Cargo-eliminated osteosarcoma-derived small extracellular vesicles mediating competitive cellular uptake for inhibiting pulmonary metastasis of osteosarcoma.

Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs' function by CE-sEVs.

Sensitive electrochemical biosensor for rapid detection of sEV-miRNA based turbo-like localized catalytic hairpin assembly.

Small extracellular vesicle-associated microRNAs (sEV-miRNAs) have emerged as critical biomarkers for cancer diagnosis, yet the rapid detection of these low-abundance molecules in clinical samples remains a formidable challenge. Herein, a simple turbo-like localized catalytic hairpin assembly (TL-CHA) was proposed for sEV-miR-1246 measurement. This electrochemical sensor achieves dual localization through the ingeniously use of AuNPs and DNA nanowires, which provides rich sites for CHA cascade amplification, significantly enhancing the effective reaction and amplify the detection response. Leveraging this innovative design, this biosensor demonstrated the ability to detect sEV-miRNA at concentrations as low as 5.24 aM in a time frame of 30 min. The precision of the measurements was validated through reverse transcription quantitative polymerase chain reaction. Furthermore, the sensor was used for analyzing plasma samples from gastric cancer patients yielded AUC values of 0.973 for all stages and 0.945 for early stages. This demonstrates the sensor's robust performance in both the staging diagnosis and early screening of gastric cancer. Therefore, this platform has great potential for the clinical cancer diagnosis.

Meta-Quantitative Trait Loci Analysis and Candidate Gene Mining for Drought Tolerance-Associated Traits in Maize (Zea mays L.).

Drought is one of the major abiotic stresses with a severe negative impact on maize production globally. Understanding the genetic architecture of drought tolerance in maize is a crucial step towards the breeding of drought-tolerant varieties and a targeted exploitation of genetic resources. In this study, 511 quantitative trait loci (QTL) related to grain yield components, flowering time, and plant morphology under drought conditions, as well as drought tolerance index were collected from 27 published studies and then projected on the IBM2 2008 Neighbors reference map for meta-analysis. In total, 83 meta-QTL (MQTL) associated with drought tolerance in maize were identified, of which 20 were determined as core MQTL. The average confidence interval of MQTL was strongly reduced compared to that of the previously published QTL. Nearly half of the MQTL were confirmed by co-localized marker-trait associations from genome-wide association studies. Based on the alignment of rice proteins related to drought tolerance, 63 orthologous genes were identified near the maize MQTL. Furthermore, 583 candidate genes were identified within the 20 core MQTL regions and maize-rice homologous genes. Based on KEGG analysis of candidate genes, plant hormone signaling pathways were found to be significantly enriched. The signaling pathways can have direct or indirect effects on drought tolerance and also interact with other pathways. In conclusion, this study provides novel insights into the genetic and molecular mechanisms of drought tolerance in maize towards a more targeted improvement of this important trait in breeding.

Single-Shot Readout of a Solid-State Electron Spin Qutrit.

Quantum systems usually feature a rich multilevel structure with promising resources for developing superior quantum technologies compared with their binary counterpart. Single-shot readout of these high-dimensional quantum systems is essential for exploiting their potential. Although there have been various high-spin systems, the single-shot readout of the overall state of high-spin systems remains a challenging issue. Here we demonstrate a reliable single-shot readout of spin qutrit state in a low-temperature solid-state system utilizing a binary readout scheme. We achieve a single-shot readout of an electron spin qutrit associated with a single nitrogen-vacancy center in diamond with an average fidelity of 87.80%. We use this spin qutrit system to verify quantum contextuality, a fundamental test of quantum mechanics. We observe a violation of the noncontextual hidden variable inequality with the developed single-shot readout in contrast to the conventional binary readout. These results pave the way for developing quantum information processing based on spin qutrits.

Armored Superhydrophobic Surfaces with Excellent Drag Reduction in Complex Environmental Conditions.

Superhydrophobic surfaces (SHSs) have possibilities for achieving significantly reduced solid-liquid frictional drag in the marine sector due to their excellent water-repelling properties. Although the stability of SHSs plays a key role in drag reduction, little consideration was given to the effect of extreme environments on the ability of SHSs to achieve drag reduction underwater, particularly when subjected to acidic conditions. Here, we propose interconnected microstructures to protect superhydrophobic coatings with the aim of enhancing the stability of SHSs in extreme environments. The stability of armored SHSs (ASHSs) was demonstrated by the contact angle and bounce time of droplets on superhydrophobic surfaces treated by various methods, resulting in an ASHS surface with excellent stability under extreme environmental conditions. Additionally, inspired by microstructures protecting superhydrophobic nanomaterials from frictional wear, the armored superhydrophobic spheres (ASSPs) were designed to explain from theoretical and experimental perspectives why ASSPs can achieve sustainable drag reduction and demonstrate that the ASSPs can achieve drag reduction of over 90.4% at a Reynolds number of 6.25 × 104 by conducting water entry experiments on spheres treated in various solutions. These studies promote a fundamental understanding of what drives the application of SHSs under extreme environmental conditions and provide practical strategies to maximize frictional drag reduction.

Endosome associated trafficking regulator 1 promotes tumor growth and invasion of glioblastoma multiforme via inhibiting TNF signaling pathway.

PURPOSE: Endosome associated trafficking regulator 1 (ENTR1) is a novel endosomal protein, which can affect multiple cellular biological behavior by remodeling plasma membrane structures. However, little is known regarding its function and underlying mechanisms in glioblastoma multiforme. METHODS: Expression profile and clinical signature were obtained from The Public Database of human tumor. Immunohistochemical staining and western blotting assays were used to measure ENTR1 expression level. Human primary GBM tumor cells and human GBM cell lines A172, U87 and U251 were used to clarify the precise role of ENTR1. CCK-8 assays, wound healing and transwell invasion assays were designed to investigate cell viability, invasion and migration of GBM cells, respectively. Underlying molecular mechanisms of ENTR1 were determined via RNA-seq analysis. Tumor formation assay was used to validate the influence of ENTR1 in vivo. RESULTS: Compared with normal brain tissues, ENTR1 was highly expressed in gliomas and correlated with malignant grades of gliomas and poor overall survival time. The proliferation and invasion of GBM cells could be weaken and the sensitivity to temozolomide (TMZ) chemotherapy increased after knocking down ENTR1. Overexpression of ENTR1 could reverse this effect. RNA-seq analysis showed that tumor necrosis factor (TNF) signaling pathway might be a putative regulatory target of ENTR1. Tumor formation assay validated that ENTR1 was a significant factor in tumor growth. CONCLUSION: Our results indicated that ENTR1 played an important role in cell proliferation, invasion and chemotherapeutic sensitivity of GBM, suggesting that ENTR1 might be a novel prognostic marker and significant therapeutic target for GBM.

Suppressed Droplet Splashing on Positively Skewed Surfaces for High-Efficiency Evaporation Cooling.

Two types of functional surfaces with the same roughness but completely different surface topographies are prepared, namely positively skewed surfaces filled with micropillar arrays (Sa ≈4.4 µm, Ssk >0) and negatively skewed surfaces filled with microcavity arrays (Sa ≈4.4 µm, Ssk <0), demonstrating promoting droplet splashing. Remarkably, the critical Weber number for generating satellite droplets on the negatively skewed surfaces is significantly lower than that on the positively skewed surfaces, indicating that the negatively skewed surface with microcavity arrays is more likely to promote droplet splashing. It is mainly attributed to the fact that air on the negatively skewed surface can make the liquid film take on a Cassie-Baxter state on the surface so that the stabilizing capillary force of the liquid film exceeds the destabilizing stress of the air film. Moreover, the surface topography promoting droplet spreading and the mechanical properties of three-phase moving contact lines are analyzed from the perspective of microscopic interface mechanics. Finally, it is demonstrated the designed positively skewed surfaces can be employed for large-area heat dissipation by means of high-efficiency evaporation.

Paeoniflorin inhibits colorectal cancer cell stemness through the miR-3194-5p/catenin beta-interacting protein 1 axis.

Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/ß-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/ß-catenin axis to repress CRC cell stemness.

Dynamic Behavior of Droplet Impact on Laminar Superheated Particles.

The impact of droplets on particles involves a wide range of complex phenomena and mechanisms, including bubble nucleation, crater formation, fluidization, and more intricate changes in the boiling regime when impacting superheated particles. In this study, we focus on droplet impact behavior on superheated laminar particles at various temperatures and define six typical characteristic patterns of a single droplet impact on superheated laminar particles, including film evaporation, bubbly boiling, immersion boiling, sputter boiling, transition boiling, and film boiling. It is worth noting that the variations of inertial force FI caused by gravity, the capillary force FC generated by the pores of the droplets, and the dewetting force by the vapor phase FV are the main contributors to different evaporation regimes. Interestingly, we find that the Leidenfrost point (LFP) of droplets on the laminar superheated particles decreases with particle size, which is related to the effect of the pore space generated between the laminar particles. Finally, the effect of temperature, particle size, and Weber number (We) on the dynamic behavior of droplet impact is revealed. Experimental results show that the instantaneous diameter of droplets is inversely proportional to the change of height, with different patterns of maximum spreading diameter and maximum bounce height at different particle sizes, while the maximum spreading velocity and maximum bounce velocity are independent of particle size. We believe the present work would provide a broader knowledge and comprehension of the droplet impact on heated particles and promote the development of the safety and productivity of industrial processes such as fluid catalytic cracking, spray drying, and spray cooling.

Delayed Leidenfrost Effect of a Cutting Droplet on a Microgrooved Tool Surface.

Regulation over the generation of the Leidenfrost phenomenon in liquids is vitally important in a cutting fluid/tool system, with benefits ranging from optimizing the heat transfer efficiency to improving the machining performance. However, realizing the influence mechanism of liquid boiling at various temperatures still faces enormous challenges. Herein, we report a kind of microgrooved tool surface by laser ablation, which could obviously increase both the static and dynamic Leidenfrost point of cutting fluid by adjusting the surface roughness (Sa). The physical mechanism that delays the Leidenfrost effect is primarily due to the ability of the designed microgroove surface to store and release vapor during droplet boiling so that the heated surface requires higher temperatures to generate sufficient vapor to suspend the droplet. We also find six typical impact regimes of cutting fluid under various contact temperatures; it is worth noting that Sa has a great influence on the transform threshold among six impact regimes, and the likelihood that a droplet will enter the Leidenfrost regime decreases with increasing Sa. In addition, the synergistic effect of Sa and tool temperature on the droplet kinetics of cutting droplets is investigated, and the relationship between the maximum rebound height and the dynamic Leidenfrost point is correlated for the first time. Significantly, cooling experiments on the heated microgrooved surface are performed and demonstrate that it is effective to improve the heat dissipation ability of cutting fluid by delaying the Leidenfrost effect on the microgrooved heated surface.

Expression and functional activity of myosin II in hyperplastic prostates of varying volumes.

Prostate volume (PV) differs dramatically among benign prostatic hyperplasia (BPH) patients. Estimation of PV is important to guide the most appropriate pharmacologic or interventional treatment approach. However, the underlying pathophysiological mechanisms for the differences in PV remain unknown. We recently found that the myosin II system might participate in the etiology and development of BPH via static and dynamic factors. Our present study aims to explore the expression and functional activities of myosin II isoforms including smooth muscle (SM) myosin II (SMM II) and non-muscle myosin II (NMM II) in hyperplastic prostates with varied PV. Human hyperplastic prostates and the testosterone-induced rat BPH model were employed for this study. Hematoxylin and Eosin (H&E), Masson's trichrome, immunohistochemical staining, in vitro organ bath, RT-polymerase chain reaction (PCR) and Western-blotting were performed. Also, a BPH tissue microarray (TMA) was constructed to determine the correlations between myosin II isoforms with clinical parameters of BPH patients. With the increase of PV, the expression of NMMHC-A, NMMHC-C, SM-A and LC17b isoforms were increased, and the contractility of prostate smooth muscle was enhanced but force developed more slowly. Consistently, NMMHC-A, NMMHC-C, SM-A and LC17b were correlated positively with PV. Similar outcomes were also observed in the BPH rat model with different PVs. Alterations in the expression and function of myosin the II system may be involved in the pathophysiological mechanism of PV differences between BPH patients.

LILRB2-containing small extracellular vesicles from glioblastoma promote tumor progression by promoting the formation and expansion of myeloid-derived suppressor cells.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) was reported to be an inhibitory molecule with suppressive functions. sEVs mediate communication between cancer cells and other cells. However, the existence of LILRB2 on sEVs in circulation and the function of sEVs-LILRB2 are still unknown. This study aims to investigate the role of LILRB2 in GBM and determine how LILRB2 in sEVs regulates tumor immunity. METHODS: LILRB2 expression in normal brain and GBM tissues was detected by immunohistochemistry, and the effect of LILRB2 on prognosis was evaluated in an orthotopic brain tumor model. Next, a subcutaneous tumor model was constructed to evaluate the function of pirb in vivo. The immune cells in the tumor sites and spleen were detected by immunofluorescence staining and flow cytometry. Then, the presence of pirb in sEVs was confirmed by WB. The percentage of immune cells after incubation with sEVs from GL261 (GL261-sEVs) or sEVs from GL261-pirb+ (GL261-sEVs-pirb) was detected by flow cytometry. Then, the effect of pirb on sEVs was evaluated by a tumor-killing assay and proliferation assay. Finally, subcutaneous tumor models were constructed to evaluate the function of pirb on sEVs. RESULTS: LILRB2 was overexpressed in human GBM tissue and was closely related to an immunosuppressive TME in GBM. Then, a protumor ability of LILRB2 was observed in subcutaneous tumor models, which was related to lower CD8 + T cells and higher MDSCs (myeloid-derived suppressor cells) in the tumor and spleen compared to those of the control group. Next, we found that pirb on sEVs (sEVs-pirb) inhibits the function of CD8 + T cells by promoting the formation and expansion of MDSCs. Furthermore, the protumor function of sEVs-pirb was demonstrated in subcutaneous tumor models. CONCLUSION: We discovered that LILRB2/pirb can be transmitted between GBM cells via sEVs and that pirb on sEVs induces the formation and expansion of MDSCs. The induced MDSCs facilitate the formation of an immunosuppressive TME.

DHCR7 promotes tumorigenesis via activating PI3K/AKT/mTOR signalling pathway in bladder cancer.

Bladder cancer (BCa) is a common malignancy with uncertain molecular mechanism. 7-dehydrocholesterol reductase (DHCR7), the enzyme of mammalian sterol biosynthesis, plays important roles in several types of cancers but its specific function in BCa is still unknown. The current study aimed to determine the bioinformatic characteristics and biological functions of DHCR7 in BCa. Sequencing results and clinical data from online public databases, human BCa tissues and matched noncancerous tissues, xenograft nude mice, DHCR7 deficiency and overexpression BCa cell (T24 and EJ) models were used. Several bioinformatics analyses were made, qRT-PCR, Western-blotting, flow cytometry, immunohistochemistry (IHC), MTT assay, wound healing and cell invasion assays were performed. It was found that DHCR7 was upregulated in BCa as an independent risk factor, and the expression of DHCR7 was associated with BCa grade and stage, finally resulted in poor prognosis. We further demonstrated that DHCR7 overexpression could accelerate the G0/G1 phase to accelerate the growth of tumor cells, antagonize cell apoptosis, and enhance the invasion and migration capacity, as well as EMT process via PI3K/AKT/mTOR signalling pathway, which could be completely reversed by DHCR7 knockdown. Finally, DHCR7 deficiency significantly decreased tumorigenesis in vivo. Our novel data demonstrated that DHCR7 could modulate BCa tumorigenesis in vitro and in vivo via PI3K/AKT/mTOR signalling pathway. It is suggested that DHCR7 might become a molecular target for the diagnosis and treatment of BCa.

Genetic Dissection of Phosphorus Use Efficiency and Genotype-by-Environment Interaction in Maize.

Genotype-by-environment interaction (G-by-E) is a common but potentially problematic phenomenon in plant breeding. In this study, we investigated the genotypic performance and two measures of plasticity on a phenotypic and genetic level by assessing 234 maize doubled haploid lines from six populations for 15 traits in seven macro-environments with a focus on varying soil phosphorus levels. It was found intergenic regions contributed the most to the variation of phenotypic linear plasticity. For 15 traits, 124 and 31 quantitative trait loci (QTL) were identified for genotypic performance and phenotypic plasticity, respectively. Further, some genes associated with phosphorus use efficiency, such as Zm00001eb117170, Zm00001eb258520, and Zm00001eb265410, encode small ubiquitin-like modifier E3 ligase were identified. By significantly testing the main effect and G-by-E effect, 38 main QTL and 17 interaction QTL were identified, respectively, in which MQTL38 contained the gene Zm00001eb374120, and its effect was related to phosphorus concentration in the soil, the lower the concentration, the greater the effect. Differences in the size and sign of the QTL effect in multiple environments could account for G-by-E. At last, the superiority of G-by-E in genomic selection was observed. In summary, our findings will provide theoretical guidance for breeding P-efficient and broadly adaptable varieties.

Using machine learning models to predict the duration of the recovery of COVID-19 patients hospitalized in Fangcang shelter hospital during the Omicron BA. 2.2 pandemic.

Background: Factors that may influence the recovery of patients with confirmed SARS-CoV-2 infection hospitalized in the Fangcang shelter were explored, and machine learning models were constructed to predict the duration of recovery during the Omicron BA. 2.2 pandemic. Methods: A retrospective study was conducted at Hongqiao National Exhibition and Convention Center Fangcang shelter (Shanghai, China) from April 9, 2022 to April 25, 2022. The demographics, clinical data, inoculation history, and recovery information of the 13,162 enrolled participants were collected. A multivariable logistic regression model was used to identify independent factors associated with 7-day recovery and 14-day recovery. Machine learning algorithms (DT, SVM, RF, DT/AdaBoost, AdaBoost, SMOTEENN/DT, SMOTEENN/SVM, SMOTEENN/RF, SMOTEENN+DT/AdaBoost, and SMOTEENN/AdaBoost) were used to build models for predicting 7-day and 14-day recovery. Results: Of the 13,162 patients in the study, the median duration of recovery was 8 days (interquartile range IQR, 6-10 d), 41.31% recovered within 7 days, and 94.83% recovered within 14 days. Univariate analysis showed that the administrative region, age, cough medicine, comorbidities, diabetes, coronary artery disease (CAD), hypertension, number of comorbidities, CT value of the ORF gene, CT value of the N gene, ratio of ORF/IC, and ratio of N/IC were associated with a duration of recovery within 7 days. Age, gender, vaccination dose, cough medicine, comorbidities, diabetes, CAD, hypertension, number of comorbidities, CT value of the ORF gene, CT value of the N gene, ratio of ORF/IC, and ratio of N/IC were related to a duration of recovery within 14 days. In the multivariable analysis, the receipt of two doses of the vaccination vs. unvaccinated (OR = 1.118, 95% CI = 1.003-1.248; p = 0.045), receipt of three doses of the vaccination vs. unvaccinated (OR = 1.114, 95% CI = 1.004-1.236; p = 0.043), diabetes (OR = 0.383, 95% CI = 0.194-0.749; p = 0.005), CAD (OR = 0.107, 95% CI = 0.016-0.421; p = 0.005), hypertension (OR = 0.371, 95% CI = 0.202-0.674; p = 0.001), and ratio of N/IC (OR = 3.686, 95% CI = 2.939-4.629; p < 0.001) were significantly and independently associated with a duration of recovery within 7 days. Gender (OR = 0.736, 95% CI = 0.63-0.861; p < 0.001), age (30-70) (OR = 0.738, 95% CI = 0.594-0.911; p < 0.001), age (>70) (OR = 0.38, 95% CI = 0292-0.494; p < 0.001), receipt of three doses of the vaccination vs. unvaccinated (OR = 1.391, 95% CI = 1.12-1.719; p = 0.0033), cough medicine (OR = 1.509, 95% CI = 1.075-2.19; p = 0.023), and symptoms (OR = 1.619, 95% CI = 1.306-2.028; p < 0.001) were significantly and independently associated with a duration of recovery within 14 days. The SMOTEEN/RF algorithm performed best, with an accuracy of 90.32%, sensitivity of 92.22%, specificity of 88.31%, F1 score of 90.71%, and AUC of 89.75% for the 7-day recovery prediction; and an accuracy of 93.81%, sensitivity of 93.40%, specificity of 93.81%, F1 score of 93.42%, and AUC of 93.53% for the 14-day recovery prediction. Conclusion: Age and vaccination dose were factors robustly associated with accelerated recovery both on day 7 and day 14 from the onset of disease during the Omicron BA. 2.2 wave. The results suggest that the SMOTEEN/RF-based model could be used to predict the probability of 7-day and 14-day recovery from the Omicron variant of SARS-CoV-2 infection for COVID-19 prevention and control policy in other regions or countries. This may also help to generate external validation for the model.

Functional Microtextured Superhydrophobic Surface with Excellent Anti-Wear Resistance and Friction Reduction Properties.

The wear-resistant superhydrophobic (SHB) surfaces with excellent water-repellency ability were prepared by constructing a microtextured armor on an aluminum surface. With the assistance of laser-induced microtextures, the SHB surface could keep a longer water-repellency ability and a lower friction coefficient even after repeated friction tests under different loads and at different speeds. The mechanism of microtexture-protecting SHB coating is revealed based on both theoretical and elemental analysis. Additionally, we explore the relationship between the three-dimensional topography parameters (ISO 25178) and variation of water contact angles under different test recycles. The results show that the rough surface with appropriate Sa and higher Sku exhibits a better wear resistance, which is mainly related to the storing ability of SHB coating inside the microtextures. Moreover, the surface with appropriate Str exhibits excellent wear resistance, which is mainly associated with better chip-removal ability. Finally, the tribological properties of the microtextured SHB surface are researched. It is worth noting that compared with the microtextured surface without SHB coating and the SHB-coated surface without microtextures, the microtextured SHB surface has the lowest friction coefficient under dry friction because the SHB coating would largely decrease the surface energy of the interface, so the adhesion friction decreases. The microtexture armor on the surfaces would protect the wear of SHB coating, so the SHB coating inside the microtexture could continuously play the role of a particle lubricant at the sliding interface and decrease the friction force of the sliding interface. We believe that the present study would contribute to the further understanding of the constructing mechanism of anti-wear SHB surfaces and provide a new strategy for topography design of engineering surfaces with friction reduction properties.

Structural design and analysis of pneumatic prostate seed implantation robot applied in magnetic resonance imaging environment.

BACKGROUND: The method of MRI (Magnetic Resonance Imaging) image-guided robot for prostate seed implantation has developed rapidly in recent years. During the operation, although the puncture effect guided by MRI is very good, it is difficult for conventional robots driven by motors to work normally in this environment, which reduces the accuracy of seed implantation and affects the treatment effect. METHODS: First, this paper designs a pneumatic prostate seed implantation robot that is compatible with MRI; the robot is composed of an execution module and an adjustment module, and can complete the positioning and adjustment of the robot's needle entry point, the pose adjustment of the puncture needle and the completion of seed implantation in the MRI space; meanwhile, the statics simulation analysis of its key components is carried out. Then, the kinematics analysis was carried out according to the designed robot structure, and the relationship between the posture of the needle tip and the change of the pneumatic cylinder was obtained; meanwhile, using MATLAB 2020 software, combined with the method of Monte Carlo random number sampling, the simulation analysis of the workspace was carried out. Finally, an experimental prototype is constructed to conduct puncture accuracy experiments, workspace experiments and performance comparison tests in MRI environment. RESULTS: The statics simulation results verify that the key components of the robot designed in this paper can meet the strength requirements of the robot. The simulation results of the workspace meet the requirements of space surgery for prostate seed implantation under the guidance of MRI environment. The puncture accuracy experimented to verify that increasing the puncture speed can improve the seed implantation accuracy, and the puncture deviation of the robot is less than the average deviation of the doctor's actual operation by 6.5 mm. The working space experiment shows that the pitch range is -23.3°~27.8°, the movement range in the X direction is 0~210 mm, the movement range in the Y direction is 0~101 mm, and the lifting range in the Z direction is 0~81 mm, which meets the workspace requirements under MRI. The performance comparison test results in the MRI environment show that the robot is well compatible with MRI instruments. CONCLUSIONS: The pneumatic prostate seed implantation robot designed in this paper has a reasonable structure and stable dynamic performance output, and can perform precise surgical operations in the MRI strong magnetic environment. The research work in this paper provides a design reference for the related research on the positioning accuracy of minimally invasive puncture surgery guided by MRI images.

Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS-STAT3 pathway.

OBJECTIVE: To investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transducer and activator of transcription 3 (STAT3) signalling in gastric cancer cell lines. METHODS: In vivo tumour xenograft anticancer assays were undertaken to confirm the anticancer activity of PL. Cell viability, flow cytometry and Western blot assays were undertaken to evaluate the anticancer effects of PL, VC and combinations of PL and VC in AGS and KATO III cells. RESULTS: Both PL and VC induced apoptosis and inhibited cell proliferation in AGS and KATO III cells. These effects were dependent on reactive oxygen species (ROS). PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3. The combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone. PL reversed the abnormal activation of STAT3 by VC, which could be a key to their synergistic effect. CONCLUSIONS: PL combined with VC exhibited a stronger anticancer effect by regulating the ROS-STAT3 pathway, suggesting that this combination might be a potential adjuvant therapy for gastric cancer.

Eliminating the original cargos of glioblastoma cell-derived small extracellular vesicles for efficient drug delivery to glioblastoma with improved biosafety.

Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded proteins or RNAs) from parent cancer cells in tumor progression severely hinder the practical application. In this study, a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore, doxorubicin (DOX) transported by the saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.