ABSTRACT
Reduced glutathione (GSH) is widely used as an antioxidant in clinical practice, but whether GSH affects the development of early lung cancer remains unclear. Herein, we investigated the mechanism underlying the anticancer effect of GSH in patients with pulmonary nodules. Thirty patients with pulmonary nodules were treated with GSH intravenously for 10â¯days at a dose of 1.8â¯g/d, followed by oral administration of the drug at a dose of 0.4â¯g three times daily for 6â¯months. The results showed that GSH treatment promoted nodule absorption and reduced the IL-6 level in the peripheral blood of the patients. GSH reduced IL-6 expression in inflammatory BEAS-2B and lung cancer cells and inhibited the proliferation of lung cancer cell lines in vitro. In addition, GSH reduced IL-6 expression by decreasing ROS via down-regulating PI3K/AKT/FoxO pathways. Finally, GSH reversed the Warburg effect, restored mitochondrial function, and reduced the IL-6 expression via PI3K/AKT/FoxO pathways. The in vivo experiment confirmed that GSH inhibited lung cancer growth, improved mitochondrial function, and reduced the IL-6 expression by regulating key enzymes via the PI3K/AKT/FoxO pathway. In conclusion, we uncovered that GSH exerts an unprecedentedly potent anti-cancer effect to prevent the transformation of lung nodules to lung cancer by improving the mitochondrial function and suppressing inflammation via PI3K/AKT/FoxO pathway. This investigation innovatively positions GSH as a potentially safe and efficacious old drug with new uses, inhibiting inflammation and early lung cancer. The use of the drug offers a promising preventive strategy when administered during the early stages of lung cancer.
ABSTRACT
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with high morbidity and mortality rates. The aims of this study were to investigate the immune-promoting action of nucleolar and spindle-associated protein 1 (NUSAP1) and identify an immunotherapy target for HCC. The Cancer Genome Atlas (TCGA) was used to analyze interaction molecules and immune correlation. The interaction between NUSAP1 and SHC binding and spindle associated 1 (SHCBP1) was examined. The role of the SHCBP1/Janus kinase 2/signal transducer and activator of transcription 3 (SHCBP1/JAK2/STAT3) pathway in this process was explored. After co-culture with HCC cell lines, the differentiation of peripheral blood mononuclear cells (PBMCs) into dendritic cells (DC) was evaluated by measuring the expression of surface factors CD1a and CD86. Pathological tissues from 50 patients with HCC were collected to validate the results of cell experiments. The expression levels of CD1a and CD86 in tissues were also determined. The results show that NUSAP1 interacted with SHCBP1 and was positively correlated with DC. In HCC cell lines, an interaction was observed between NUSAP1 and SHCBP1. It was verified that NUSAP1 inhibited the JAK2/STAT3 phosphorylation pathway by blocking SHCBP1. After co-culture, the levels of CD1a and CD86 in PBMC were elevated. In the clinical specimens, CD1a and CD86 expression levels were significantly higher in the high-NUSAP1 group versus the low-NUSAP1 group. In Summary, NUSAP1 enhanced immunity by inhibiting the SHCBP1/JAK2/STAT3 phosphorylation pathway and promoted DC generation and HCC apoptosis. NUSAP1 may be a target of immunotherapy for HCC.
ABSTRACT
Purpose: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI). Methods: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed. Results: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras. Conclusion: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.
Subject(s)
Antineoplastic Agents , Cisplatin , Folic Acid , Liposomes , Magnetic Resonance Imaging , Ovarian Neoplasms , Polyethylene Glycols , Female , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/therapy , Liposomes/chemistry , Cisplatin/pharmacology , Cisplatin/chemistry , Cisplatin/administration & dosage , Cisplatin/pharmacokinetics , Animals , Folic Acid/chemistry , Folic Acid/pharmacology , Folic Acid/pharmacokinetics , Humans , Magnetic Resonance Imaging/methods , Polyethylene Glycols/chemistry , Cell Line, Tumor , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Mice , Platinum/chemistry , Platinum/pharmacology , Hyperthermia, Induced/methods , Nanocomposites/chemistry , Mice, Nude , Mice, Inbred BALB C , Metal Nanoparticles/chemistry , Magnetic Fields , Particle SizeABSTRACT
Introduction: Fused in sarcoma (FUS) mutations represent the most common genetic etiology of juvenile amyotrophic lateral sclerosis (JALS), for which effective treatments are lacking. In a prior report, we identified a novel FUS mutation, c.1509dupA: p. R503fs (FUSR503fs), in a sporadic JALS patient. Methods: The physicochemical properties and structure of FUSR503fs protein were analyzed by software: Multi-electrode array (MEA) assay, calcium activity imaging assay and transcriptome analysis were used to explore the pathophysiological mechanism of iPSC derived motor neurons. Results: Structural analysis and predictions regarding physical and chemical properties of this mutation suggest that the reduction of phosphorylation and glycosylation sites, along with alterations in the amino acid sequence, may contribute to abnormal FUS accumulation within the cytoplasm and nucleus of induced pluripotent stem cell- derived motor neurons (MNs). Multi-electrode array and calcium activity imaging indicate diminished spontaneous electrical and calcium activity signals in MNs harboring the FUSR503fs mutation. Transcriptomic analysis reveals upregulation of genes associated with viral infection and downregulation of genes involved in neural function maintenance, such as the ATP6V1C2 gene. Treatment with ropinirole marginally mitigates the electrophysiological decline in FUSR503fs MNs, suggesting the utility of this cell model for mechanistic exploration and drug screening. Discussion: iPSCs-derived motor neurons from JALS patients are promising tools for drug screening. The pathological changes in motor neurons of FUSR503fs may occur earlier than in other known mutation types that have been reported.
ABSTRACT
The unique 1D crystal structure of Antimony Triselenide (Sb2Se3) offers notable potential for use in flexible, lightweight devices due to its excellent bending characteristics. However, fabricating high-efficiency flexible Sb2Se3 solar cells is challenging, primarily due to the suboptimal contact interface between the embedded Sb2Se3 layer and the molybdenum back-contact, compounded by complex intrinsic defects. This study introduces a novel Molybdenum Trioxide (MoO3) interlayer to address the back contact interface issues in flexible Sb2Se3 devices. Further investigations indicate that incorporating a MoO3 interlayer not only enhances the crystalline quality but also promotes a favorable [hk1] growth orientation in the Sb2Se3 absorber layer. It also reduces the barrier height at the back contact interface and effectively passivates harmful defects. As a result, the flexible Sb2Se3 solar cell, featuring a Mo-foil/Mo/MoO3/Sb2Se3/CdS/ITO/Ag substrate structure, demonstrates exceptional flexibility and durability, enduring large bending radii and multiple bending cycles while achieving an impressive efficiency of 8.23%. This research offers a straightforward approach to enhancing the performance of flexible Sb2Se3 devices, thereby expanding their application scope in the field of photovoltaics.
ABSTRACT
Antimony triselenide (Sb2 Se3 ) has possessed excellent optoelectronic properties and has gained interest as a light-harvesting material for photovoltaic technology over the past several years. However, the severe interfacial and bulk recombination obviously contribute to significant carrier transport loss thus leading to the deterioration of power conversion efficiency (PCE). In this work, buried interface and heterojunction engineering are synergistically employed to regulate the film growth kinetic and optimize the band alignment. Through this approach, the orientation of the precursor films is successfully controlled, promoting the preferred orientational growth of the (hk1) of the Sb2 Se3 films. Besides, interfacial trap-assisted nonradiative recombination loss and heterojunction band alignment are successfully minimized and optimized. As a result, the champion device presents a PCE of 9.24% with short-circuit density (JSC ) and fill factor (FF) of 29.47 mA cm-2 and 63.65%, respectively, representing the highest efficiency in sputtered-derived Sb2 Se3 solar cells. This work provides an insightful prescription for fabricating high-quality Sb2 Se3 thin film and enhancing the performance of Sb2 Se3 solar cells.
ABSTRACT
Sodium-ion batteries (SIBs) have garnered extensive attentions in recent years as a low-cost alternative to lithium-ion batteries. However, achieving both high capacity and long cyclability in cathode materials remains a challenge for SIB commercialization. P3-type Na0.67Ni0.33Mn0.67O2 cathodes exhibit high capacity and prominent Na+ diffusion kinetics but suffer from serious capacity decay and structural deterioration due to stress accumulation and phase transformations upon cycling. In this work, a dual modification strategy with both morphology control and element doping is applied to modify the structure and optimize the properties of the P3-type Na0.67Ni0.33Mn0.67O2 cathode. The modified Na0.67Ni0.26Cu0.07Mn0.67O2 layered cathode with hollow porous microrod structure exhibits an excellent reversible capacity of 167.5 mAh g-1 at 150 mA g-1 and maintains a capacity above 95 mAh g-1 after 300 cycles at 750 mA g-1. For one thing, the specific morphology shortens the Na+ diffusion pathway and releases stress during cycling, leading to excellent rate performance and high cyclability. For another, Cu doping at the Ni site reduces the Na+ diffusion energy barrier and mitigates unfavorable phase transitions. This work demonstrates that the electrochemical performance of P3-type cathodes can be significantly improved by applying a dual modification strategy, resulting in reduced stress accumulation and optimized Na+ migration behavior for high-performance SIBs.
ABSTRACT
Background: To design a vascular pedicled fascia-prosthesis compound model that can be used for ear reconstruction surgery. Methods: A vascularized tissue engineering chamber model was constructed in New Zealand rabbits, and fresh tissues were obtained after 4 weeks. The histomorphology and vascularization of the newly born tissue compound were analyzed and evaluated by tissue staining and Micro-CT scanning. Results: The neoplastic fibrous tissue formed in the vascularized tissue engineering chamber with the introduction of abdominal superficial vessels, similar to normal fascia, was superior to the control group in terms of vascularization, vascular density, total vascular volume, and total vascular volume/total tissue volume. Conclusion: In vivo, introducing abdominal superficial vessels in the tissue engineering chamber prepped for ear prosthesis may form a well-vascularized pedicled fascia-prosthesis compound that can be used for ear reconstruction.
ABSTRACT
Layered transition metal oxides are promising cathode materials for sodium-ion batteries due to their high energy density and appropriate operating potential. However, the poor structural stability is a major drawback to their widespread application. To address this issue, B3+ is successfully introduced into the tetrahedral site of Na0.67 Fe0.5 Mn0.5 O2 , demonstrating the effectiveness of small-radius ion doping in improving electrochemical performance. The obtained Na0.67 Fe0.5 Mn0.5 B0.04 O2 exhibits excellent cycling performance with 88.8% capacity retention after 100 cycles at 1 C and prominent rate performance. The structure-property relationship is constructed subsequently by neutron powder diffraction, in situ X-ray diffraction and X-ray absorption spectroscopy, which reveal that the Jahn-Teller distortion and the consequent P2-P2' phase transformation are effectively mitigated because of the occupancy of B3+ at the interstitial site. Furthermore, it is found that the transition metal layers are stabilized and the transition metal dissolution are suppressed, resulting in excellent cycling performance. Besides, the prominent rate performance is attributed to the enhanced diffusion kinetics associated with the rearrangement of Na+ . This work provides novel insight into the action mechanism of interstitial site doping and demonstrates a universal approach to improve the electrochemical properties of P2-type manganese-based sodium cathode materials.
ABSTRACT
Antimony selenide (Sb2Se3) is emerging as a promising photovoltaic material owing to its excellent photoelectric property. However, the low carrier transport efficiency, and detrimental surface oxidation of the Sb2Se3 thin film greatly influenced the further improvement of the device efficiency. In this study, the introduction of tellurium (Te) can induce the benign growth orientation and the desirable Sb/Se atomic ratio in the Te-Sb2Se3 thin film. Under various characterizations, it found that the Te-doping tended to form Sb2Te3-doped Sb2Se3, instead of alloy-type Sb2(Se,Te)3. After Te doping, the mitigation of surface oxidation has been confirmed by the Raman spectra. High-quality Te-Sb2Se3 thin films with preferred [hk1] orientation, large grain size, and low defect density can be successfully prepared. Consequently, a 7.61% efficiency Sb2Se3 solar cell has been achieved with a VOC of 474 mV, a JSC of 25.88 mA/cm2, and an FF of 64.09%. This work can provide an effective strategy for optimizing the physical properties of the Sb2Se3 absorber, and therefore the further efficiency improvement of the Sb2Se3 solar cells.
ABSTRACT
As a potential substitute for lithium-ion battery, sodium-ion batteries (SIBs) have attracted a tremendous amount of attention due to their advantages in terms of cost, safety and sustainability. Nevertheless, further improvement of the energy density of cathode materials in SIBs remains challenging and requires the activation of anion redox reaction (ARR) activity to provide additional capacity. Herein, we report a high-performance Mn-based sodium oxide cathode material, Na0.67Mg0.1Zn0.1Mn0.8O2 (NMZMO), with synergistic activation of ARR by cosubstitution. This material can deliver an ultra-high capacity of â¼233 mAh/g at 0.1 C, which is significantly higher than their single-cation-substituted counterparts and among the best in as-reported MgMn or ZnMn-based cathodes. Various spectroscopic techniques were comprehensively employed and it was demonstrated that the higher capacity of NMZMO originated from the enhanced ARR activity. Neutron pair distribution function and resonant inelastic X-ray scattering experiments revealed that out-of-plane migration of Mg/Zn occurred upon charging and oxygen anions in the form of molecular O2 were trapped in vacancy clusters in the fully-charged-state. In NMZMO, Mg and Zn mutually interacted with each other to migrate toward tetrahedral sites, which provided a prerequisite for further ARR activity enhancement to form more trapped molecular O2. These findings provide unique insight into the ARR mechanism and can guide the development of high-performance cathode materials through ARR enhancement strategies.
Subject(s)
Electric Power Supplies , Oxides , Oxidation-Reduction , Ions , Electrodes , OxygenABSTRACT
Objective: This study aimed to evaluate the treatment response, survival profiles, prognostic factors and adverse events of anlotinib in treating advanced non-small cell lung cancer (NSCLC) patients. Materials and Methods: Totally, 158 advanced NSCLC patients were included in this retrospective study. All patients received anlotinib treatment until disease progression or intolerance: Administrated orally 12 mg/d for 2 weeks then discontinued for 1 week (3 weeks as a treatment cycle). Furthermore, treatment response, adverse events, and survivals were evaluated. Results: After 2 treatment cycles, no (0%) patients achieved complete response (CR), 7 (5.0%) patients achieved partial response (PR), 112 (80.0%) patients achieved standard deviation (SD), and 21 (15.0%) patients achieved progressive disease (PD), resulting in objective response rate (ORR) of 5.0% and disease control rate (DCR) of 85.0%. After 4 treatment cycles, no (0%) patients achieved CR, 3 (4.3%) patients achieved PR, 51 (74.0%) patients achieved SD, and 15 (21.7%) patients achieved PD, resulting in ORR of 4.3% and DCR of 78.3%. For survivals, the median progression-free (PFS) was 3.7 months (95% confidence interval [CI]: 2.7-4.7 months), and the median overall survival (OS) was 12.4 months (95% CI: 9.4-15.3 months). Subsequently, multivariate Cox's regression analyses illuminate that histological type (adenosquamous carcinoma vs. adenocarcinoma) and other mutation apart from epidermal growth factor receptor independently predicted shorter PFS; meanwhile, history of smoke and brain metastases independently predicted decreased OS. Regarding safety, most of the adverse events were at mild grade. Conclusion: Anlotinib displays good efficacy and well-tolerant safety profiles in the treatment of advanced NSCLC patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Quinolines , ErbB Receptors/genetics , Humans , Indoles , Lung Neoplasms/drug therapy , Prognosis , Quinolines/adverse effects , Retrospective Studies , SmokeABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies. It is not easy to be diagnosed in the early stage and is prone to relapse, with a very poor prognosis. And immune cell infiltration and tumor microenvironment play important roles in predicting therapeutic response and prognosis of HCC. Machado-Joseph domain-containing proteases (MJDs), as a gene family extensively involved in tumor progression, has pro-cancer and anti-cancer effects. However, the relationship between MJDs family members and immune cell infiltration and tumor microenvironment in HCC remains unclear. Therefore, cBio Cancer Genomics Portal (cBioPortal), The Cancer Genome Atlas (TCGA), UALCAN, Human Protein Atlas (HPA), MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were performed to investigate the mRNA expression, DNA methylation, clinicopathologic features, immune cell infiltration and other related functions of MJDs family members in HCC. The results indicated that the expression of ATXN3, JOSD1, and JOSD2 was dramatically increased in HCC tissues and cell lines, and was correlated with histological grade, specimen type, TP53 mutation, lymph node metastatic, gender, and age of patients with HCC. Meanwhile, these genes also showed clinical value in improving the overall survival (OS), disease-specific survival (DSS), progression free survival (PFS), and relapse-free survival (RFS) in patients with HCC. The prognostic model indicated that the worse survival was associated with overall high expression of MJDs members. Next, the results suggested that promotor methylation levels of the MJDs family were closely related to these family mRNA expression levels, clinicopathologic features, and prognostic values in HCC. Moreover, the MJDs family were significantly correlated with CD4+ T cells, CD8+ T cells, B cells, neutrophils, macrophages, and DCs. And MJDs family members' expression were substantially associated with the levels of several lymphocytes, immunomoinhibitors, immunomostimulators, chemokine ligands, and chemokine receptors. In addition, the expression levels of MJDs family were significantly correlated with cancer-related signaling pathways. Taken together, our results indicated that the aberrant expression of MJDs family in HCC played a critical role in clinical feature, prognosis, tumor microenvironment, immune-related molecules, mutation, gene copy number, and promoter methylation level. And MJDs family may be effective immunotherapeutic targets for patients with HCC and have the potential to be prognostic biomarkers.
ABSTRACT
Antimony sulfide-selenide (Sb2(S,Se)3) is a promising light-harvesting material for stable and high-efficiency thin-film photovoltaics (PV) because of its excellent light-harvesting capability, abundant elemental storage, and excellent stability. This study aimed to expand the application of Sb2(S,Se)3 solar cells with a substrate structure as a flexible or tandem device. The use of a hydrothermal method accompanied by a postselenization process for the deposition of Sb2(S,Se)3 film based on the solar cell substrate structure was first demonstrated. The mechanism of postselenization treatment on crystal growth promotion of the Sb2(S,Se)3 film and the defect passivation of the Sb2(S,Se)3 solar cell were revealed through different characterization methods. The crystallinity and the carrier transport property of the Sb2(S,Se)3 film improved, and both the interface defect density of the Sb2(S,Se)3/CdS interface and the bulk defect density of the Sb2(S,Se)3 absorber decreased. Through these above-mentioned processes, the transport and collection of electronics can be improved, and the defect recombination loss can be reduced. By using postselenization treatment to optimize the absorber layer, Sb2(S,Se)3 solar cells with the configuration SLG/Mo/Sb2(S,Se)3/CdS/ITO/Ag achieved an efficiency of 4.05%. This work can provide valuable information for the further development and improvement of Sb2(S,Se)3 solar cells.
ABSTRACT
In this work, metal halide perovskite quantum dots (QDs) with Formamidinium (FA) and Cs mixed cations were fabricated using a solution-processed method at room temperature. By controlling Cs doping ratios in a precursor, the optical properties of mixed-cation perovskite QDs were systematically studied. With the increase in Cs ion doping, the photoluminescence (PL) spectra of perovskite QDs were blueshifted, which was mainly due to the smaller radius of Cs ions than those of FA. Temperature-dependent PL spectra were conducted on mixed-cation perovskite QDs. As the temperature gradually increased from 4 K to 300 K, PL peaks were blue shifted, and full-width at half maximum (FWHM) was widened, which was directly related to lattice thermal expansion and the carrier-photon coupling effect under temperature variation. At the same time, excess Cs ion doping had a prominent influence on optical properties at low temperatures, which was mainly due to the introduction of detrimental defects in perovskite crystals. Therefore, it is particularly important to control doping concentration in the preparation of high-quality perovskite QDs and efficient photoelectric devices.
ABSTRACT
Single-photon emitters (SPEs) in hexagonal boron nitride (hBN) are promising candidates for quantum light generation. Despite this, techniques to control the formation of hBN SPEs down to the monolayer limit are yet to be demonstrated. Recent experimental and theoretical investigations have suggested that the visible wavelength single-photon emitters in hBN originate from carbon-related defects. Here, we demonstrate a simple strategy for controlling SPE creation during the chemical vapor deposition growth of monolayer hBN via regulating surface carbon concentration. By increasing the surface carbon concentration during hBN growth, we observe increases in carbon doping levels by 2.4-fold for B-C bonds and 1.6-fold for N-C bonds. For the same samples, we observe an increase in the SPE density from 0.13 to 0.30 emitters/µm2. Our simple method enables the reliable creation of hBN SPEs in monolayer samples for the first time, opening the door to advanced two-dimensional (2D) quantum state engineering.
ABSTRACT
Laser ablation of semiconductor silicon has been extensively studied in the past few decades. In the ultrashort pulse domain, whether in the fs scale or ps scale, the pulse energy fluence threshold in the ablation of silicon is strongly dependent on the pulse width. However, in the ns pulse scale, the energy fluence threshold dependence on the pulse width is not well understood. This study elucidates the interaction energy dependency on pulse width in ns NIR laser ablation of silicon. The level of ablation or melting was determined by the pulse energy deposition rate, which was proportional to laser peak power. Shorter pulse widths with high peak power were likely to induce surface ablation, while longer pulse widths were likely to induce surface melting. The ablation threshold increased from 5.63 to 24.84 J/cm2 as the pulse width increased from 26 to 500 ns. The melting threshold increased from 3.33 to 5.76 J/cm2 as the pulse width increased from 26 to 200 ns, and then remained constant until 500 ns, the longest width investigated. Distinct from a shorter pulse width, a longer pulse width did not require a higher power level for inducing surface melting, as surface melting can be induced at a lower power with the longer heating time of a longer pulse width. The line width from surface melting was less than the focused spot size; the line appeared either as a continuous line at slow scanning speed or as isolated dots at high scanning speed. In contrast, the line width from ablation significantly exceeded the focused spot size.
ABSTRACT
Long noncoding RNA LAMTOR5 antisense RNA 1 (LAMTOR5-AS1) has been certified as a risk predictor and diagnostic biomarker of prostate cancer. However, the expression and exact roles of LAMTOR5-AS1 in non-small cell lung cancer (NSCLC) remain unclear. Thus, we measured LAMTOR5-AS1 expression in NSCLC and gauged its clinical value. The detailed roles and downstream working mechanism of LAMTOR5-AS1 in NSCLC were comprehensively unraveled. qRT-PCR was applied to measure gene expression. Functionally, utilizing small interfering RNA, LAMTOR5-AS1 was ablated, and the functional alterations were addressed by means of different experiments. The targeting activities between LAMTOR5-AS1 and microRNA-506-3p (miR-506-3p) and between miR-506-3p and E2F transcription factor 6 (E2F6) were confirmed by RNA immunoprecipitation and luciferase reporter assays. LAMTOR5-AS1 overexpression in NSCLC was verified in TCGA datasets and our own cohort and manifested an evident relationship with poor prognosis. Interference with LAMTOR5-AS1 led to repression of the proliferation, cloning, and metastasis abilities of NSCLC cells in vitro. We further confirmed an obvious increase in LAMTOR5-AS1-silenced NSCLC cell apoptosis. Furthermore, the absence of LAMTOR5-AS1 restricted tumor growth in vivo. Mechanistically, LAMTOR5-AS1 sponged miR-506-3p in NSCLC cells. Furthermore, E2F6, a downstream target of miR-506-3p, was under the control of LAMTOR5-AS1, which was realized by decoying miR-506-3p. Rescue experiments showed that miR-506-3p suppression or E2F6 reintroduction was capable of remitting LAMTOR5-AS1 deficiency-triggered anticarcinogenic actions in NSCLC. Our study confirmed the exact roles of LAMTOR5-AS1 for the first time and revealed that LAMTOR5-AS1 knockdown disrupts the malignancy of NSCLC by targeting the miR-506-3p/E2F6 axis. Targeting the LAMTOR5-AS1/miR-506-3p/E2F6 pathway may be instrumental for managing patients with NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Proliferation , E2F6 Transcription Factor , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Male , MicroRNAs/genetics , RNA, Long Noncoding/geneticsABSTRACT
BACKGROUND: Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. OBJECTIVES: The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. METHODS: We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. CONCLUSIONS: It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.
Subject(s)
Cosmetic Techniques , Dermal Fillers , Embolism , Arteries , Cosmetic Techniques/adverse effects , Embolism/drug therapy , Embolism/etiology , Humans , Hyaluronic Acid , Hyaluronoglucosaminidase , Injections, Intra-Arterial , NecrosisABSTRACT
Sb2Se3, one of the most desirable absorption materials for next-generation thin-film solar cells, has an excellent photovoltaic characteristic. The [hk1]-oriented (quasi-vertically oriented) Sb2Se3 thin film is more beneficial for promoting efficient carrier transport than the [hk0]-oriented Sb2Se3 thin film. Controlling thin-film orientation remains the main obstacle to the further improvement in the efficiency of Sb2Se3-based solar cells. In this work, the controlled [hk0] or [hk1] orientation of the Sb2Se3 precursor is readily adjusted by tuning the substrate temperature and the distance between the source and the sample in close-space sublimation (CSS). Well-crystallized stoichiometric Sb2Se3 thin films with the desired orientation and large crystal grains are successfully prepared after selenization. Sb2Se3 thin-film solar cells in a substrate configuration of glass/Mo/Sb2Se3/CdS/ITO/Ag are fabricated with a power conversion efficiency of 4.86% with a record open-circuit voltage (VOC) of 509 mV. The significant improvement in VOC is closely related to the quasi-vertically oriented Sb2Se3 absorber layer with reduced deep-level defect density in the bulk and defect passivation at the Sb2Se3/CdS heterojunction. This work indicates that CSS and selenization show a remarkable potential for the fabrication of high-efficiency Sb2Se3 solar cells.