observation of mitochondrial morphology. To analyze the iron-related factors, western blot analysis was employed. The up-regulation of the Nrf2/HO-1 axis was confirmed through various experimental techniques, including CRISPR/Cas9 gene knockout, fluorescent probe staining, and flow cytometry. The efficacy of Z-LIG in inducing ferroptosis was further validated in a xenograft nude mouse model. RESULTS: Our study revealed that Z-LIG specifically triggered lipid peroxidation-driven cell death in AML cells. Z-LIG downregulated the total protein and nuclear entrance levels of IRP2, resulting in upregulation of FTH1 and downregulation of TFR1. Z-LIG significantly increased the susceptibility to ferroptosis by upregulating ACSL4 levels and simultaneously suppressing the activity of GPX4. Notably, the Nrf2/HO-1 pathway displayed a twofold impact in the ferroptosis induced by Z-LIG. Mild activation suppressed ferroptosis, while excessive activation promoted it, mainly driven by ROS-induced labile iron pool (LIP) accumulation in AML cells, which was not observed in normal human cells. Additionally, Nrf2 knockout and HO-1 knockdown reversed iron imbalance and mitochondrial damage induced by Z-LIG in HL-60 cells. Z-LIG effectively inhibited the growth of AML xenografts in mice, and Nrf2 knockout partially weakened its antitumor effect by inhibiting ferroptosis. CONCLUSION: Our study presents biological proof indicating that the selective initiation of ferroptosis in leukemia cells is credited to the excessive activation of the Nrf2/HO-1 pathway triggered by Z-LIG.

How can Chinese metropolises drive global carbon emissions? Based on a nested multi-regional input-output model for China.

Given metropolises' participation in complex regional and global trade networks, they have huge demands for vast carbon-embodied intermediate and final goods. To clarify embodied carbon transfers of metropolises in regional and international trade, a metropolis-centered model was constructed by nesting the World's multi-regional input-output table and China's multi-regional input-output (CMRIO) table. Based on this model, we analyzed the multi-scale impact of two typical Chinese metropolises, namely Beijing and Shanghai, on global carbon emissions. Structural decomposition analysis and social network analysis (SNA) were used to explore the driving factors of consumption-based carbon (CBC) and the roles of metropolises in the carbon networks. Results showed that both Beijing and Shanghai are net embodied carbon consumers, which respectively drove 231.19 and 219.52 Mt global carbon emissions in 2017. These figures were underestimated by 12.54 % and 15.41 % when using the CMRIO. After China's economy entered a new normal, instead of technological progress, structural adjustment became the prominent factor driving the CBC reduction of metropolises. During 2012-2017, the consumption structure optimization reduced 18.87 and 32.48 Mt CBC in Beijing and Shanghai, respectively. Compared with other domestic regions, the CBC of Beijing has continued to increase, whereas that of Shanghai has declined. At the international scale, the combined net carbon emission imported by the two metropolises was 88.43 Mt in 2017, equivalent to 18.09 % of China's total carbon deficit. This indicates that metropolises have become pioneering regions for China to alleviate the carbon deficit in international trade. By using SNA, we further found that both metropolises are crucial carbon consumers in the global carbon network, with strong stability and obvious hub roles. Furthermore, various urban functions and geographical locations form the heterogeneous structural characteristics of CBC in the two metropolises, highlighting the need for different strategies for embodied carbon mitigation in these metropolises.

Spatial effects of air pollutants reduction on CO2 emissions.

The sources of air pollutants and CO2 are basically the same, hence the reduction of air pollutants will affect CO2 emissions. Considering the regional integration of economic development as well as air pollution control, it is necessary to analyze the impact of air pollutants reduction in a region on CO2 emissions in its surrounding regions. Furthermore, as different stages of air pollutants reduction have different effects on CO2 emissions, it is also important to study the heterogeneity of this impact. In this article, we took China as the research case and built a spatial panel model based on the data of 240 cities above the prefecture level from 2005 to 2016 to study the impact of two different stages of air pollutants reduction-front reduction of air pollutants (FRAP) and end-of-pipe treatment of air pollutants (EPAP) on CO2 emissions-and their spatial spillover effects. On this basis, we further modified traditional spatial weight matrix and constructed the matrices of cities in the same and different provinces to discuss the influence of provincial administrative boundaries on the spillover effect between cities. The results show that FRAP affects CO2 emissions mainly through the local synergistic effect, and its spatial spillover effect is not significant. The local effect of EPAP on CO2 emissions is antergic, and the spatial spillover effect is significant. The increase of a city's EPAP will increase the CO2 emissions in surrounding regions. Besides, provincial boundaries weaken the spatial spillover effects of FRAP and EPAP on CO2 emissions in prefecture-level cities. There is a significant spatial spillover effect between cities in the same province, but the spillover effect does not exist for cities in different provinces nearby.

Z-ligustilide preferentially caused mitochondrial dysfunction in AML HL-60 cells by activating nuclear receptors NUR77 and NOR1.

BACKGROUND: Nuclear receptors NUR77 and NOR1 were identified as critical targets in acute myeloid leukemia (AML) therapy. Previously, we showed that Z-ligustilide (Z-LIG) selectively targeted AML by restoring NUR77 and NOR1. However, its downstream mechanisms are yet to be elucidated. METHODS: SRB staining assay was used to measure cell viability. Cell apoptosis, mitochondrial membrane potential and mitochondrial reactive oxygen species were analyzed using flow cytometry. The potential targets of Z-LIG in AML HL-60 cells were evaluated by RNA sequencing. Changes in RNA levels were measured using quantitative RT-qPCR and western blot analysis was used to detect the expression of proteins. RESULTS: Z-LIG preferentially induced mitochondrial dysfunction in HL-60 cells compared with 293T cells. Furthermore, RNA sequencing revealed that mitochondrial transcription and translation might be potential Z-LIG targets inhibiting HL-60 cells. NUR77/NOR1 overexpression significantly reduced the mitochondrial ATP and mitochondrial membrane potential and increased mitochondrial reactive oxygen species in HL-60 cells but not in 293T cells. Moreover, Z-LIG induced mitochondrial dysfunction by restoring NUR77 and NOR1 in HL-60 cells. Compared with HL-60 cells, the apoptosis-inducing activities of NUR77/NOR1 and Z-LIG were significantly reduced in HL-60 ρ0 cells depleted in mitochondrial DNA (mt-DNA). Moreover, NUR77/NOR1 and Z-LIG downregulated mitochondrial transcription and translation related proteins in HL-60 cells. Notably, Z-LIG remarkably reduced mitochondrial ATP in primary AML cells and showed anti-AML activity in mouse models of human AML. CONCLUSIONS: Collectively, our findings suggested that Z-LIG selectively induces mitochondrial dysfunction in AML HL-60 cells by restoring NUR77 and NOR1, a process associated with interference in mtDNA transcription.

Motion and Load Analysis of the Flexible Platform Based on Noncontact Processing.

In this paper, we explore the applicability of the positioning stage based on flexible hinges for noncontact processing. According to the actual application of the positioning stage, Hooke's law, the Euler-Bernoulli beam theory, and the geometric relationship of the structure are applied to analyze the coupled displacement in the movement of the positioning stage and the changes in the performance of the positioning stage caused by external loads. The coupled-displacement matrix and the external-load matrix obtained from the analysis are substituted into the ideal-displacement expression of the positioning stage to obtain the displacement expression of the platform in noncontact machining. The platform trajectory obtained by the referenced curve is analyzed. In addition, the coupled displacement in the X- and Y-directions and the coupled displacement caused by the external load in the Z-direction are nanoscales and about one-thousandth of the output displacement, which meets the requirement of tracking accuracy for micron-level machining. Finally, we use finite element analysis (FEA) and experiments to prove the correctness of the theoretical analysis.

Dual effects of technology change: How does water technological progress affect China's water consumption?

Water technological progress contributes a lot to water conservation. Most studies have overestimated its contribution by ignoring its scale effect on economic growth, leading to the increase in water consumption. To quantify the trade-off of water technological progress, we combine the macroeconomic model with the environmental model to analyze both the scale effect and the intensity effect of water technological progress. Results show that the intensity effect has reduced China's water consumption by 612.256 × 109 m3 from 2003 to 2020, while the scale effect increases China's water consumption by 189.911 × 109 m3. The contribution of technological progress varies among regions in China. The industrial structure effect inhibits water consumption, second to the water-saving effect of water technological progress. The input effect increases water consumption owing to the particularly striking promotion of the effect of capital input. Some policy recommendations are given to mitigate the trade-off of water technological progress and regional disparity.

Retroperitoneal tumor finally diagnosed as a bronchogenic cyst: A case report and review of literature.

BACKGROUND: Retroperitoneal bronchogenic cyst (RBC) is an extremely rare developmental abnormality. Most are benign tumors but malignant transformation is possible. Because of their anatomical position, RBCs are easily misdiagnosed as adrenal or pancreatic solid tumors on radiological evaluation. Here, we report a case of RBC, review the literature, and summarize some important features. CASE SUMMARY: A 49-year-old woman was incidentally found to have a retroperitoneal tumor during a physical examination. Enhanced computed tomography and laboratory evaluations, including routine blood examination, blood biochemistry, 24-h urine 17 ketones, 17 hydroxyls, adrenocortical hormone, serum potassium concentration, serum amylase, lipase, and epithelial tumor markers, revealed a moderate density, 54 mm × 40 mm mass with a clear boundary near the left adrenal gland. The were no abnormalities in the blood and urine values. Because the patient had a history of hypertension and the location of the mass was adjacent to the adrenal gland, it was initially diagnosed as a left adrenal tumor and was resected by retroperitoneal laparoscopy. However, the pathological examination after surgery confirmed it to be a bronchogenic cyst. CONCLUSION: Retroperitoneal laparoscopic surgery can be prioritized for symptomatic RBC patients. Conservative treatment is feasible for selected patients.

Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants.

BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.

Celecoxib and Afatinib synergistic enhance radiotherapy sensitivity on human non-small cell lung cancer A549 cells.

PURPOSE: Radioresistance is highly correlated with radiotherapy failure in clinical cancer treatment. In the current study, we sought to examine the efficacy of Celecoxib and Afatinib co-treatment as radiosensitizers in the management of non-small cell lung cancer (NSCLC) A549 cells. MATERIALS AND METHODS: Generally, A549 cells were cultured with the treatment of Celecoxib and/or Afatinib for 24 h. Then, the cells were exposed to irradiation at 2 Gy/min for 1 min. After the end of treatment, cell viability, clonogenic survival, apoptosis and Prostaglandin E2 (PGE2) Elisa assays were performed. Transcriptional levels of Cyclooxygenase-2 (COX-2) affected by Celecoxib and/or Afatinib were measured by RT-qPCR. Posttranscriptional level of epidermal growth factor receptor (EGFR)-related gene was measured by Western blotting analysis. RESULTS: Here, we, for the first time, reported that the co-treatment of Celecoxib and Afatinib regulates the resistance of NSCLC A549 cells to radiation. The co-treatment of Celecoxib and Afatinib sensitized radiotherapy through the radiation-induced loss of cell viability and colony formation, as well as apoptosis. Mechanistically, Celecoxib and Afatinib-treated cells showed the inhibition of COX-2 and EGFR expression, which may be responsible for the A549 cells' increased resistance to radiation. CONCLUSION: Our results suggested that Celecoxib and Afatinib regulate cell sensitivity to apoptosis, and thus modulate the resistance of NSCLC to radiation.

Z-Ligustilide Selectively Targets AML by Restoring Nuclear Receptors Nur77 and NOR-1-mediated Apoptosis and Differentiation.

BACKGROUND: Acute myeloid leukemia (AML) is a devastating hematologic malignancy with a high mortality. The nuclear receptors Nur77 and NOR-1 are commonly downregulated in human AML blasts and have emerged as key therapeutic targets for AML. METHODS: This study aimed to identify Z-ligustilide (Z-LIG), the main phthalide of Rhizoma Chuanxiong, as a potential agent that can selectively target AML. The anti-AML activity of Z-LIG was evaluated in vitro and in vivo, and the effect and underlying mechanisms of Z-LIG on the restoration of Nur77 and NOR-1 was determined. Moreover, the role of Nur77 and NOR-1 in the regulation of Z-LIG-induced apoptosis and differentiation of AML cells was explored. RESULTS: Z-LIG preferentially inhibited the viability of human AML cells, as well as suppressed the proliferation and colony formation ability. Notably, a concentration-dependent dual effect of Z-LIG was observed in AML cells: inducing apoptosis at relatively high concentrations (25 µM to 100 µM) and promoting differentiation at relatively low concentrations (10 µM and 25 µM). Importantly, Z-LIG restored Nur77 and NOR-1 expression in AML cells by increasing Ace-H3 (lys9/14) enrichment in their promoters. Meanwhile, Z-LIG enhanced the recruitment of p300 and reduced the recruitment of HDAC1, HDAC4/5/7, and MTA1 in the Nur77 promoter and enhanced the recruitment of p-CREB and reduced HDAC1 and HDAC3 in the NOR-1 promoter. Furthermore, Z-LIG-induced apoptosis was shown to be correlated with the mitochondria localization of Nur77/NOR-1 and subsequent Bcl-2 conformational change, converting Bcl-2 from a cyto-protective phenotype into a cyto-destructive phenotype. Z-LIG-promoted differentiation was found to be related to Nur77/NOR-1-mediated myeloid differentiation-associated transcription factors Jun B, c-Jun, and C/EBPß. Finally, silencing of Nur77 and NOR-1 attenuated anti-AML activity of Z-LIG in NOD/SCID mice. CONCLUSIONS: Our study suggests that Z-LIG may serve as a novel bifunctional agent for AML by restoring Nur77/NOR-1-mediated apoptosis and differentiation.

Dynamic Analysis and Experiment of 6-DOF Compliant Platform Based on Bridge-Type Amplifier.

In this paper, we establish a dynamic model of a six-degrees-of-freedom (6-DOF) compliant positioning platform based on bridge-type amplifiers. Based on the elastic beam theory and energy relationship, we derived the bridge-type amplifier's dynamic model using the Lagrange equation. Then, we established a dynamic model of the compliant platform based on the equivalent mass and equivalent stiffness of the bridge-type amplifier, and the analysis formula of the natural frequency was derived. Finally, the analytical models of natural frequencies of the bridge-type amplifier and the compliant platforms were verified using the finite element analysis (FEA) method. Through modal experiments, the damping ratio and natural frequency were identified. Step response experiments in the X/Y direction and Z direction were performed. The phenomenon that the experimental results appeared to match the theoretical calculations indicates that the dynamic model was accurate.

Cantharidin Induces Apoptosis and Promotes Differentiation of AML Cells Through Nuclear Receptor Nur77-Mediated Signaling Pathway.

BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by uncontrolled proliferation and accumulation of myeloblasts in the bone marrow (BM), blood, and other organs. The nuclear receptors Nur77 is a common feature in leukemic blasts and has emerged as a key therapeutic target for AML. Cantharidin (CTD), a main medicinal component of Mylabris (blister beetle), exerts an anticancer effect in multiple types of cancer cells. PURPOSE: This study aims to characterize the anti-AML activity of CTD in vitro and in vivo and explore the potential role of Nur77 signaling pathway. STUDY DESIGN/METHODS: The inhibition of CTD on cell viability was performed in different AML cells, and then the inhibition of CTD on proliferation and colony formation was detected in HL-60 cells. Induction of apoptosis and promotion of differentiation by CTD were further determined. Then, the potential role of Nur77 signaling pathway was assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice. RESULTS: In our study, CTD exhibited potent inhibition on cell viability and colony formation ability of AML cells. Moreover, CTD significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. Meanwhile, CTD promoted the cleavage of caspases 8, 3 and PARP in HL-60 cells. Furthermore, CTD obviously suppressed the proliferation and induced the cell cycle arrest of HL-60 cells at G2/M phase. Meanwhile, CTD effectively promoted the differentiation of HL-60 cells. Notably, CTD transiently induced the expression of Nur77 protein. Interestingly, CTD promoted Nur77 translocation from the nucleus to the mitochondria and enhanced the interaction between Nur77 and Bcl-2, resulting in the exposure of the BH3 domain of Bcl-2, which is critical for the conversion of Bcl-2 from an antiapoptotic to a proapoptotic protein. Importantly, silencing of Nur77 attenuated CTD-induced apoptosis, reversed CTD-mediated cell cycle arrest and differentiation of HL-60 cells. Additionally, CTD also exhibited an antileukemic effect in NOD/SCID mice with the injection of HL-60 cells into the tail vein. CONCLUSIONS: Our studies suggest that Nur77-mediated signaling pathway may play a critical role in the induction of apoptosis and promotion of differentiation by CTD on AML cells.

Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression.

The current study aimed to identify the radiosensitizing effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in combination with radiotherapy in non-small-cell lung cancer (NSCLC) cells. The combination of celecoxib potentiated radiation-induced apoptosis; however, no changes in cell cycle distribution and number of phosphorylated histone H2AX foci were detected, indicating a DNA damage-independent mechanism. In an in vivo mouse model, the tumor size was significantly decreased in the group combining celecoxib with radiation compared with the radiation only group. Phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), as well as expression of COX-2 were significantly downregulated in cells treated with the combination of celecoxib and radiation compared with the radiation only group. The result indicated that celecoxib exhibits radiosensitizing effects through COX-2 and Akt/mTOR-dependent mechanisms. Induction the Akt/mTOR signaling pathway promotes radioresistance in various cancers, including NSCLC. Therefore, the current study suggested the therapeutic potential of combination therapy of celecoxib and radiation in the prevention of radioresistance.

[Application of superparamagnetic iron oxide labeled antisense oligodeoxynucleotide probe in cellular magnetic resonance imaging].

OBJECTIVE: To prepare the superparamagnetic iron oxide (SPIO)-labeled antisense oligodeoxynucleotide (ASODN) probe and evaluate the application of this probe in cellular magnetic resonance imaging (MRI). METHODS: We prepared the SPIO-labeled ASODN probe using chemical cross linking method to conjugate SPIO to ASODN, detected its configuration by atomic force microscopy, determined the conjugating rate and biology activation by high performance liquid chromatography, and detected the stability by polyacrylamide gel electrophoresis. After that, we transfected the SK-Br3 oncocytes which had over-expression of the c-erbB2 oncogene by this probes, observed the intracellular iron distribution by optical microscope, measured iron content by atomic absorption spectroscopy, and observed the signal change by MRI. RESULTS: Atomic force microscope showed that the SPIO-labeled ASODN probe was mostly spherical and well-distributed, with a diameter of 25-40 nm and a conjugating rate of 100%. This probe had inhered biological activity and stability. In addition, light microscopy revealed an intracellular uptake of iron oxides in the transfected SK-Br3 oncocyte, and the iron content of the group of transfected SK-Br3 oncocytes was significantly higher than those of other contrast groups (all P < 0.01). MRI showed that transfected SK-Br3 oncocyte had the lowest signal among all other cells (all P < 0.05). CONCLUSIONS: We prepared the SPIO-labeled ASODN probe successfully. It can effectively transfect SK-Br3 oncocyte and enter SK-Br3 oncocyte, and thus reduce the signal intension in MRI.