CD63, a member of transmembrane-4-superfamily of tetraspanin proteins and a highly N-glycosylated type III lysosomal membrane protein, is known to regulate malignancy of various types of cancers such ...as melanoma and breast cancer and serves as a potential marker for cancer detection. Recently, its important role as a classic exosome marker was also emphasized. In this work, via using a magnetic bead-based competitive SELEX (systematic evolution of ligands by exponential enrichment) procedure and introducing a 0.5M NaCl as elution buffer, we identified two DNA aptamers (CD63-1 and CD63-2) with high affinity and specificity to CD63 protein (
= 38.71nM and 78.43, respectively). Furthermore, CD63-1 was found to be efficient in binding CD63 positive cells, including breast cancer MDA-MB-231 cells and CD63-overexpressed HEK293T cells, with a medium binding affinity (
~ 100 nM) as assessed by flow cytometry. When immunostaining assay was performed using clinical breast cancer biopsy, the CD63-1 aptamer demonstrated a comparable diagnostic efficacy for CD63 positive breast cancer with commercial antibodies. After developing a magnetic bead-based exosome immunoaffinity separation system using CD63-1 aptamer, it was found that this bead-based system could effectively isolate exosomes from both MDA-MB-231 and HT29 cell culture medium. Importantly, the introduction of the NaCl elution in this work enabled the isolation of native exosomes via a simple 0.5M NaCl incubation step. Based on these results, we firmly believe that the developed aptamers could be useful towards efficient isolation of native state exosomes from clinical samples and various theranostic applications for CD63-positive cancers.
With the progression of marine exploration and exploitation, as well as the advancements in mechanical intelligence, the utilization of the unmanned surface vehicle (USV) and the design of their ...guidance system have become prominent areas of focus. However, the stern ramp recovery of the USV is still in its infancy due to its unique attitude requirements and automation design. Furthermore, few studies have addressed the impact of maritime disturbances, with most research limited to simulations. To enhance the efficiency and accuracy of stern ramp recovery, this paper presents the development and construction of a novel recovery system. By incorporating physical modeling of disturbance forces acting on USVs at sea, the practicality of the system is improved. Additionally, an optimized genetic algorithm is introduced in the navigation module to improve convergence rates and subsequently enhance recovery efficiency. A line-of-sight (LOS) algorithm based on average velocity is proposed in this paper to ensure the attainment of unique attitude requirements and to improve the effectiveness of stern chute recovery. This paper provides a detailed description of the independently designed USV hardware system. Moreover, simulations and practical experiments conducted using this experimental platform are presented, offering a new solution for the USV’s stern ramp recovery.
Genes or their encoded products are not expected to mingle with each other unless in some disease situations. In cancer, a frequent mechanism that can produce gene fusions is chromosomal ...rearrangement. However, recent discoveries of RNA trans-splicing and cis-splicing between adjacent genes (cis-SAGe) support for other mechanisms in generating fusion RNAs. In our transcriptome analyses of 28 prostate normal and cancer samples, 30% fusion RNAs on average are the transcripts that contain exons belonging to same-strand neighboring genes. These fusion RNAs may be the products of cis-SAGe, which was previously thought to be rare. To validate this finding and to better understand the phenomenon, we used LNCaP, a prostate cell line as a model, and identified 16 additional cis-SAGe events by silencing transcription factor CTCF and paired-end RNA sequencing. About half of the fusions are expressed at a significant level compared to their parental genes. Silencing one of the in-frame fusions resulted in reduced cell motility. Most out-of-frame fusions are likely to function as non-coding RNAs. The majority of the 16 fusions are also detected in other prostate cell lines, as well as in the 14 clinical prostate normal and cancer pairs. By studying the features associated with these fusions, we developed a set of rules: 1) the parental genes are same-strand-neighboring genes; 2) the distance between the genes is within 30kb; 3) the 5' genes are actively transcribing; and 4) the chimeras tend to have the second-to-last exon in the 5' genes joined to the second exon in the 3' genes. We then randomly selected 20 neighboring genes in the genome, and detected four fusion events using these rules in prostate cancer and non-cancerous cells. These results suggest that splicing between neighboring gene transcripts is a rather frequent phenomenon, and it is not a feature unique to cancer cells.
Geopolymers show great potential in complex wastewater treatment to improve water quality. In this work, general geopolymers, porous geopolymers and geopolymer microspheres were prepared by the ...suspension curing method using three solid waste products, coal gangue, fly ash and blast furnace slag. The microstructure, morphology and surface functional groups of the geopolymers were studied by SEM, XRD, XRF, MIP, FTIR and XPS. It was found that the geopolymers possess good adsorption capacities for both organic and inorganic pollutants. With methylene blue and potassium dichromate as the representative pollutants, in order to obtain the best removal rate, the effects of the adsorbent type, dosage of adsorbent, concentration of methylene blue and potassium dichromate and pH on the adsorption process were studied in detail. The results showed that the adsorption efficiency of the geopolymers for methylene blue and potassium dichromate was in the order of general geopolymers < porous geopolymers < geopolymer microspheres, and the removal rates were up to 94.56% and 79.46%, respectively. Additionally, the competitive adsorption of methylene blue and potassium dichromate in a binary system was also studied. The mechanism study showed that the adsorption of methylene blue was mainly through pore diffusion, hydrogen bond formation and electrostatic adsorption, and the adsorption of potassium dichromate was mainly through pore diffusion and redox reaction. These findings demonstrate the potential of geopolymer microspheres in adsorbing organic and inorganic pollutants, and, through five cycles of experiments, it is demonstrated that MGP exhibits excellent recyclability.
Due to booming economic development over the past decades, energy demands in most of China’s provincial power grids have increased sharply, and it has become challenging to guarantee the energy ...balance at peak periods. In many provincial electric systems of China, gas-fired generators are one of the most important peaking power sources to respond the load change at peak periods. To meet this practical necessity, a novel mixed integer linear programming model is proposed in this paper for the peak operation of gas-fired generating units with disjoint-prohibited operating zones. In the developed model, the objective function is chosen to minimize the peak-valley difference of the remaining load series that is obtained by subtracting the total generation of all the gas-fired units from the original load curve. The real-world simulations in several cases show that the developed model is able to generate satisfying scheduling results by reasonably allocating the power outputs of all the gas-fired generators in the scheduling horizon. Then, the management implications obtained lie in the fact that it is necessary to increase the share of peak power sources in the mid- to long-term planning of an electrical power system; and in the daily operation of the power grid, greater flexibility should be given to the gas-fired units to reduce peak pressure.
The supercritical carbon dioxide (S–CO2) Brayton cycle is an important energy conversion technology for the fourth generation of nuclear energy. Since the printed circuit heat exchanger (PCHE) used ...in the S–CO2 Brayton cycle has narrow channels, Rayleigh-Bénard (RB) convection is likely to exist in the tiny channels. However, there are very few studies on RB convection in supercritical fluids. Current research on RB convection mainly focuses on conventional fluids such as water and air that meet the Boussinesq assumption. It is necessary to study non-Boussinesq fluids. PRB convection refers to RB convection that is affected by horizontal incoming flow. In this paper, the computational fluid dynamics simulation method is used to study the PRB convection phenomenon of non-Boussinesq fluid-supercritical carbon dioxide. The result shows that the inlet Reynolds number (Re) of the horizontal incoming flow significantly affects the PRB convection. When the inlet Re remains unchanged, with the increase of Rayleigh number (Ra), the steady-state convective pattern of the fluid layer is shown in order: horizontal flow, local traveling wave, traveling wave convection. If Ra remains unchanged, as the inlet Re increases, three convection patterns of traveling wave convection, local traveling wave, and horizontal flow will appear in sequence. To characterize the relationship between traveling wave convection and horizontal incoming flow, this paper proposes the relationship between critical Reynolds number and relative Rayleigh number (r).
The Euler-Euler model is less effective in capturing the free surface of flow film in the spiral separator, and thus a Eulerian multi-fluid volume of fluid (VOF) model was first proposed to describe ...the particulate flow in spiral separators. In order to improve the applicability of the model in the high solid concentration system, the Bagnold effect was incorporated into the modelling framework. The capability of the proposed model in terms of predicting the flow film shape in a LD9 spiral separator was evaluated via comparison with measured flow film thicknesses reported in literature. Results showed that sharp air–water and air-pulp interfaces can be obtained using the proposed model, and the shapes of the predicted flow films before and after particle addition were reasonably consistent with the observations reported in literature. Furthermore, the experimental and numerical simulation of the separation of quartz and hematite were performed in a laboratory-scale spiral separator. When the Bagnold lift force model was considered, predictions of the grade of iron and solid concentration by mass for different trough lengths were more consistent with experimental data. In the initial development stage, the quartz particles at the bottom of the flow layer were more possible to be lifted due to the Bagnold force. Thus, a better predicted vertical stratification between quartz and hematite particles was obtained, which provided favorable conditions for subsequent radial segregation.
Due to the existence of an inlet elbow, transmission shaft, and other structural components, the inflow of axial-flow pumps as turbines (PATs) becomes non-uniform, resulting in the complexity of ...internal flow and adverse effects such as structural vibration. In this paper, numerical methods were employed to explore the non-uniform inflow effects on impeller forces and internal flow field characteristics within an axial-flow PAT. The study results indicated that non-uniform inflow caused uneven pressure distribution inside the impeller, which leads to an imbalance in radial forces and offsetting the center of radial forces. With an increasing flow rate, the asymmetry of radial forces as well as the amplitude of their fluctuations increased. Non-uniform inflow was found to induce unstable flow structures inside the impeller, leading to low-frequency, high-amplitude pressure fluctuations near the hub. Using the enstrophy transport equation, it was shown that the relative vortex generation term played a major part in the spatiotemporal evolution of vortices, with minimal viscous effects.
Abstract
Background
Pancreatoduodenectomy (PD) is traumatic, difficult to perform, and has a high incidence of postoperative complications and perioperative mortality. Postoperative complications and ...pain occur frequently and seriously affect the psychological status of patients. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has analgesic and antidepressant effects. In this study, we aim to investigate the effect of esketamine on postoperative depression and pain in patients undergoing PD.
Methods/design
This prospective, single-center, randomized control trial will include 80 patients who will undergo elective PD. The patients will be randomly assigned to two groups: the experimental group that will receive esketamine (
n
= 40) and the control group (
n
= 40). In the esketamine group, the analgesic pump will be connected immediately after surgery. A solution of esketamine 1.5 mg/kg + sufentanil 2 µg/kg, diluted to 150 mL, will be administered continuously for 72 h at the background infusion and impact doses of 1 mL/h and 2 mL/time, respectively; the locking time will be 10 min. The control group will receive sufentanil 2 µg/kg that will be administered as per the esketamine group. The primary outcome will be the Hamilton Depression Scale (HAMD-17) score on the third day post-surgery (POD3). Secondary study indicators will include (1) visual analog scale (VAS) score and HAMD-17 score prior to surgery, immediately after entering the postanesthesia care unit (PACU) and 1, 2, 3, 4, and 5 days after surgery; (2) Richmond Agitation-Sedation Scale (RASS) score at 1, 2, 3, 4, and 5 days after surgery; (3) consumed doses of sufentanil and esketamine after surgery; (4) postoperative analgesia pump effective press times, rescue analgesia times, and rescue drug dosage, recording the number of rescue analgesia and rescue drug dosage at 6, 24, 48, and 72 h after the patient enters the PACU; (5) postoperative complications and adverse events; (6) postoperative hospital stay; (7) concentrations of brain-derived neurotrophic factor (BDNP), 5-hydroxytryptamine (5-HT), tumor necrosis factor (TNF-α) and interleukin-6, at 1, 3, and, 5 days post-surgery; and (8) the patient survival rate at 6 and 12 months post-surgery.
Discussion
The study hypothesis is that the postoperative HAMD-17 and VAS scores, incidence of postoperative adverse reactions, and concentration of serum markers BDNP, 5-HT, TNF-α, and IL-6 in the experimental group will be lower than those in the control group.
Trial registration
ClinicalTrials.gov ChiCTR2200066303. Registered on November 30, 2022.
Protocol version: 1.0
Background
Esophageal squamous cell carcinoma is the predominant subtype of esophageal cancer in China and so differs from presentations in Western countries. Common metastatic locations of ...esophageal cancer include the liver, lung, bone, and brain. In contrast, metastases in subcutaneous soft tissue are exceedingly rare.
Case presentation
We present the experience of a 57-year-old man with a complaint of hand and leg dysfunction on the right side. He had a past medical history of esophageal squamous cell carcinoma. Further imaging workup revealed a solitary brain metastasis, thickening of the esophageal wall, swollen lymph nodes in the mediastinum, and right adrenal gland metastasis. Gamma knife radiosurgery of the brain metastasis and intensity-modulated radiotherapy of the esophagus and lymph nodes were administered. After 1.5 months, he was admitted to our hospital again, and nodules were identified in the anterior abdominal wall and left posterior chest wall. Ultrasound, CT, and radical excision of the abdominal wall mass were undertaken and revealed metastatic squamous cell carcinoma with neuroendocrine differentiation. We administered immunotherapy followed by targeted therapy. A PET/CT scan was performed to identify other organ metastases; the scan revealed multiple areas of fluorodeoxyglucose uptake and foci in the esophagus, lung, liver, bone, and right adrenal gland; and in various lymph nodes. In addition, an intensely hypermetabolic lesion was localized in the left posterior thorax.
Conclusion
This case highlights the diagnosis and treatment of uncommon metastases of esophageal squamous cell carcinoma. We hope that our clinical experience provides insights into these uncommon metastases.
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