Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study.

Oseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van't Hoff equation were - 77.49 kJ/mol, -176.54 J/(mol∙K), and - 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.

Selective Activation of G Protein-Coupled Estrogen Receptor 1 (GPER1) Reduces ER Stress and Pyroptosis via AMPK Signaling Pathway in Experimental Subarachnoid Hemorrhage.

Neuroinflammation is a critical pathogenic event following hemorrhagic stroke. Endoplasmic reticulum (ER) stress-induced apoptosis and nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3)-associated pyroptosis can contribute to the escalation of neuroinflammatory responses, leading to increased brain damage. G protein-coupled estrogen receptor 1(GPER1), as the most extensively characterized brain-derived estrogen, was reported to trigger neuroprotective effects. However, the anti-apoptotic and anti-pyroptotic effect of GPER1 activation and the underlying mechanism has not been fully elucidated. We established the experimental SAH model by intravascular perforation. The GPER1 selective agonist G1 was intravenously administered 1 h following SAH. For mechanistic exploration, the selective inhibitor of adenosine monophosphate-activated protein kinase (AMPK), dorsomorphin, was administered via intracerebroventricular injection 30 min prior to SAH induction. Post-SAH assessments included SAH grade, the short-term and long-term neurological outcomes, brain edema, cerebral blood flow, transmission electron microscopy (TEM), western blot (WB), ELISA, TUNEL staining, Fluoro-Jade C staining (FJC), and immunofluorescence staining. The expression of GPER1 was observed to elevate at 6 h and peaked at 24 h subsequent to SAH, predominantly co-localized with neurons. Post-treatment with G1 markedly ameliorated both the short-term and long-term neurological deficits of SAH mouse, as well as inhibiting the expression of neuronal ER stress-associated apoptotic proteins (i.e., CHOP, GRP78, Caspase-12, Cleaved Caspase-3, Bax, Bcl2) and pyroptosis-associated proteins (i.e., NLRP3, ASC, Cleaved Caspase-1). Additionally, our research revealed that inhibition of AMPK with dorsomorphin attenuated the neuroprotective effects of G1. This was accompanied by modifications in the molecular pathways associated with ER stress-induced apoptosis and pyroptosis. These data herein elucidated that GPER1 exerted neuroprotective effects by mitigating neuroinflammation in an AMPK-dependent manner, which modulates neuronal ER stress-associated apoptosis and pyroptosis. Boosting the anti-apoptotic and anti-pyroptotic effect by activating GPER1 may be an efficient treatment strategy for SAH patients.

Ultrasound combined with urokinase under key-shaped bone window enhances blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage.

OBJECTIVE: Minimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage. METHODS: The blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group. RESULTS: A total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342). CONCLUSIONS: Our study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results.

Spontaneous brain activity in the hippocampal regions could characterize cognitive impairment in patients with Parkinson's disease.

OBJECTIVE: This study aimed to investigate whether spontaneous brain activity can be used as a prospective indicator to identify cognitive impairment in patients with Parkinson's disease (PD). METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) was performed on PD patients. The cognitive level of patients was assessed by the Montreal Cognitive Assessment (MoCA) scale. The fractional amplitude of low-frequency fluctuation (fALFF) was applied to measure the strength of spontaneous brain activity. Correlation analysis and between-group comparisons of fMRI data were conducted using Rest 1.8. By overlaying cognitively characterized brain regions and defining regions of interest (ROIs) based on their spatial distribution for subsequent cognitive stratification studies. RESULTS: A total of 58 PD patients were enrolled in this study. They were divided into three groups: normal cognition (NC) group (27 patients, average MoCA was 27.96), mild cognitive impairment (MCI) group (21 patients, average MoCA was 23.52), and severe cognitive impairment (SCI) group (10 patients, average MoCA was 17.3). It is noteworthy to mention that those within the SCI group exhibited the most advanced chronological age, with an average of 74.4 years, whereas the MCI group displayed a higher prevalence of male participants at 85.7%. It was found hippocampal regions were a stable representative brain region of cognition according to the correlation analysis between the fALFF of the whole brain and cognition, and the comparison of fALFF between different cognitive groups. The parahippocampal gyrus was the only region with statistically significant differences in fALFF among the three cognitive groups, and it was also the only brain region to identify MCI from NC, with an AUC of 0.673. The paracentral lobule, postcentral gyrus was the region that identified SCI from NC, with an AUC of 0.941. The midbrain, hippocampus, and parahippocampa gyrus was the region that identified SCI from MCI, with an AUC of 0.926. CONCLUSION: The parahippocampal gyrus was the potential brain region for recognizing cognitive impairment in PD, specifically for identifying MCI. Thus, the fALFF of parahippocampal gyrus is expected to contribute to future study as a multimodal fingerprint for early warning.

Surgical treatment of traumatic frontal hematoma: comparison of the endoscopic supraorbital approach with frontotemporal approach.

Background: The objective of this study was to compare the efficacy, safety, and outcomes of the endoscopic supraorbital approach and frontotemporal approach for the treatment of traumatic frontal hematoma, with the aim of demonstrating the feasibility of the endoscopic supraorbital approach. Methods: A total of 24 cases underwent hematoma evacuation, including 10 cases using the endoscopic supraorbital approach and 14 cases using the frontotemporal approach. Baseline demographic data, hematoma clearance rate, blood loss, postoperative complications, and 6-month outcomes were retrospectively analyzed. Results: Both approaches effectively evacuated the hematoma, with hematoma clearance rates of 90.97 ± 10.23% in the endoscopic supraorbital group and 85.29 ± 16.15% in the frontotemporal approach group (p > 0.05). The supraorbital approach group demonstrated significantly shorter operation times compared to the frontotemporal approach group (116.50 ± 28.19 min vs. 193.29 ± 72.55 min, p < 0.05), as well as significantly less blood loss (55.00 ± 33.08 mL vs. 685.71 ± 840.20 mL, p < 0.05). There was no significant difference in the rate of postoperative complications between the two groups, and the majority of patients achieved favorable outcomes with a Glasgow Outcome Scale score of 4 or 5 in both groups. Conclusion: Compared to the frontotemporal approach, the endoscopic supraorbital approach offers advantages such as shorter operation times, reduced blood loss, similar treatment effects, and comparable complication rates. Therefore, the endoscopic supraorbital approach may serve as a viable alternative for the treatment of traumatic frontal hematoma.

Effect of Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation on Liver Function and Immune Function in Patients with Hepatocellular Carcinoma.

Objectives: To investigate the effects of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) on liver function and immune function in patients with hepatocellular carcinoma (HCC). Methods: From December 2016 to January 2019, patients with primary liver cancer who could not be operated on were selected as the study subjects. 170 patients were randomly divided into two groups. The control group was treated with transcatheter arterial chemoembolization (n = 85). The patients in the observation group were treated with transcatheter arterial chemoembolization combined with radiofrequency ablation (n = 85). The clinical effects of the two groups were analyzed. The changes of liver function and immune function were detected by automatic biochemical analyzer before and after treatment. The changes of hypoxia inducible factor-1 (HIF1) alpha and vascular endothelial growth factor (VEGF) levels before and after treatment were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: The total effective rate in the observation group was significantly higher than that in the control group (P < 0.05). After treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), CD8+, HIF1 alpha, and VEGF decreased significantly (P < 0.05), while levels of total bilirubin, direct bilirubin, indirect bilirubin, CD3+, CD4+, and CD4+/CD8+ increased significantly (P < 0.05). The changes of the above indexes in the observation group were more significant than those in the control group (P < 0.05). Conclusion: Hepatic arterial chemoembolization combined with radiofrequency ablation has a significant effect on liver function and immune function in patients with liver cancer, which may be related to the abnormal levels of HIF1α and vascular endothelial growth factor.

Organic Cation Diffusion-Induced Heterogeneous Viscoelasticity in Organic-Inorganic Hybrid Perovskite Polycrystalline Films.

Organic-inorganic hybrid perovskite (OIHP) polycrystalline films are the key light-absorbing layers of laminated-structure OIHP-based devices that have attracted increasing attention in photoelectronics and flexible electronics. Internal stresses induced by the mismatched responses of laminated layers to long-term and cyclic multiphysical fields generate time-dependent mechanical deformation in OIHP polycrystalline films, which makes the mechanical constitution relation of great significance. However, few studies focus on either the mechanical properties and behaviors of OIHP polycrystalline films or the underlying mechanism coupled with the grain structure and ion diffusion. Here, we uncovered the heterogeneous viscoelasticity of MAPbBr3 films strongly correlated with the grain structure. Combining experiments and modeling, we revealed that the organic cation diffusion from grain interiors to grain boundaries leads to heterogeneity in the chemical distribution and viscoelastic modulus. Our work provides the nanomechanical understanding of the OIHP polycrystalline films that are crucial for safety design and performance optimization in OIHP-based electronics.

Early assessment of the efficacy of noninvasive ventilation tested by HACOR score to avoid delayed intubation in patients with moderate to severe ARDS.

BACKGROUND: Use of noninvasive ventilation (NIV) in patients with moderate to severe ARDS is controversial. We aimed to use HACOR (combination of heart rate, acidosis, consciousness, oxygenation and respiratory rate) score to comprehensively assess the efficacy of NIV in ARDS patients with PaO2/FiO2 ⩽ 150 mmHg. METHODS: Secondary analysis was performed using the data collected from two databases. We screened the ARDS patients who used NIV as a first-line therapy. Patients with PaO2/FiO2 ⩽ 150 mmHg were enrolled. NIV failure was defined as requirement of intubation. RESULTS: A total of 224 moderate to severe ARDS patients who used NIV as a first-line therapy were enrolled. Of them, 125 patients (56%) experienced NIV failure and received intubation. Among the intubated patients, the survivor had shorter time from initiation of NIV to intubation than nonsurvivors (median 10 vs 22 h, p < 0.01). The median differences of HACOR score before and 1-2 h of NIV were 1 point (interquartile range: 0-3). We defined the patients with △HACOR >1 as responders (n = 102) and the rest to non-responders (n = 122). Compared to non-responders, the responders had higher HACOR score before NIV. However, the HACOR score was lower in the responders than non-responders after 1-2 h, 12 h, and 24 h of NIV. The responders also had lower NIV failure rate (36% vs 72%, p < 0.01) and lower 28-day mortality (32% vs 47%, p = 0.04) than non-responders. CONCLUSIONS: NIV failure was high among patients with moderate to severe ARDS. Delayed intubation is associated with increased mortality. The reduction of HACOR score after 1-2 h of NIV can identify the patients who respond well to NIV.

Prognostic value of hypothyroidism in patients undergoing intensity-modulated radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. METHODS: The clinical data of 284 NPC patients, who received intensity-modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. RESULTS: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease-free survival (DFS) (p = 0.002) and relapse-free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). CONCLUSIONS: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required.

LINC00641 contributes to nasopharyngeal carcinoma cell malignancy through FOXD1 upregulation at the post-transcriptional level.

Nasopharyngeal carcinoma (NPC) is a common tumor in the head and neck and is prevalent in China, especially in the southern regions. Molecular mechanisms have attracted much attention in NPC research. FOXD1 has been reported to be a tumor promoter in various cancers. The present study was designed to explore the function of FOXD1 in NPC cells. Functional analyses, including the trypan blue staining assay, EdU and JC-1 assay, and flow cytometry analysis, revealed that FOXD1 facilitated NPC cell proliferation and inhibited NPC cell apoptosis. Next, by means of "starBase" database and mechanism analyses, such as RIP assay, RNA pull-down assay and luciferase reporter assay, miR-378a-3p was found to target FOXD1 and negatively regulate FOXD1 expression in NPC cells. Moreover, miR-378a-3p plays a suppressive role in NPC cells. LINC00641 was identified as a sponge of miR-378a-3p and positively modulated FOXD1 expression in NPC cells. Finally, a series of rescue assays indicated that LINC00641 accelerated NPC cell proliferation and hindered NPC cell apoptosis through FOXD1 upregulation. In conclusion, the present study demonstrated an innovative ceRNA mechanism of LINC00641/miR-378a-3p/FOXD1 in NPC cells, which might provide new insights into NPC treatment.

Donor-Acceptor Competition via Halide Vacancy Filling for Oxygen Detection of High Sensitivity and Stability by All-Inorganic Perovskite Films.

Oxygen detection by organic-inorganic halide perovskites (OIHPs) has demonstrated advantages in operating temperature, response time, and reversibility over traditional materials. However, OIHPs can only sense O2 in light and the unavoidable O2 exposure during detection easily induces the degradation of OIHPs. The trade-off between sensitivity and stability makes the OIHP-based oxygen sensors impractical. By replacing organic groups with Cs, the compact films of all-inorganic halide perovskites (AIHPs) that can adsorb O2 at grain boundaries in dark are developed. AIHPs show conductance increase of 1875.5% from 1 × 10-5 to 700 Torr of O2 pressure, associated with full reversibility and long-term stability. Combining experiments and modeling, this work reveals the donor-acceptor competition via halide vacancy filling leading to the modulation of carrier concentration and mobility. This work offers understandings on oxygen sensing by perovskite materials and paves the way for further optimization of AIHPs as promising oxygen sensors with high sensitivity and stability.

Defects Engineering of Lightweight Metal-Organic Frameworks-Based Electrocatalytic Membrane for High-Loading Lithium-Sulfur Batteries.

The sluggish kinetics and shuttle effect of lithium polysulfide intermediates are the major issues that retard the practical applications of lithium-sulfur (Li-S) batteries. Herein, we introduce a defect engineering strategy to construct a defected-UiO-66-NH2-4/graphene electrocatalytic membrane (D-UiO-66-NH2-4/G EM) which could accelerate the conversion of lithium polysulfides in high sulfur loadings and low electrolyte/sulfur (E/S) ratio Li-S batteries. Metal-organic frameworks (UiO-66-NH2) can be directionally chemical engraved to form concave octahedra with abundant defects. According to electrocatalytic kinetics and DFT calculations studies, the D-UiO-66-NH2-4 architecture effectively provides ample sites to capture polysulfides via strong chemical affinity and effectively delivers electrocatalytic activity of polysulfide conversion. As a result, a Li-S battery with such an electrocatalytic membrane delivers a high capacity of 12.3 mAh cm-2 (1013 mAh g-1) at a sulfur loading up to 12.2 mg·S cm-2 under a lean electrolyte condition (E/S = 5 µL mg-1-sulfur) at 2.1 mA cm-2 (0.1 C). Moreover, a prototype soft package battery also exhibits excellent cycling stability with a maintained capacity of 996 mAh g-1 upon 100 cycles.

Recent Progress on Vanadium Dioxide Nanostructures and Devices: Fabrication, Properties, Applications and Perspectives.

Vanadium dioxide (VO2) is a typical metal-insulator transition (MIT) material, which changes from room-temperature monoclinic insulating phase to high-temperature rutile metallic phase. The phase transition of VO2 is accompanied by sudden changes in conductance and optical transmittance. Due to the excellent phase transition characteristics of VO2, it has been widely studied in the applications of electric and optical devices, smart windows, sensors, actuators, etc. In this review, we provide a summary about several phases of VO2 and their corresponding structural features, the typical fabrication methods of VO2 nanostructures (e.g., thin film and low-dimensional structures (LDSs)) and the properties and related applications of VO2. In addition, the challenges and opportunities for VO2 in future studies and applications are also discussed.

Nonvolatile ferroelectric field effect transistor based on a vanadium dioxide nanowire with large on- and off-field resistance switching.

We fabricate a ferroelectric field effect transistor (FeFET) based on a semiconducting vanadium dioxide (VO2) nanowire (NW), and we investigate its electron transport characteristics modulated by the ferroelectric effects. The transistor consists of a single VO2 NW as the channel and a ferroelectric Pb(Zr0.52Ti0.48)O3 (PZT) thin film as the dielectric gate. The conductance of the VO2 NW channel is found to be feasibly modulated by the ferroelectric gate with an 85% resistance change under the gate voltage of 18 V (at an applied field of about 0.75 MV cm-1). The electron transport property of the device can be controlled by the remnant polarization of the PZT layer due to the nonvolatile property of the ferroelectric gate, with an off-field change of channel resistance up to 50%. Moreover, multiple resistive states can be achieved by sweeping gate voltage across the device appropriately. These results demonstrate that ferroelectric gate modulation is an efficient tool to regulate the electron transport properties of the VO2 NW, and the VO2-NW-FeFET has potential applications in nonvolatile and low-power consumption devices.

Clinical outcomes of patients with nasopharyngeal carcinoma treated with antibiotics for radiation-induced mucositis: a retrospective study.

OBJECTIVE: To examine the effects of antibiotic administration on radiation-induced oral and oropharyngeal mucositis, and on the prognosis of patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively analyzed data for patients with NPC with grade 1/2 or 3/4 mucositis. Forty-two patients with grade 3/4 mucositis received antibiotics. Univariate survival analysis was assessed by Kaplan-Meier survival curves, survival curves were compared using log-rank tests, and multivariate analysis was carried out by Cox regression. RESULTS: A total of 463 patients with NPC were included in the study (194 grade 1/2 mucositis, 269 grade 3/4 mucositis). Univariate analyses identified T-stage, N-stage, clinical stage, type of treatment, and antibiotic use as factors affecting overall and disease-free survival. Multivariate analysis also determined that T-stage, N-stage stage, type of treatment, and antibiotic usage were independent factors affecting overall and disease-free survival. Mucositis improved in 32 of the 42 patients who received antibiotics (76.19%). However, red blood cell count and hemoglobin levels decreased in all patients after antibiotic treatment. CONCLUSIONS: Antibiotics may be effective for the treatment of severe radiation-induced mucositis (grade 3/4) during chemoradiotherapy, but may potentially adversely affect the prognosis of patients with NPC.

Binding interaction of sodium benzoate food additive with bovine serum albumin: multi-spectroscopy and molecular docking studies.

Sodium benzoate (SB) is widely used as a preservative in food industry, and bovine serum albumin (BSA) is a major carrier protein similar to human serum albumin (HSA), the study of the binding between the two has great significance on human health. In this paper, we systematically investigated the binding of SB and BSA under the simulated physiological conditions combining with various common analytical methods, e.g., fluorescence, UV-vis absorption, synchronous fluorescence and circular dichroism (CD) spectra, as well as molecular docking method. The fluorescence quenching measurements were respectively carried out at 298 K, 303 K and 308 K using the Stern-Volmer method. The results reveal that ground state SB-BSA complex was formed within the binding constants from 2.02 × 104 to 7.9 × 103 M-1. Meanwhile, the negative values of ΔH 0 (- 43.92 kJ mol-1) and ΔS 0 (- 111.6 J mol-1 K-1) demonstrated that both the hydrogen binding interaction and van der Waals forces contributed to stabilizing the SB-BSA complex. The site marker competitive experiments show that the SB and BSA bound at site I. Furthermore, the experimental results of UV-vis absorption, synchronous fluorescence and CD spectra indicate that the binding of SB and BSA may change the conformation of BSA. In addition, the molecular docking experiment suggests that hydrogen bond was formed in the interaction between SB and BSA.

A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC).

BACKGROUND: This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients. METHODS: The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated. RESULTS: A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = - 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode. CONCLUSION: NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

High Current Density and Low Hysteresis Effect of Planar Perovskite Solar Cells via PCBM-doping and Interfacial Improvement.

We propose a doping method by using [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) to fill the grain boundary interstices of the methylammonium lead iodide (CH3NH3PbI3) perovskite for the elimination of pinholes. A sandwiched PCBM layer is also used between the perovskite and TiO2 layers to improve the interfacial contact. By using these two methods, the fabricated perovskite solar cells show a low hysteresis effect and high current density, which result from the improved compactness at the grain boundaries of the perovskite surface and the interface between the TiO2/perovskite layers. The theoretical and experimental results indicate that PCBM can effectively suppress carrier recombination, regardless of the interfacial layer or dopant. We also found that the dark current reduced during the analysis of dark state current-voltage ( I- V) characteristics. The slopes of the I- V curves for the fluorine-doped tin oxide/PCBM-doped perovskite/Au device reduce monotonically with the increase in the PCBM concentration from 0.01 to 0.1 wt %, which suggest the decreasing defects in the perovskite layer. By tuning the PCBM doping and controlling the preparation process, we have successfully fabricated a planar TiO2/PCBM-based PCBM-doped perovskite photovoltaic device that reaches a high current density of 22.6 mA/cm2 and an outstanding photoelectric conversion efficiency up to 18.3%. The controllability of the PCBM doping concentration and interfacial preparation shed light on further optimization of the photoelectric conversion efficiency of perovskite solar cells.

Stable knockdown of ZBTB7A promotes cell proliferation and progression in nasopharyngeal carcinoma.

AIMS: Although high expression of ZBTB7A is positively relative to metastasis in nasopharyngeal carcinoma (NPC) patients, the association between its low expression and metastasis of NPC remains unclear. The present study aimed to definitely identify the association. METHODS: The level of ZBTB7A was effectively knocked down by stable transfection of short hair RNA plasmid in NPC cell lines CNE2 and 5-8F (shRNA-CNE2 and shRNA-5-8F), compared with the cells that stably transfected empty plasmid (NC-CNE2 and NC-5-8F). The levels of ZBTB7A were assessed by real-time polymerase chain reaction and Western blot in the cell lines. MTT assay, colorimetric focus-formation assay, flow cytometry, wound healing assay, transwell assays, and xenograft model were performed to analyze cell vitality, proliferation, cell cycle, migration, invasion, and tumorigenicity. RESULTS: The levels of ZBTB7A were effectively reduced in shRNA-CNE2 and shRNA-5-8F. Their carcinogenicity was stronger separately than the abilities of NC-CNE2 and NC-5-8F. NC-CNE2 and shRNA-CNE2 were selected to establish the xenograft model because of their stronger tumorigenicity than NC-6-10B and shRNA-5-8F. The assay showed that shRNA-CNE2 had stronger tumorigenicity than NC-CNE2. CONCLUSIONS: The results demonstrated the reverse association between the expression of ZBTB7A and the tumorigenicity of NPC. We postulate that some oncogenic pathways, which are suppressed by ZBTB7A, will vicariously promote the proliferation and progression of NPC when ZBTB7A is decreased.

Up-regulation of the IRX2 gene predicts poor prognosis in nasopharyngeal carcinoma.

Aberrant expression of the IRX2 gene contributes to the oncogenesis and progression of various cancers. In this study, we analyzed the clinical significance and the prognostic value of mRNA expression level of the IRX2 gene in nasopharyngeal carcinoma (NPC) patients, with the goal to find a novel prognostic biomarker for NPC. Tissue samples were collected prior to treatment from 71 NPC patients for the detection of mRNA expression level of a total of 31503 genes, with high throughput screening of the mRNA expression profile. The Kaplan-Meier curves and log-rank test were used for univariate analyses to determine if the mRNA expression level of IRX2 and other 31502 genes, as well as clinical characteristics were of prognostic value for overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). Regularized Cox regression was performed to test the contribution of prognostic factors to OS, DMFS, and DFS of NPC patients. The Cox proportional hazard model was used to test the independence of prognostic effect of IRX2 and other clinical features. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the predictive power of IRX2 gene. Univariate analyses showed a higher mRNA expression level of the IRX2 gene correlated with shorter OS (P = 0.001), DMFS (P = 0.003), and DFS (P = 0.007). Regularized Cox regression and Cox proportional hazard model analyses further showed that ahigher mRNA expression level of the IRX2 gene in the primary NPC was an independent prognostic factor for OS (Coxnet beta = 0.03, Cox proportion hazard model P = 0.038), DMFS (Coxnet beta = 0.018, Cox proportion hazard model P = 0.01) and DFS (Coxnet beta = 0.008, Cox proportion hazard model P = 0.029). The AUC showed that the mRNA expression level of the IRX2 gene is a significant predictor for predicting the OS (AUC value = 0.7105) and DMFS (AUC value = 0.7027) of NPC patients. Our results demonstrated that the IRX2 gene may be a novel independent unfavorable prognostic factor for NPC patients.