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1.
Orthop Surg ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33942985

RESUMEN

OBJECTIVE: To compare the clinical effects of cervical decompression first, lumbar decompression first, or simultaneous decompression of both lesions in the treatment of tandem spinal stenosis (TSS). METHODS: This is a retrospective analysis. From January 2013 to December 2018, 51 TSS patients underwent our surgery and postoperative investigation. Among the 51 subjects, 27 females and 24 males, aged 49-77 years with an average age of 66.3 ± 6.8, were selected. According to the different operation sequences, all patients were divided into three groups. In simultaneous operation group, five patients underwent cervical and lumbar vertebrae surgery at the same time. In first cervical surgery group, 28 patients underwent cervical vertebra surgery first, followed by lumbar spine surgery after a period of recovery. And in first lumbar surgery group, 18 patients underwent lumbar vertebrae surgery first. The choice for neck surgery is posterior cervical single-door vertebroplasty, the surgery of lumber is plate excision and decompression needle-rod system internal fixation. The outcome measures are visual analogue scale (VAS), Japanese Orthopaedic Association cervical (JOA-C) and lumbar (JOA-L) scores, which were assessed at 3 months and 1 year after the operation by telephone interview. In addition, operative time, estimated blood loss, and hospital stay were also recorded. RESULTS: All the patients in the study had surgery performed successfully by the same group of orthopaedic surgeons. The preoperative VAS scores of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 8.00 ± 1.00, 8.36 ± 0.68, and 8.17 ± 0.71 (P > 0.05). The preoperative JOA-C scores were 7.00 ± 2.35, 6.54 ± 1.53, and 7.83 ± 1.04 (P < 0.05). And the preoperative JOA-L scores were 7.20 ± 2.17, 4.64 ± 2.36, and 5.78 ± 1.22 respectively (P < 0.05). During the final 1-year follow-up, the JOA-C improvement rates of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 85.68% ± 5.44%, 84.27% ± 5.02%, and 83.34% ± 10.25%, respectively (P > 0.05), and the JOA-L improvement rates were 80.04% ± 3.35%, 81.65% ± 3.74%, and 80.21% ± 4.76% (P > 0.05). The difference among them was not statistically significant. In addition, operation time (OP), blood loss (BL), and hospital stay (HS) in the simultaneous operation group were 245.00 ± 5.00 min, 480.00 ± 27.39 mL, and 16.60 ± 0.55 days, respectively. While those parameters in the first cervical surgery group were 342.50 ± 18.18 min, 528.21 ± 43.97 mL, and 22.75 ± 2.15 days, and in the first lumbar surgery group they were 346.11 ± 24.77 min, 519.44 ± 43.99 mL, and 22.89 ± 1.64 days. The average blood loss in simultaneous operation group was less (P > 0.05); meanwhile, the operation time and hospital stay time were significantly shorter in the simultaneous operation group than in the first cervical surgery group and first lumbar surgery group (P < 0.05). Only one case of fat liquefaction occurred in first cervical surgery group, which healed spontaneously after a regular change of dressing for 1 month. CONCLUSIONS: Under the condition of ensuring the surgical effect, the choice of staged surgery or concurrent surgery according to the patients' own symptoms of cervical and lumbar symptoms could both obtain satisfactory results, and the damage of simultaneous surgery was less than that of staged surgery.

2.
Light Sci Appl ; 10(1): 94, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33931580

RESUMEN

Solar-blind ultraviolet (UV) photodetectors (PDs) have attracted tremendous attention in the environmental, industrial, military, and biological fields. As a representative III-nitride material, AlGaN alloys have broad development prospects in the field of solar-blind detection due to their superior properties, such as tunable wide bandgaps for intrinsic UV detection. In recent decades, a variety of AlGaN-based PDs have been developed to achieve high-precision solar-blind UV detection. As integrated optoelectronic technology advances, AlGaN-based focal plane arrays (FPAs) are manufactured and exhibit outstanding solar-blind imaging capability. Considering the rapid development of AlGaN detection techniques, this paper comprehensively reviews the progress on AlGaN-based solar-blind UV PDs and FPAs. First, the basic physical properties of AlGaN are presented. The epitaxy and p-type doping problems of AlGaN alloys are then discussed. Diverse PDs, including photoconductors and Schottky, metal-semiconductor-metal (MSM), p-i-n, and avalanche photodiodes (APDs), are demonstrated, and the physical mechanisms are analyzed to improve device performance. Additionally, this paper summarizes imaging technologies used with AlGaN FPAs in recent years. Benefiting from the development of AlGaN materials and optoelectronic devices, solar-blind UV detection technology is greeted with significant revolutions. Summarizing recent advances in the processing and properties of AlGaN-based solar-blind UV PDs and FPAs as well as AlGaN growth and doping techniques.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33949062

RESUMEN

Nature segregates fundamental tasks such as information storage/transmission and catalysis between two different compound classes (e.g. polynucleotides for replication and folded polyamides for catalysis). This division of labor is likely a product of evolution, raising the question of how simpler systems in which replicators and folded macromolecules co-exist may emerge in the transition from chemistry to biology. In synthetic systems, achieving co-existence of replicators and foldamers in a single molecular network remains an unsolved problem. Previous work on dynamic molecular networks has given rise to either self-replicating fibers or well-defined foldamer structures (or completely un-sorted complex systems). We report a system in which two cross-reactive dithiol (nucleobase- and peptide-based) building blocks self-sort into a replicator fiber and foldamer that both emerge spontaneously and co-exist. The self-sorting behavior remains prevalent across different building block ratios as two phases of emergence occur: replicator growth followed by foldamer formation. This is attributed to the autocatalytic formation of the replicator fiber, followed by enrichment of the system in the remaining building block, which is subsequently incorporated into a foldamer.

4.
Adv Healthc Mater ; : e2100109, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33949138

RESUMEN

Cartilage damage is a prevalent health concern among humans. The inertness of cartilage, the absence of self-healing properties, and the lack of appropriate repair materials that integrate into the tissue pose a significant challenge for cartilage repair. Thus, it is important to develop novel soft biomaterials with strong tissue adhesion and chondrogenic capabilities for cartilage repair. Herein, a new type of protein adhesive is reported that exhibits superior cartilage repair performance. The material is fabricated by the electrostatic combination of chondroitin sulfate (CS) and positively charged elastin-like protein, which is derived from natural components of the extracellular matrix (ECM). The adhesive showed robust adhesion properties on different tissue substrates, offering a favorable environment for cartilage tissue integration. Noncovalent bonding between CS molecules in the glue allows for its controlled release, which is required for efficient chondrogenic differentiation. When implanted into a rat model of cartilage defect, this protein adhesive exhibited beneficial healing effects, as evidenced by enhanced chondrogenesis, sufficient ECM production, and lateral integration. Therefore, this engineered protein complex is a promising candidate for translational application in the field of cartilage repair.

5.
ACS Nano ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33818058

RESUMEN

The highest quality hexagonal boron nitride (hBN) crystals are grown from molten solutions. For hBN crystal growth at atmospheric pressure, typically the solvent is a combination of two metals, one with a high boron solubility and the other to promote nitrogen solubility. In this study, we demonstrate that high-quality hBN crystals can be grown at atmospheric pressure using pure iron as a flux. The ability to produce excellent-quality hBN crystals using pure iron as a solvent is unexpected, given its low solubility for nitrogen. The properties of crystals produced with this flux matched the best values ever reported for hBN: a narrow Raman E2g vibration peak (7.6 cm-1) and strong phonon-assisted peaks in the photoluminescence spectra. To further test their quality, the hBN crytals were used as a substrate for WSe2 epitaxy. WSe2 was deposited with a low nucleation density, indicating the low defect density of the hBN. Lastly, the carrier tunneling through our hBN thin layers (3.5 nm) follows the Fowler-Nordheim model, with a barrier height of 3.7 eV, demonstrating hBN's superior electrical insulating properties. This ability to produce high-quality hBN crystals in such a simple, environmentally friendly and economical process will advance two-dimensional material research by enabling integrated devices.

6.
Can J Gastroenterol Hepatol ; 2021: 6677821, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791254

RESUMEN

Purpose. To compare the diagnostic value of texture analysis- (TA-) derived parameters from out-of-phase T1W, in-phase T1W, and T2W images in the classification of the early stage of liver fibrosis. Methods. Patients clinically diagnosed with hepatitis B infection, who underwent liver biopsy and noncontrast MRI scans, were enrolled. TA parameters were extracted from out-of-phase T1-weighted (T1W), in-phase T1W, and T2-weighted (T2W) images and calculated using Artificial Intelligent Kit (AK). Features were extracted including first-order, shape, gray-level cooccurrence matrix, gray-level run-length matrix, neighboring gray one tone difference matrix, and gray-level differential matrix. After statistical analyses, final diagnostic models were constructed. Receiver operating curves (ROCs) and areas under the ROC (AUCs) were used to assess the diagnostic value of each final model and 100-time repeated cross-validation was applied to assess the stability of the logistic regression models. Results. A total of 57 patients were enrolled in this study, with 27 in the fibrosis stage < 2 and 30 in stages ≥ 2. Overall, 851 features were extracted per ROI. Eight features with high correlation were selected by the maximum relevance method in each sequence, and all had a good diagnostic performance. ROC analysis of the final models showed that all sequences had a preferable performance with AUCs of 0.87, 0.90, and 0.96 in T2W and in-phase and out-of-phase T1W, respectively. Cross-validation results reported the following values of mean accuracy, specificity, and sensitivity: 0.98 each for out-of-phase T1W; 0.90, 0.89, and 0.90 for in-phase T1W; and 0.86, 0.88, 0.84 for T2W in the training set, and 0.76, 0.81, and 0.72 for out-of-phase T1W; 0.74, 0.72, and 0.75 for in-phase T1W; and 0.63, 0.64, and 0.63 for T2W for the test group, respectively. Conclusion. Noncontrast MRI scans with texture analysis are viable for classifying the early stages of liver fibrosis, exhibiting excellent diagnostic performance.

7.
Phytother Res ; 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33792976

RESUMEN

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

8.
Huan Jing Ke Xue ; 42(5): 2402-2412, 2021 May 08.
Artículo en Chino | MEDLINE | ID: mdl-33884811

RESUMEN

The process parameters and sludge properties of an in-situ sludge ozone-reduction system were investigated under different ozone dosages and sludge ages. Subsequently, 75 mg·g-1 (as O3/MLVSS) was selected as the appropriate ozone dosage to satisfy the wastewater treatment capacity and in-situ sludge ozone-reduction. The calibration coefficient results of the sludge yield formula indicated that Yh was reduced from 0.331 g·g-1 to 0.326 g·g-1 (to MLVSS/COD m) by ozone treatment and Kd was increased from 0.046 d-1 to 0.050 d-1 at 75 mg·g-1. The effluent quality of the SBR system was satisfactory when the sludge age was 10 d. The ozone dosage of 75 mg·g-1 and sludge age of 10 d were selected as the appropriate process conditions, at which the excess sludge was reduced by 12%. The high-throughput sequencing results concluded that the microorganisms in the excess sludge after ozonation were different in phylum and genus. After ozone treatment, the abundance of Bacteroidetes increased by 1.2 times and the relative abundance of Proteobacteria with nitrification and denitrification ability decreased from 24% to 18%. The reduction in the abundance of nitrobacteria affected the denitrification capacity of the sewage treatment system, but the total effluent nitrogen still met the I B discharge standard of pollutants for municipal wastewater treatment plants. The relative abundance of Lactococcus increased from 0.4% to 21.6%. Simultaneously, the concentration of macromolecular organic substances in the EPS of the excess sludge increased from 40.6 mg·g-1 to 54.6 mg·g-1, while the CST increased from 15 s to 17 s after ozone treatment. The zeta potential decreased from -10.04 mV to -15.20 mV and the SVI of the excess sludge increased from 54 mL·g-1 to 62 mL·g-1, thereby indicating that the sedimentation performance and dewaterability were affected to some extent. However, the SS of the effluent and the solids content of the sludge cake after extraction did not change significantly, the system could still operate stably, and the subsequent dewaterability of the excess sludge was not significantly affected.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33887096

RESUMEN

Maximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer-cell-specific or even cancer-cell-organelle-specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo , which is difficult to achieve. Herein, we report a strategy of cancer-cell-activated PS synthesis, by which an efficient mitochondria-targeting photosensitizer with aggregation-induced-emission (AIE) feature can be selectively synthesized as an efficient image-guided PDT agent inside cancer cells. MOF-199, a Cu(II)-based metal-organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a Cu(I) catalyst source for in-situ click reaction to form PSs exclusively in cancer cells. The in-situ synthesized PS showed mitochondria-targeting capability, allowing potent cancer-cell-specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post-treatment.

10.
Pharmacol Res ; : 105628, 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33887437

RESUMEN

Extracellular vesicles are composed of loaded soluble substances and lipid bilayers; these include apoptotic bodies, exosomes, and microvesicles. Extracellular vesicles, as carriers of biological information between cells, have been recognized for their role in the diagnosis and treatment of cardiovascular diseases. The biogenesis of extracellular vesicles is closely related to autophagy. Moreover, extracellular vesicles further affect autophagy levels in target cells through their transmitted contents. Autophagy is a catabolic cell process that maintains cell homeostasis by eliminating misfolded proteins and damaged organelles. Existing studies have revealed that extracellular vesicles and autophagy share molecular mechanisms with notable crosstalk, including, perspectives such as amphisomes and "secretory autophagy." In this review, we first introduce the biogenesis of extracellular vesicles and the classic views of autophagy before moving onto the crosstalk between extracellular vesicles and autophagy. Finally, we discuss the research progress of extracellular vesicles and autophagy in cardiovascular pathophysiology.

11.
Ann Thorac Surg ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33819473

RESUMEN

BACKGROUND: The study aimed to compare the safety and effectiveness between fenestrated technique with or without chimney stent and single-branched stent-graft for isolated left subclavian artery (LSA) revascularization during endovascular repair of acute type B aortic dissection (ATBAD) with unfavorable proximal landing zone. METHODS: From January 2016 to December 2019, 65 ATBAD patients with unfavorable proximal landing zone were treated with either the fenestrated technique (n=34, group A) or single-branched stent-graft (n=31, group B). Type I endoleak, retrograde type A dissection, stroke, LSA patency, 30-day mortality, and aortic remodeling were systematically recorded and retrospectively analyzed. RESULTS: Technical success rates for groups A and group B were 94.12% and 100%, respectively. LSA primary patency was achieved for all enrolled patients. The incidence of type I endoleak, retrograde type A dissection, stroke, and 30-day mortality was 5.9%, 5.9%, 2.9%, and 2.9% in group A, respectively, but none were encountered in group B. LSA Occlusion was observed in three and two patients during a mean follow-up of 16.18±2.08 and 15.19±2.68 months in groups A and B, respectively. After the procedure, significant aortic remodeling was detected in both groups during follow-up. CONCLUSIONS: Both techniques are feasible and safe for isolated LSA revascularization during endovascular repair for ATBAD. Apart from the associated perioperative risks of complications and mortality for the fenestrated technique, both procedures contributed to favorable aortic remodeling.

12.
Cancer Res ; 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33853830

RESUMEN

LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). While treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited. Here we report that loss of LKB1 results in increased secretion of the C-X-C motif (CXC) chemokines with an NH2-terminal Glu-Leu-Arg (ELR) motif in premalignant and cancerous cells, as well as in genetically engineered murine models (GEMM) of NSCLC. Heightened levels of ELR+ CXC chemokines in LKB1-deficient murine models of NSCLC positively correlated with increased abundance of granulocytic myeloid-derived suppressor cells (G-MDSC) locally within the tumor microenvironment and systemically in peripheral blood and spleen. Depletion of G-MDSCs with antibody or functional inhibition via all-trans-retinoic acid (ATRA) led to enhanced anti-tumor T cell responses and sensitized LKB1-deficent murine tumors to PD-1 blockade. Combination therapy with anti-PD-1 and ATRA improved local and systemic T cell proliferation and generated tumor-specific immunity. Our findings implicate ELR+ CXC chemokine-mediated enrichment of G-MDSCs as a potential mediator of immunosuppression in LKB1-deficient NSCLC and provide a rationale for utilizing ATRA in combination with anti-PD-1 therapy in patients with LKB1-deficient NSCLC refractory to ICIs.

13.
Sci Rep ; 11(1): 7999, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33846492

RESUMEN

To assess the influence of lipid-lowering therapy on coronary plaque volume, and to identify the LDL and HDL targets for plaque regression to provide a comprehensive overview. The databases searched (from inception to 15 July 2020) to identify prospective studies investigating the impact of lipid-lowering therapy on coronary plaque volume and including quantitative measurement of plaque volume by intravascular ultrasound after treatment. Thirty-one studies that included 4997 patients were selected in the final analysis. Patients had significantly lower TAV (SMD: 0.123 mm3; 95% CI 0.059, 0.187; P = 0.000) and PAV (SMD: 0.123%; 95% CI 0.035, 0.212; P = 0.006) at follow-up. According to the subgroup analyses, TAV was significantly reduced in the LDL < 80 mg/dL and HDL > 45 mg/dL group (SMD: 0.163 mm3; 95% CI 0.092, 0.234; P = 0.000), and PAV was significantly reduced in the LDL < 90 mg/dL and HDL > 45 mg/dL group (SMD: 0.186%; 95% CI 0.081, 0.291; P = 0.001).Thirty-one studies that included 4997 patients were selected in the final analysis. Patients had significantly lower TAV (SMD: 0.123 mm3; 95% CI 0.059, 0.187; P = 0.000) and PAV (SMD: 0.123%; 95% CI 0.035, 0.212; P = 0.006) at follow-up. According to the subgroup analyses, TAV was significantly reduced in the LDL < 80 mg/dL and HDL > 45 mg/dL group (SMD: 0.163 mm3; 95% CI 0.092, 0.234; P = 0.000), and PAV was significantly reduced in the LDL < 90 mg/dL and HDL > 45 mg/dL group (SMD: 0.186%; 95% CI 0.081, 0.291; P = 0.001). Our meta-analysis suggests that not only should LDL be reduced to a target level of < 80 mg/dL, but HDL should be increased to a target level of > 45 mg/dL to regress coronary plaques.Trial Registration PROSPERO identifier: CRD42019146170.

14.
Adv Mater ; : e2100619, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33861490

RESUMEN

Surgical excision is the main choice for tongue cancer treatment. However, the physiological functions of oral and maxillofacial regions might be severely impaired and high risk of tongue tumor recurrence cannot be avoided. It is thus becoming urgently important to develop alternative strategies for tongue cancer therapy. In this regard, a new class of near-infrared (NIR) light-responsive and peritumoral injectable hydrogel is fabricated with extraordinary photothermal therapy (PTT) for in situ tongue tumors. The as-prepared soft material exhibits good biocompatibility and ultra-strong photothermal effect due to the formed network by negatively charged proteins, chitosan molecules, and Ag3 AuS2 nanoparticles (NPs). In a well-constructed in situ tongue tumor model, tumors can be efficiently eradicated by one-time PTT treatment. Importantly, there are no side effects on surrounding normal tissues and potential tumor recurrence is inhibited. In stark contrast to traditional surgical excision, such biomaterials hold great potential for clinical treatment of oral cancers.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 256: 119735, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-33819759

RESUMEN

Hypochlorite (HClO/ClO-), an important reactive oxygen species (ROS), plays a significant role in the human immune system. Thus, developing a fast and efficient method for detecting ClO- is quite necessary. Herein, we designed and synthesized a fluorescent probe TPB-CN based on twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) characteristics. The probe could respond to ClO- with an ultrafast response velocity (<2 s). The detection limit was calculated to be 6.198 nM. In addition, probe TPB-CN was successfully applied for detecting ClO- in living cells and mouse.

16.
Materials (Basel) ; 14(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807405

RESUMEN

We investigated H2O molecule adsorption that had an effect on the luminescence properties of the CsI(Na) crystal using experiments and first-principle calculations. We measured the emission spectra of the CsI(Na) crystal at different exposure times under gamma ray excitation. The experimental results showed that the energy resolution of the CsI(Na) crystal was worse when the crystal surface adsorbed more H2O molecules, and the crystal surface deliquescence decreased the luminescence efficiency of the CsI(Na) crystal. We studied the band structure, density of states, and optical properties changes caused by H2O molecule adsorption on the CsI(Na) (010) surface. The generalized gradient approximation (GGA) was used to describe the exchange and correlation potential between the electrons. Our calculation results showed that the band gap width of the CsI(Na) (010) surface decreased after adsorbing H2O molecules, while three new peaks appeared in the valence band, and the absorption coefficient decreased from 90,000 cm-1 to 65,000 cm-1, and the reflection coefficient decreased from 0.195 to 0.105. Further, the absorption coefficient was reduced by at least 25% because of H2O molecule adsorption, which led to the luminescence degradation of the CsI(Na) crystal.

17.
Cancer Discov ; 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33839689

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic KRAS mutations prevail in 95% of PDAC tumors and co-occur with genetic alterations in the TP53 tumor suppressor in nearly 70% of patients. Most TP53 alterations are missense mutations that exhibit gain-of-function phenotypes that include increased invasiveness and metastasis yet the extent of direct cooperation between KRAS effectors and mutant p53 remains largely undefined. We show that oncogenic KRAS effectors activate cyclic AMP responsive element binding protein 1 (CREB1) to allow physical interactions with mutant p53 that hyperactivate multiple pro-metastatic transcriptional networks. Specifically, mutant p53 and CREB1 upregulate the pro-metastatic, pioneer transcription factor, FOXA1, activating its transcriptional network while promoting Wnt/B-catenin signaling, together driving PDAC metastasis. Pharmacologic CREB1 inhibition dramatically reduced FOXA1 and B-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic KRAS and mutant p53 to mitigate metastasis.

18.
Stem Cell Res Ther ; 12(1): 224, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33820561

RESUMEN

BACKGROUND: Exosomes derived from the bone marrow mesenchymal stem cell (MSC) have shown great potential in spinal cord injury (SCI) treatment. This research was designed to investigate the therapeutic effects of miR-26a-modified MSC-derived exosomes (Exos-26a) following SCI. METHODS: Bioinformatics and data mining were performed to explore the role of miR-26a in SCI. Exosomes were isolated from miR-26a-modified MSC culture medium by ultracentrifugation. A series of experiments, including assessment of Basso, Beattie and Bresnahan scale, histological evaluation, motor-evoked potential recording, diffusion tensor imaging, and western blotting, were performed to determine the therapeutic influence and the underlying molecular mechanisms of Exos-26a in SCI rats. RESULTS: Exos-26a was shown to promote axonal regeneration. Furthermore, we found that exosomes derived from miR-26a-modified MSC could improve neurogenesis and attenuate glial scarring through PTEN/AKT/mTOR signaling cascades. CONCLUSIONS: Exosomes derived from miR-26a-modified MSC could activate the PTEN-AKT-mTOR pathway to promote axonal regeneration and neurogenesis and attenuate glia scarring in SCI and thus present great potential for SCI treatment.

19.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(2): 200-204, 2021 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-33825382

RESUMEN

OBJECTIVE: This paper introduces the key content and background of Technical Review Guidance for the Registration of Personalized Additive Manufacturing Medical Devices of Passive Implantable Bone, Joint and Oral Hard Tissues. METHODS: The core contents and importance of the construction of personalized design validation and verification and additive manufacturing system are described respectively. RESULTS: The personalized design needs to be carried out under the control of interactive cooperation between healthcare professional and engineer. And the performance of personalized device must be validated and verified completely. At the same time, in view of the particularity of the quality management system of additive manufacturing, the technical focus is expounded. CONCLUSIONS: New ideas and methods shall be used in evaluate and administrate personalized additive manufacturing medical device.


Asunto(s)
Impresión Tridimensional , Prótesis e Implantes
20.
Artículo en Inglés | MEDLINE | ID: mdl-33835669

RESUMEN

Ferroptosis regulates cell death through reactive oxygen species associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of LD and nucleus dual-targeted ratiometric fluorescent probe of CQPP for monitoring polarity change in cellular microenvironment. Due to the appropriate donor-acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals to polarity variations. Using nucleus imaging as a reference, CQPP has been successfully applied to report the increase in LD polarity, the homogenization of polarity in LDs and cytoplasm in the ferroptosis model. This LD and nucleus dual-targeted fluorescent probe shows great potential of using fluorescence imaging to study ferroptosis and ferroptosis-related diseases.

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