TMCO1 regulates cell proliferation, metastasis and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance.

This study aimed to explore the involvement of Transmembrane and coiled-coil domains 1 (TMCO1) in ovarian cancer progression and its regulatory mechanisms in cisplatin resistance. Using the GEPIA database, we analyzed TMCO1 expression in ovarian cancer and normal tissues. In a cohort of 99 ovarian cancer patients, immunohistochemistry and immunofluorescence were employed to assess TMCO1 expression in tumor and adjacent tissues, correlating findings with clinical and pathological characteristics. TMCO1 overexpression and knockout cell models were constructed, and their impact on non-cisplatin-resistant (SK-OV-3) and cisplatin-resistant (SK-OV-3-CDDP) ovarian cancer cells was investigated through cloning, wound healing, Fluo 4, and Transwell experiments. Knocking down CALR and VDAC1 was performed to examine their effects on TMCO1, cell proliferation, and malignant markers. Subcutaneous tumor models in nude mice elucidated the in vivo role of TMCO1 in tumor growth. Expression levels of CALR, VDAC1, angiogenesis indicators (CD34), and epithelial-mesenchymal transition (EMT) markers were evaluated. TMCO1 expression in ovarian cancer tissue significantly differed from normal tissue, correlating with survival rates. TMCO1 overexpression was associated with lymph node metastases, late FIGO stage, and larger tumors. TMCO1 promoted proliferation, calcium ion elevation, cytoskeletal remodeling, and metastasis in SK-OV-3 and SK-OV-3-CDDP cells, upregulating VDAC1, CALR, Vimentin, N-cadherin, ß-catenin, and downregulating E-cadherin. Silencing TMCO1 inhibited cell growth, proliferation, and angiogenesis in vivo, suppressing the expression of CALR, VDAC1, Vimentin, N-cadherin, and ß-catenin. Overall, this study highlighted TMCO1 as a crucial regulator in ovarian cancer progression, influencing VDAC1 through CALR and impacting diverse cellular processes, offering potential as a targeted therapeutic strategy for ovarian cancer.

Efficacy and safety of intraoperative controlled hypotension: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Intraoperative controlled hypotension improves surgical field visibility by reducing blood loss (efficacy) but poses potential risks linked to organ hypoperfusion (safety). The use of controlled hypotension persists despite increasing evidence of associations between intraoperative inadvertent hypotension and adverse outcomes. Therefore, we tested the hypothesis that the focus and results of intraoperative controlled hypertension research differ across anaesthesia and surgery investigators because of differing priorities. METHODS: We systematically reviewed randomised trials comparing controlled hypotension with usual care with trials categorised by investigators' affiliation. RESULTS: We identified 48 eligible trials, of which 37 were conducted by anaesthesia investigators and 11 by surgery investigators. For the primary outcome, 54% of the anaesthesia-led trials focused on safety, whereas all (100%) surgery-led trials focused on efficacy (P=0.004). Compared with usual care, mean arterial pressure in controlled hypotension was 23% (95% confidence interval [CI] 17-29%) lower in anaesthesia trials and 30% (95% CI 14-37%) lower in surgery trials; estimated blood loss was 44% (95% CI 30-55%) less in anaesthesia trials and 38% (95% CI 30-49%) less in surgery trials. Overall, blood loss was reduced by 43% (95% CI 32-53%), and trial sequential analysis supported an efficacy conclusion. Mean arterial pressure and estimated blood loss reductions were associated (R2=0.41, P=0.002). All trials were underpowered for safety outcomes, and none adequately evaluated myocardial or renal injury. CONCLUSIONS: Anaesthesia researchers prioritised safety outcomes, whereas surgery researchers emphasised efficacy in controlled hypotension trials. Controlled hypotension significantly reduces blood loss. In contrast, safety outcomes were poorly studied. Given increasing observational evidence linking inadvertent hypotension to myocardial and renal injury, the safety of controlled hypotension remains to be addressed. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023450397).

Characteristics associated with effectiveness in postoperative delirium research: a systematic review of randomised controlled trials with meta-regression and meta-analysis.

BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).

Noradrenaline-induced changes in cerebral blood flow in health, traumatic brain injury and critical illness: a systematic review with meta-analysis.

BACKGROUND: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. METHODS: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness. RESULTS: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis. CONCLUSIONS: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.

Efficacy of sensory-based static balance training on the balance ability, aging attitude, and perceived stress of older adults in the community: a randomized controlled trial.

BACKGROUND: This study explores the effect of sensory-based static balance training on the balance ability, aging attitude, and perceived stress of older adults in the community. It provides a practical basis for the in-depth implementation and revision of the community health management model. METHODS: A randomized controlled intervention study was conducted from 2022 to 2023. A total of 72 older adults were recruited and randomly divided into an intervention group (36 individuals) and a control group (36 individuals). Balance ability (measured by the Short Physical Performance Battery and One Leg Stand Test), aging attitudes, and perceived stress were assessed at baseline and at the 12-week and 24-week follow-ups. Repeated-measures ANOVA and generalized estimating equations were used to compare outcome measures. RESULTS: Sensory-based static balance training was beneficial for balance ability and aging attitude among participants in the intervention group. At the end of the intervention, participants in the intervention group showed significant improvements in SPPB scores and OLST scores compared with the control group (FSPPB = 12.347, P = 0.001, Waldχ2OLST = 45.530, P < 0.001), as well as significant differences in aging attitudes (FAAQ = 18.549, P < 0.001). Multiple comparisons at different time points in the intervention group reveal a significant intervention effect (FSPPB = 29.211, Waldχ2OLST = 80.428, FAAQ = 45.981, all P < 0.05). However, the difference in perceived stress before and after the intervention was not significant (FCPSS = 2.876, P = 0.095). CONCLUSIONS: Sensory-based static balance training significantly improved balance ability and aging attitudes among older adults in the community. The effect on perceived stress among older adults in the community was not significant. TRIAL REGISTRATION: Registered in the Chinese Clinic on 04/06/2022. The registration number is ChiCTR2200060541.

One-step growth of Cu-doped carbon dots in amino-modified carbon nanotube-modified electrodes for sensitive electrochemical detection of BPA.

Copper-doped carbon dots and aminated carbon nanotubes (Cu-CDs/NH2-CNTs) nanocomposites were synthesized by a one-step growth method, and the composites were characterized for their performance. An electrochemical sensor for sensitive detection of bisphenol A (BPA) was developed for using Cu-CDs/NH2-CNTs nanocomposites modified with glassy carbon electrodes (GCE). The sensor exhibited an excellent electrochemical response to BPA in 0.2 M PBS (pH 7.0) under optimally selected conditions. The linear range of the sensor for BPA detection was 0.5-160 µM, and the detection limit (S/N = 3) was 0.13 µM. Moreover, the sensor has good interference immunity, stability and reproducibility. In addition, the feasibility of the practical application of the sensor was demonstrated by the detection of BPA in bottled drinking water and Liu Yang River water.

UAV-Assisted Mobile Edge Computing: Dynamic Trajectory Design and Resource Allocation.

The recent advancements of mobile edge computing (MEC) technologies and unmanned aerial vehicles (UAVs) have provided resilient and flexible computation services for ground users beyond the coverage of terrestrial service. In this paper, we focus on a UAV-assisted MEC system in which the UAV equipped with MEC servers is used to assist user devices in computing their tasks. To minimize the weighted average energy consumption and delay in the UAV-assisted MEC system, a LQR-Lagrange-based DDPG (LLDDPG) algorithm, which jointly optimizes the user task offloading and the UAV trajectory design, is proposed. To be specific, the LLDDPG algorithm consists of three subproblems. The DDPG algorithm is used to address the issue of UAV desired trajectory planning, and subsequently, the LQR-based algorithm is employed to achieve the real-time tracking control of UAV desired trajectory. Finally, the Lagrange duality method is proposed to solve the optimization problem of computational resource allocation. Simulation results indicate that the proposed LLDDPG algorithm can effectively improve the system resource management and realize the real-time UAV trajectory design.

The evaluation of levosimendan in patients with acute myocardial infarction related ventricular septal rupture undergoing cardiac surgery: a prospective observational cohort study with propensity score analysis.

STUDY OBJECTIVE: The purpose of the present study was to evaluate the efficacy of levosimendan in patients with acute myocardial infarction related ventricular septal rupture (AMI-VSR) underwent cardiac surgery. DESIGN: Prospective observational cohort study with propensity score analysis. PATIENTS: There were 261 patients with AMI-VSR in our study. After 1:1 propensity matching, 106 patients (53 levosimendan and 53 control) were selected in the matched cohort. INTERVENTIONS: None. MEASUREMENTS: Patients who received levosimendan were assigned to the levosimendan group (n = 164). The patients who were not received were levosimendan assigned to the control group (n = 97). The levosimendan was initiated immediately after cardiopulmonary bypass. Then, it has been maintained during the postoperative 3 days. The poor outcomes were identified as follows: death and postoperative complications (postoperative stroke, low cardiac output syndromeneeded mechanical circulatory support after surgery, acute kidney injury (≥ stage III), postoperative infection or septic shock, new developed atrial fibrillation or ventricular arrhythmias). MAIN RESULTS: Before matching, the control group had more length of ICU stay (6.69 ± 3.90 d vs. 5.20 ± 2.24 d, p < 0.001) and longer mechanical ventilation time (23 h, IQR: 16-53 h vs. 16 h, IQR: 11-23 h, p < 0.001). Other postoperative outcomes have not shown significant differences between two groups. After matching, no significant difference was found between both groups for all postoperative outcomes. The Kaplan-Meier survivul estimate and log-rank test showed that the 90-day survival had no significant differences between two groups before and after matching. CONCLUSION: Our study found that a low-dose infusion of levosimendan in AMI-VSR patients underwent surgical repair did not associated with positively affect to postoperative outcomes.

Retinoblastoma cell-derived Twist protein promotes regulatory T cell development.

BACKGROUND: The development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist­related protein 1 (Twist) in the Treg development. METHODS: The surgically removed Rb tissues were collected. Rbcs were cultured with CD4+ T cells to assess the role of Rbc-derived Twist in the Treg generation. RESULTS: We found that more than 90% Rbcs expressed Twist. Foxp3+ Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4+ T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-ß-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3+ Tregs showed immune-suppressive function on CD8+ T cell proliferation. CONCLUSIONS: Rbcs express Twist, that induces IL-4+ Foxp3+ Tregs; the latter can inhibit CD8+ cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.

Study of the effects of rabbit scleral fibroblasts on cellular biomechanical properties and MMP-2 expression using two modes of riboflavin/ultraviolet A wave collagen cross-linking.

OBJECTIVE: The aim of this study is to evaluate the cellular biomechanical properties and MMP-2 expression changes in rabbit scleral fibroblasts using two modes of riboflavin and ultraviolet A (UVA) collagen cross-linking (CXL). METHODS: Twenty-four New Zealand white rabbits were randomly divided into two groups, A and B. The left eye was chosen for the experimental group and the right eye for the control group. In group A, the eyes were irradiated for 30 min, with a power density of 3.0 mW/cm2. In group B, the eyes were irradiated for 9 min, with a power density of 10.0 mW/cm2. One week after CXL, full-field electroretinography was performed. Sixty days after CXL, the rabbits were sacrificed, and scleral fibroblasts were extracted from the CXL-treated sclera area and corresponding parts of control sclera and cultured. Cellular biomechanical properties were evaluated using the micropipette aspiration technique, and the MMP-2 protein expression was determined by Western blot analysis. RESULTS: There was no statistical difference in the amplitude and latency of the dark adaptation 3.0 and light adaptation 3.0 between the CXL and control eyes of groups A and B (P > 0.05). Compared with the control groups, the Young's modulus of the fibroblasts and apparent viscosity of the experimental eyes in groups A and B were increased after CXL (P < 0.05), but there was no significant difference between the two groups under different irradiation modes (P > 0.05). The MMP-2 expression in scleral fibroblasts from experimental eyes was significantly higher than that in scleral fibroblasts from control eyes in groups A and B. Under the two different irradiation modes, the MMP-2 expression in the scleral fibroblasts from experimental eyes in group A was significantly higher than that in the scleral fibroblasts from experimental eyes in group B. CONCLUSION: The riboflavin-UVA scleral CXL conducted in two different modes produced no significant side effects on the retina and could strengthen the cell biomechanical properties as well as increase the MMP-2 expression of scleral fibroblasts significantly.

Red mud-metakaolin based cementitious material for remediation of arsenic pollution: Stabilization mechanism and leaching behavior of arsenic in lollingite.

The proper treatment of lollingite is of great significance due to its rapid oxidation leading to release of arsenic into the environment. Herein, a green multi-solid waste geopolymer, consisting of red mud, metakaolin, blast furnace slag, and flue gas desulfurization gypsum, was developed. The obtained red mud-metakaolin-based (RMM) geopolymer demonstrated good arsenic retention capability. The results showed that the replacement of SO42- in ettringite with AsO42- via ion exchange, formation of Ca-As and Fe-As precipitates, and physical encapsulation with aluminosilicate gel were the main mechanisms that prevented the release of arsenic. Further dissolution of ettringite in RMM was alleviated by adding a suitable amount of Ca(OH)2 and controlling the pH of the leachate. TCLP results verified that RMM materials possessed an outstanding ability to stabilize arsenic, with a leaching rate below the permitted value of 5 mg/L for safe disposal. The low leachability of the RMM geopolymers (<0.50 mg/L) is potentially related to the pH buffering capacity of the hydration products at a pH range of 2-5. RMM geopolymers showed a high compressive strength (>15 MPa) and low arsenic leaching concentration (<2.66 mg/L) after 28 days of curing. These results demonstrate the potential of RMM geopolymers to be utilized as an environmentally friendly backfilling cementitious material for sustainable remediation of arsenic pollution.

Optimized Electronic Configuration to Improve the Surface Absorption and Bulk Conductivity for Enhanced Oxygen Evolution Reaction.

The composition and structure are crucial for stabilizing an appropriate electronic configuration (unit eg electron for example) in high-efficiency electrocatalysts for the oxygen evolution reaction (OER). Here, an excellent platform to investigate the roles of the composition and structure in tuning the electron configuration for higher OER efficiency is provided by layered perovskite oxides with subtle variations of composition and structure (doping with 0%, 50%, and 100% cobalt in the Bi7Fe3Ti3O21). The crystal structures were analyzed by X-ray diffraction refinement, and the electronic structures were calculated based on X-ray absorption spectroscopy and magnetization vs temperature plots according to the Curie-Weiss law. The results indicate that the elongation of oxygen octahedra along the c-axis in layered perovskite could stabilize Co ions in the intermediate spin (IS) ( t2g)5( eg)1 state, resulting in dramatically enhanced electronic conductivity and absorption capacity. Subsequently, the OER efficiency of sample with 100% Co was found to be (incredibly) 100 times higher than that of the sample with 0% Co, with the current density increased from 0.13 to 43 mA/cm2 (1.8 V vs reversible hydrogen electrode); the Tafel slope was reduced from 656 to 87 mV/dec; and double-layer capacity enhanced from 174 to 4193 µF/cm2. This work reveals that both the composition and structure should be taken into account to stabilize a suitable electronic structure such as IS Co ions with moderate absorption and benign electronic conductivity for high-efficiency catalysis of the OER.

Daratumumab added to standard of care in patients with newly diagnosed multiple myeloma: A network meta-analysis.

PURPOSE: To investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival endpoints for untreated myeloma, we undertook this meta-analysis. METHODS: We searched published reports that described the activity and safety of daratumumab added to standard of care for untreated myeloma. RESULTS: Six daratumumab trials were identified, covering 5106 subjects. Daratumumab containing combinations for untreated myeloma attained an impressive complete response or better (≥CR) rate of 24%, very good partial response or better (≥VGPR) rate of 67%, overall response rate (ORR) of 92%. Daratumumab added to standard of care significantly improved progression free survival (PFS): the HR for PFS was 0.52 [0.44, 0.61], P < .001. The HR for overall survival (OS) was 0.73 [0.52, 1.04], P = .09. In the network meta-analysis for patients ineligible for autologous stem-cell transplantation (ASCT), DRd regimen produced significant PFS advantage vs other first-line treatments (VMP HR:0.39 P < .001, Rd HR:0.55 P < .001, MPT HR:0.38 P < .001, and MP HR:0.22 P < .001); DVMP regimen also produced significant PFS advantage vs VMP (HR:0.50 P < .001), MPT (HR:0.49 P < .001), and MP (HR:0.28 P < .001). Among these first-line regimens (DRd, DVMP, VMP, Rd, MPT, and MP), DRd regimen had the highest probability to be the best intervention, with 83.4% and 91.0% probability to reach the longest PFS and OS, respectively. Toxicity consisted primarily of myelosuppression. And, the vital non-hematologic adverse events (AEs) were peripheral sensory neuropathy (41% of all grades) and upper respiratory tract infection (39% of all grades). CONCLUSIONS: Daratumumab added to standard of care could produce clinical benefits in newly diagnosed patients with multiple myeloma. DRd and DVMP could be good combination options for those patients ineligible for ASCT.

First case of AML with rare chromosome translocations: a case report of twins.

BACKGROUND: Leukemia is different from solid tumor by harboring genetic rearrangements that predict prognosis and guide treatment strategy. PML-RARA, RUNX1-RUNX1T1, and KMT2A-rearrangement are common genetic rearrangements that drive the development of acute myeloid leukemia (AML). By contrast, rare genetic rearrangements may also contribute to leukemogenesis but are less summarized. CASE PRESENTATION: Here we reported rare fusion genes ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15 in a 47-year-old AML-M4 patient with FLT3 internal tandem duplication (ITD) discovered by whole genome sequencing (WGS) using the patient's healthy sibling as a sequencing control. CONCLUSION: This is, to our knowledge, the first case of AML with fusion gene ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15.

Molecularly imprinted polymers fabricated via Pickering emulsions stabilized solely by food-grade casein colloidal nanoparticles for selective protein recognition.

Novel molecularly imprinted polymers (MIPs) based on denatured casein nanoparticle (DCP)-stabilized Pickering emulsions were developed for the first time. Casein, a phosphoprotein, is the main protein in milk. In this work, DCPs were solely used as Pickering-type interfacial emulsifiers for fabrication of MIPs for the selective recognition of proteins for the first time. DCPs were prepared by acidification and heat denaturation (at 80 °C) of casein. Their dispersions have satisfactory colloidal stability over a wide pH range. The DCPs acted as natural, food-grade, and edible interfacial emulsifiers, and adsorbed at the oil-water interface to form Pickering emulsions. After the polymerization of monomers, the template protein was removed by elution. During the elution, the interfacial DCPs were also removed, allowing more imprinted cavities to become exposed. The interfacial imprinting technology causes nearly all the imprinted sites to locate on the surface of the polymeric material. Therefore, the MIPs obtained exhibit fast rebinding and excellent specific recognition ability toward the analytes. Overall, this work provides a promising method for designing and fabricating natural-protein-based structured emulsions to prepare MIPs and thus offers new insight into protein separation and purification. Graphical Abstract Pickering emulsions stabilized by denatured casein particles.

Synthesis of Size-Tunable Hollow Polypyrrole Nanostructures and Their Assembly into Folate-Targeting and pH-Responsive Anticancer Drug-Delivery Agents.

Chemotherapeutic drugs currently used in clinical settings have high toxicity, low specificity, and short half-lives. Herein, polypyrrole-based anticancer drug nanocapsules were prepared by tailoring the size of the nanoparticles with a template method, controlling drug release by means of an aromatic imine, increasing nanoparticle stability through PEGylation, and improving tumor-cell selectivity by folate mediation. The nanoparticles were characterized by TEM and dynamic light scattering. α-Folate receptor expression levelsof tumor cells and normal cells were investigated by western blot and quantitative polymerase chain reaction analyses. Flow cytometry and fluorescence imaging were used to verify the cell uptake of the different-sized nanoparticles. From the different-sized polypyrrole nanoparticles, the optimally functionalized nanoparticles of 180 nm hydrodynamic diameter were chosen and further usedfor in vitroandin vivotests. The nanoparticles showed excellent biocompatibility and the drug-loaded nanoparticles exhibited effective inhibition of tumor cell growth in vitro. Moreover, the drug-loaded nanoparticles showed substantially enhanced accumulation in tumor regions and effectively inhibitedin vivotumor growth. Furthermore, the nanoparticles showed reduced doxorubicin-induced toxicity andno significant side effects in normal organs of tumor-bearing mice, as measured by body-weight shifts and evaluationof drug distribution. Overall, the functionalized nanoparticles are promising nanocarriers for tumor-targeting drug delivery.

Multifunctional halloysite nanotubes for targeted delivery and controlled release of doxorubicin in-vitro and in-vivo studies.

The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-ß-cyclodextrin (ß-CD-(SH)7) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between ß-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.

A Lift-Off-Tolerant Magnetic Flux Leakage Testing Method for Drill Pipes at Wellhead.

To meet the great needs for MFL (magnetic flux leakage) inspection of drill pipes at wellheads, a lift-off-tolerant MFL testing method is proposed and investigated in this paper. Firstly, a Helmholtz coil magnetization method and the whole MFL testing scheme are proposed. Then, based on the magnetic field focusing effect of ferrite cores, a lift-off-tolerant MFL sensor is developed and tested. It shows high sensitivity at a lift-off distance of 5.0 mm. Further, the follow-up high repeatability MFL probing system is designed and manufactured, which was embedded with the developed sensors. It can track the swing movement of drill pipes and allow the pipe ends to pass smoothly. Finally, the developed system is employed in a drilling field for drill pipe inspection. Test results show that the proposed method can fulfill the requirements for drill pipe inspection at wellheads, which is of great importance in drill pipe safety.

Intracellular delivery of messenger RNA by recombinant PP7 virus-like particles carrying low molecular weight protamine.

BACKGROUND: Cell-penetrating peptides (CPPs) have been widely used as carriers to transport different molecules into living cells, whereas messenger RNAs (mRNAs) have been utilized as target molecules for the prevention and treatment of various diseases. However, the instability of CPPs and mRNAs has limited their application. Bacteriophage PP7 virus-like particles (VLPs) may protect peptides and RNAs from degradation through displaying foreign peptides on their surface and encapsidating RNA linked with the pac site. RESULTS: In this study, the cDNA of the PP7 coat protein single-chain dimer carrying low molecular weight protamine (LMWP) and the cDNA of green fluorescent protein (GFP) were inserted into two multiple cloning sites of pETDuet-1, respectively. PP7 VLPs carrying the LMWP peptide and GFP mRNA were subsequently expressed in Escherichia coli BL21 (DE3) with high yield and thermal stability, and were easily purified. The VLPs were also non-replicative, non-infectious, and non-toxic. Moreover, they penetrated the mouse prostate cancer cells RM-1 after 24 h incubation. Last, PP7 VLPs carrying the LMWP could encapsidate the GFP mRNA, which was translated into mature protein in mammalian cells. CONCLUSIONS: Recombinant PP7 VLPs can be used simultaneously as a targeted delivery vector for both peptides and mRNA due to their abilities to package RNA and display peptides.

Regioselectivity-Tunable Self-1,3-Dipolar [3+3] Cyclizations of Azomethine Ylides To Assemble Dispirooxindole-piperazines.

A series of novel 2,3- or 2,5-dispirooxindole-piperazine ring systems were efficiently constructed through the acid-promoted self-1,3-dipolar [3+3] cyclizations of azomethine ylides derived from isatin with various primary or cyclic secondary amines. Interestingly, the regioselectivity of this self-[3+3] cyclization could be effectively tuned by varying the structural features of substrates. The unprecedented 2,5-dispirooxindole-piperazine skeleton was achieved in good diastereoselectivity by employing 1,2,3,4-tetrahydroisoquinoline, while using pyrrolidine or glycine methyl ester furnished the 2,3-dispirooxindole-piperazine scaffold in excellent diastereoselectivity (only a single isomer formed).