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This article reviews the anti-penetration principles and strengthening mechanisms of metal materials, ranging from macroscopic failure modes to microscopic structural characteristics, and further summarizes the micro–macro correlation in the anti-penetration process. Finally, it outlines the constitutive models and numerical simulation studies utilized in the field of impact and penetration. From the macro perspective, nine frequent penetration failure modes of metal materials are summarized, with a focus on the analysis of the cratering, compression shear, penetration, and plugging stages of the penetration process. The reasons for the formation of adiabatic shear bands (ASBs) in metal materials with different crystal structures are elaborated, and the formation mechanism of the equiaxed grains in the ASB is explored. Both the strength and the toughness of metal materials are related to the materials’ crystal structures and microstructures. The toughness is mainly influenced by the deformation mechanism, while the strength is explained by the strengthening mechanism. Therefore, the mechanical properties of metal materials depend on their microstructures, which are subject to the manufacturing process and material composition. Regarding numerical simulation, the advantages and disadvantages of different constitutive models and simulation methods are summarized based on the application characteristics of metal materials in high-speed penetration practice. In summary, this article provides a systematic overview of the macroscopic and microscopic characteristics of metal materials, along with their mechanisms and correlation during the anti-penetration and impact-resistance processes, thereby making an important contribution to the scientific understanding of anti-penetration performance and its optimization in metal materials.

Abstract Objective The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. Methods Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. Results A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0–2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947–0.982; p

Abstract To improve the thermal and combustion properties of nanothermites, a design theory of changing the state of matter and structural state of the reactants during reaction was proposed. The Al/MoO3/KClO4 (Kp) nanothermite was prepared and the Al/MoO3 nanothermite was used as a control. SEM and XRD were used to characterize the nanothermites; DSC was used to test thermal properties; and constant volume and open combustion tests were performed to examine their combustion performance. Phase and morphology characterization of the combustion products were performed to reveal the mechanism of the aluminothermic reaction. The results show that the Al/MoO3/Kp nanothermite exhibited excellent thermal properties, with a total heat release of 1976 J·g− 1, increasing by approximately 33% of 1486 J·g− 1 of the Al/MoO3 nanothermite, and activation energy of 269.66 kJ·mol− 1, which demonstrated higher stability than the Al/MoO3 nanothermite (205.64 kJ·mol− 1). During the combustion test, the peak pressure of the Al/MoO3/Kp nanothermite was 0.751 MPa, and the average pressure rise rate was 25.03 MPa·s− 1, much higher than 0.188 MPa and 6.27 MPa·s− 1 of the Al/MoO3 nanothermite. The combustion products of Al/MoO3 nanothermite were Al2O3, MoO, and Mo, indicating insufficient combustion and incomplete reaction, whereas, the combustion products of Al/MoO3/Kp nanothermite were Al2O3, MoO, and KCl, indicating complete reaction. Their “coral-like” morphology was the effect of reactants solidifying after melting during the combustion process. The characterization of reactants and pressure test during combustion reveals the three stages of aluminothermic reaction in thermites. The excellent thermal and combustion performance of Al/MoO3/Kp nanothermite is attributed to the melt and decomposition of Kp into O2 in the third stage. This study provides new ideas and guidance for the design of high-performance nanothermites.

The WNT/β-catenin signaling pathway plays crucial roles in tumorigenesis and relapse, metastasis, drug resistance, and tumor stemness maintenance. In most tumors, the WNT/β-catenin signaling pathway is often aberrantly activated. The therapeutic usefulness of inhibition of WNT/β-catenin signaling has been reported to improve the efficiency of different cancer treatments and this inhibition of signaling has been carried out using different methods including pharmacological agents, short interfering RNA (siRNA), and antibodies. Here, we review the WNT-inhibitory effects of some FDA-approved drugs and natural products in cancer treatment and focus on recent progress of the WNT signaling inhibitors in improving the efficiency of chemotherapy, immunotherapy, gene therapy, and physical therapy. We also classified these FDA-approved drugs and natural products according to their structure and physicochemical properties, and introduced briefly their potential mechanisms of inhibiting the WNT signaling pathway. The review provides a comprehensive understanding of inhibitors of WNT/β-catenin pathway in various cancer therapeutics. This will benefit novel WNT inhibitor development and optimal clinical use of WNT signaling-related drugs in synergistic cancer therapy.

Abstract Alfalfa, an essential forage crop known for its high yield, nutritional value, and strong adaptability, has been widely cultivated worldwide. The yield and quality of alfalfa are frequently jeopardized due to environmental degradation. Lignin, a constituent of the cell wall, enhances plant resistance to abiotic stress, which often causes osmotic stress in plant cells. However, how lignin responds to osmotic stress in leaves remains unclear. This study explored the effects of osmotic stress on lignin accumulation and the contents of intermediate metabolites involved in lignin synthesis in alfalfa leaves. Osmotic stress caused an increase in lignin accumulation and the alteration of core enzyme activities and gene expression in the phenylpropanoid pathway. We identified five hub genes (CSE, CCR, CADa, CADb, and POD) and thirty edge genes (including WRKYs, MYBs, and UBPs) by integrating transcriptome and metabolome analyses. In addition, ABA and ethylene signaling induced by osmotic stress regulated lignin biosynthesis in a contradictory way. These findings contribute to a new theoretical foundation for the breeding of high-quality and resistant alfalfa varieties.

Abstract Glycoside hydrolase family 1 (GH1) β-glucosidases (BGLUs), are encoded by a large number of genes, which participate in the development and stress response of plants, particularly under biotic and abiotic stresses through the activation of phytohormones. However, there are few studies systematically analyzing stress or hormone-responsive BGLU genes in alfalfa. In this study, a total of 179 BGLU genes of the glycoside hydrolase family 1 were identified in the genome of alfalfa, and then were classified into five distinct clusters. Sequence alignments revealed several conserved and unique motifs among these MsBGLU proteins. Many cis-acting elements related to abiotic stresses and phytohormones were identified in the promoter of some MsBGLUs. Moreover, RNA-seq and RT-qPCR analyses showed that these MsBGLU genes exhibited distinct expression patterns in response to different abiotic stress and hormonal treatments. In summary, this study suggests that MsBGLU genes play crucial roles in response to various abiotic stresses and hormonal responses, and provides candidate genes for stress tolerance breeding in alfalfa.

Abstract Background Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). Methods We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. Results Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12–0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18–0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16–0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18–0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. Conclusions Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. Trial registration Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Abstract Torenia fournieri Lind. is an ornamental plant that is popular for its numerous flowers and variety of colors. However, its genomic evolutionary history and the genetic and metabolic bases of flower color formation remain poorly understood. Here, we report the first T. fournieri reference genome, which was resolved to the chromosome scale and was 164.4 Mb in size. Phylogenetic analyses clarified relationships with other plant species, and a comparative genomic analysis indicated that the shared ancestor of T. fournieri and Antirrhinum majus underwent a whole genome duplication event. Joint transcriptomic and metabolomic analyses identified many metabolites related to pelargonidin, peonidin, and naringenin production in rose (TfR)‐colored flowers. Samples with blue (TfB) and deep blue (TfD) colors contained numerous derivatives of petunidin, cyanidin, quercetin, and malvidin; differences in the abundances of these metabolites and expression levels of the associated genes were hypothesized to be responsible for variety‐specific differences in flower color. Furthermore, the genes encoding flavonoid 3‐hydroxylase, anthocyanin synthase, and anthocyanin reductase were differentially expressed between flowers of different colors. Overall, we successfully identified key genes and metabolites involved in T. fournieri flower color formation. The data provided by the chromosome‐scale genome assembly establish a basis for understanding the differentiation of this species and will facilitate future genetic studies and genomic‐assisted breeding.

Abstract Objective This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. Methods Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0–2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90‐day mortality. Results Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02–2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59–3.34; p = 0.44) or 90‐day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38–1.31; p = 0.27). Interpretation Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Background Steroids have pleiotropic neuroprotective actions including the regulation of inflammation and apoptosis which may influence the effects of ischemia on neurons, glial cells, and blood vessels. The effect of low‐dose methylprednisolone in patients with acute ischemic stroke in the endovascular therapy era remains unknown. This trial investigates the efficacy and safety of low‐dose methylprednisolone (2 mg/kg IV for 3 days) as adjunctive therapy for patients with acute ischemic stroke undergoing endovascular therapy within 24 hours from symptom onset. Methods The MARVEL (Methylprednisolone as Adjunctive Therapy for Acute Large Vessel Occlusion: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy) trial is an investigator‐initiated, prospective, randomized, double‐blind, placebo‐controlled multicenter clinical trial. Up to 1672 eligible patients with anterior circulation large‐vessel occlusion stroke presenting within 24 hours from symptom onset are planned to be consecutively randomized to receive methylprednisolone or placebo in a 1:1 ratio across 82 stroke centers in China. Results The primary outcome is the ordinal shift in the modified Rankin scale score at 90 days. Secondary outcomes include 90‐day functional independence (modified Rankin scale score, 0–2). The primary safety end points include mortality rate at 90 days and symptomatic intracerebral hemorrhage within 48 hours of endovascular therapy. Conclusion The MARVEL trial will provide evidence of the efficacy and safety of low‐dose methylprednisolone as adjunctive therapy for patients with anterior circulation large‐vessel occlusion stroke undergoing endovascular therapy.

Abstract Introduction Admission hyperglycemia and high admission blood glucose levels have been associated with poor outcomes in acute ischemic stroke. However, the relationship between admission hyperglycemia and outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) still remain unclear. This study aimed to investigate the association between admission hyperglycemia and clinical outcomes in ABAO following EVT. Methods Patients from the BASILAR registry with admission blood glucose levels treated with EVT were included. We defined admission hyperglycemia as blood glucose levels ≥ 7.8 mmol/L. The primary outcome was favorable outcome [defined as a modified Rankin Scale score (mRS) of 0–3] at 90 days, Secondary outcomes included other functional outcomes (mRS 0–2, mRS 0–1) at 90 days, symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality at 90 days. Results Of 545 eligible patients included, the median age was 65 (IQR, 56–73) years, and median blood glucose level was 7.36 (IQR, 6.10–9.66) mmol/L. Multivariable logistic regression analysis showed that admission hyperglycemia was associated with decreased favorable outcome (mRS 0–3) (adjusted odds ratio = 0.52; 95% CI 0.35–0.79; P = 0.001), and increased mortality (adjusted odds ratio = 2.67; 95% CI 1.82–3.91; P

There is a high demand for an optimal drug delivery system to treat androgenetic alopecia. Topical application of ISX9, which is a neurogenesis inducer, has been found to stimulate hair follicle (HF) regrowth by upregulating the Wnt/β-catenin signaling pathway, an essential pathway involved in initiating HF growth and development. In the present study, a temperature-sensitive, biopolymer-based, biocompatible, and eco-friendly drug-delivery system was synthesized. This system comprised chitosan-grafted poly(glycidyl methacrylate-co-N-isopropyl acrylamide) (Poly(GMA-co-NIPAAm)@CS-PGNCS) as the shell component and PF127 as the core polymer. The hydrophobic nature of the PF127 block copolymer efficiently dissolved the partially water-soluble drug, ISX9, and the thermos-responsive shell polymer effectively released the drug at a definite skin temperature. The optimized spherical nanoparticles demonstrated the lowest critical solution temperature (LCST) at 32 ± 2 °C with a diameter of 100–250 nm, which delivered encapsulated ISX9 with greater precision than topical ISX9. In a series of in vivo experiments, we demonstrated that ISX9-coated TBNPs upregulated the expression of β-catenin, active β-catenin, Wnt target genes, stemness marker genes, proliferating cell nuclear antigen, HF stem cell markers, and HF markers including VEGF, TGF, and IGF-1 more effectively than topical ISX9. These results suggest that TBNPs could be employed as a platform for effective transdermal delivery of various hydrophobic drugs.

Abstract A novel stripline diplexer design using frequency‐dependent couplings (FDC) to achieve multiple transmission zeros is developed in this paper. The transmission zeros generated by FDCs are flexible and controllable; on the basis of the existing cross‐coupled, more transmission zeros are introduced to improve the frequency selection characteristics. Based on this characteristic, the authors synthesized and designed a 2.6‐GHz diplexer, its transmitting channel filter is five orders with three transmission zeros, and the receiving channel filter is four orders with three transmission zeros. The authors fabricated and measured it, in narrowband, the tested results, synthesis responses and simulation results are well matched with each other, which will provide more flexibility in the design of diplexers for wireless communication system.

Abstract To improve the thermal properties of thermite safely and stably, electrostatic spraying was used to prepare the Al/MoO3 thermite. The Al/MoO3 thermites were detected and characterized by scanning electron microscopy (SEM) and X‐ray diffraction (XRD), and thermal decomposition experiments were carried out by differential scanning calorimetry (DSC). The heat release of the Al/MoO3 thermite prepared by the electrostatic spray (1044 J g−1) is significantly higher than that of the thermite prepared by the ultrasonic (692 J g−1), which is due to more uniform dispersion between Al and MoO3. The initial reaction temperature and activation energy (Ea) of the former keep it steady. Electrostatic spray ensures the safety and stability of the Al/MoO3 thermite. This study provides a new idea for safely and stably improving the thermal properties of thermite by enhancing surface homogenization, which is of great significance for practical applications.

Few studies have reported the clinical outcomes of older adult patients with acute anterior circulation large-vessel occlusion (LVO) who underwent mechanical thrombectomy (MT). Therefore, we investigated the safety, functional outcomes, and predictors of MT for anterior circulation LVO in older adults. We enrolled patients with acute anterior circulation LVO from May 2018 to October 2021 in this retrospective study. Patients were divided into older (≥80 years) and young (

Abstract With the growing popularity of portable and wearable smart electronics, the electromagnetic shielding materials with high shielding effectiveness (SE) as well as light weight and excellent mechanical strength are in high. In this work, the PEDOT:PSS‐based free‐standing conducting film with superior conductivity and mechanical strength is prepared through a facile fabrication. The cellulose nanofibers (CNFs) are first introduced to induce an orderly grow and stack of the PEDOT grains. A phosphoric acid immersion process is then employed to remove the insulating CNF and PSS in the film. The obtained free‐standing conducting film shows a record conductivity of 3508 S cm−1 and its elongation at break reaches 3.75%. Encouragingly, the film delivers an excellent electromagnetic interference (EMI) shielding behavior with a SE of 49 dB in the X‐band (8.2–12.4 GHz) at a thickness of 4 µm. The superior conductivity, mechanical strength, and high SE as well as its facile solution processability make this free‐standing conducting film to be an attractive EMI material for portable and wearable smart electronics.

Abstract Organic single crystals (OSCs) offer a unique combination of both individual and collective properties of the employed molecules, but it remains highly challenging to achieve OSCs with both high mobilities and strong fluorescence emissions for their potential applications in multifunctional optoelectronics. Herein, we demonstrate the design and synthesis of two novel triphenylamine‐functionalized thienoacenes‐based organic semiconductors, 4,8‐distriphenylamineethynylbenzo[1,2‐b:4,5‐b′]dithiophene (4,8‐DTEBDT) and 2,6‐distriphenylamineethynylbenzo[1,2‐b:4,5‐b′]dithiophene (2,6‐DTEBDT), with high‐mobility and strong fluorescence emission. The two compounds show the maximum mobilities up to 0.25 and 0.06 cm2 V−1 s−1, the photoluminescence quantum yields (PLQYs) of 51% and 45%, and the small binding energies down to 55.13 and 58.79 meV. The excellent electrical and optical properties ensured the application of 4,8‐DTEBDT and 2,6‐DTEBDT single crystals in ultrasensitive UV phototransistors, achieving high photoresponsivity of 9.60 × 105 and 6.43 × 104 A W−1, and detectivity exceeding 5.68 × 1017 and 2.99 × 1016 Jones.

Abstract Fluoroelastomer has received increasing attention for energetic materials application due to its high fluorine contents. Different contents (0 wt%–30 wt%) of poly(VDF‐ter‐HFP‐ter‐TFE) terpolymer are added into Al/MnO2 nanothermite. The peak exothermic temperature of thermite reaction for Al/MnO2 system is about 554°C with 1070 Jg−1 heat release. After adding terpolymer, it mainly exists in the gap among Al nanoparticles and MnO2 nanorods, and react with Al and MnO2 at the range of 350 to 540°C before the occurrence of the thermite reaction. 10 wt% terpolymer has relatively little effect on the thermite reaction, but for the samples with higher terpolymer content, more nanothermite components react with terpolymer at an early stage. Ignition and combustion performance show terpolymer can reduce ignition current threshold by up to 9.82% and increase combustion duration time at least several times. The potential reasons for the above results are analyzed. This work can shed light on the application of fluoroelastomer in energetic‐materials.

Abstract Upregulation of transmembrane protein 97 (TMEM97) has been associated with progression and poor outcome in multiple human cancers, including breast cancer. Recent studies suggest that TMEM97 may be involved in the activation of the Wnt/β-catenin pathway. However, the molecular mechanism of TMEM97 action on Wnt/β-catenin signaling is completely unclear. In the current study, TMEM97 was identified as an LRP6-interacting protein. TMEM97 could interact with LRP6 intracellular domain and enhance LRP6-mediated Wnt signaling in a CK1δ/ε-dependent manner. The binding of TMEM97 to LRP6 facilitated the recruitment of CK1δ/ε to LRP6 complex, resulting in LRP6 phosphorylation at Ser 1490 and the stabilization of β-catenin. In breast cancer cells, knockout of TMEM97 attenuated the Wnt/β-catenin signaling cascade via regulating LRP6 phosphorylation, leading to a decrease in the expression of Wnt target genes AXIN2, LEF1, and survivin. TMEM97 deficiency also suppressed cell viability, proliferation, colony formation, migration, invasion, and stemness properties in breast cancer cells. Importantly, TMEM97 knockout suppressed tumor growth through downregulating the Wnt/β-catenin signaling pathway in a breast cancer xenograft model. Taken together, our results revealed that TMEM97 is a positive modulator of canonical Wnt signaling. TMEM97-mediated Wnt signaling is implicated in the tumorigenesis of breast cancer, and its targeted inhibition may be a promising therapeutic strategy for breast cancer.

Introduction: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Single-cell sequencing technology can achieve an accurate and unbiased assessment of cell heterogeneity. Therefore, it is necessary to explore the molecular characteristics of GC-related malignant cells at a single-cell resolution. Methods: Single-cell RNA sequencing GC profiles were collected from the Gene Expression Omnibus database. Moreover, feature gene sets of metabolic pathways and hypoxia signals were collected from the Molecular Signatures Database. The marker genes of specific cell types were collected from the published literature and CellMarker database. The R package InferCNV was used to calculate the copy-number variations of cells and to identify real cancer cells. The weighted relative pathway activity algorithm was used to evaluate the differences in metabolic activity between cell types. Results: Our study found that cancer epithelial cells exhibited individual differences in molecular features and showed metabolic heterogeneity. Oxidative phosphorylation and glycolytic pathway activity were the major contributors to the metabolic heterogeneity of cancer epithelial cells. Furthermore, we used the hypoxia signaling pathway to indirectly evaluate the oxygen content of cells and found that hypoxia contributed to the heterogeneity of cancer epithelial cells. Finally, functional identification of genes co-expressed with HIF1A showed that the reprogramming of the oxidative stress response contributed to the tumor malignant progression. Conclusions: This study described hypoxia-induced metabolic reprogramming of GC at a single-cell level, partially addressing the lack of insight into the heterogeneity of cancer cell metabolism when using traditional sequencing technology.

ObjectiveThe aim of this study was to evaluate the effectiveness and safety of rescue therapy, a therapy in which rescue devices such as balloon angioplasty, Apollo stent, Wingspan stent, Solitaire stent, or other self-expanding stents are used after the failure of mechanical thrombectomy (MT) and to determine the most effective rescue measure for acute basilar artery occlusion (BAO) after the failure of MT.MethodsFor this study, we recruited patients from the BASILAR registry. All participants were divided into three groups: the recanalized with rescue therapy group, the recanalized without rescue therapy group, and the non-recanalized group. Clinical outcomes at 90 days and 1 year were compared. The association of rescue measures with favorable outcomes (modified Rankin Scale [mRS] score of 0–3) in patients achieving successful recanalization via rescue therapy was estimated using multivariate logistic regression analyses.ResultsAmong the participants, recanalization failure was found in 112 patients and successful recanalization in 473 patients, with 218 patients receiving rescue therapy and 255 patients without rescue therapy. Of these, 111 (43.5%) patients in the recanalized without rescue therapy group, 65 (29.8%) patients in the recanalized with rescue therapy group, and nine (8.0%) patients in the non-recanalized group achieved favorable outcomes at 90 days. Both the recanalization with rescue therapy and the recanalization without rescue therapy groups were associated with favorable outcomes at 90 days and 1 year compared with the non-recanalized group. Moreover, in patients receiving rescue therapy, Wingspan stents, Apollo stents, and balloon angioplasty were associated with higher rates of favorable outcomes at 90 days and 1 year than Solitaire stents.ConclusionWhether rescue therapy is administered or not, recanalization leads to favorable outcomes in patients with acute BAO. For acute BAO after MT failure, balloon angioplasty, Wingspan stenting, and Apollo stenting could be considered effective and safe rescue options but not Solitaire stenting.

Medicago falcata L. is an important legume forage grass with strong drought resistant, which could be utilized as an important gene pool in molecular breed of forage grass. In this study, M. falcata seedlings were treated with 400 mM mannitol to simulate drought stress, and the morphological and physiological changes were investigated, as well as the transcriptome changes of M. falcata seedlings at different treatment time points (0 h, 2 h, 6 h, 12 h, 24 h, 36 h and 48 h). Transcriptome analyses revealed four modules were closely related with drought response in M. falcata by WGCNA analysis, and four ERF transcription factor genes related with drought stress were identified (MfERF053, MfERF9, MfERF034 and MfRAP2.1). Among them, MfERF053 was highly expressed in roots, and MfERF053 protein showed transcriptional activation activity by transient expression in tobacco leaves. Overexpression of MfERF053 in Arabidopsis improved root growth, number of lateral roots and fresh weight under drought, salt stress and exogenous ABA treatments. Transgenic Arabidopsis over-expressing MfERF053 gene grew significantly better than the wild type under both drought stress and salt stress when grown in soil. Taken together, our strategy with transcriptome combined WGCNA analyses identified key transcription factor genes from M. falcata, and the selected MfERF053 gene was verified to be able to enhance drought and salt resistance when over-expressed in Arabidopsis.

Background and purposeIschemic stroke is related to inflammation. We investigated leukocyte counts, neutrophil counts, and NLR (neutrophil-to-lymphocyte ratio) to explore their prognostic potential and determine if high neutrophil counts before endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO) are associated with worse outcomes at 90 days post-EVT.MethodsLeukocyte and neutrophil counts and NLR were determined in eligible patients from the Acute Basilar Artery Occlusion Study (BASILAR). Patients were divided into four groups according to leukocyte and neutrophil counts and NLR quartiles. The primary outcome was a favorable outcome based on the modified Rankin Scale (mRS: 0–3). The secondary outcome was functional independence (mRS 0–2). The safety outcome was mortality, and an unfavorable outcome was mRS 4–6. Successful reperfusion was mTICI (modified Thrombolysis in Cerebral Infarction) of 2b or 3. All the data were collected within 90 days after EVT.ResultsWe enrolled 586 patients in the study. The leukocyte and neutrophil counts and NLR were significantly associated with clinical outcomes in all patients though no effects were seen in some intervals. Of these three parameters, the neutrophil count had the most significant impact, negatively affecting the outcome. The findings were similar in patients who were successfully recanalized.ConclusionHigher neutrophil counts predicted worse clinical outcomes 90 days after EVT. This finding supports the deleterious role of inflammation in patients with acute BAO despite EVT or successful recanalization.

BackgroundThis study aimed to investigate the clinical outcomes of endovascular treatment (EVT) for distal basilar artery occlusion (BAO) and compare them with the outcomes of standard medical treatment (SMT) in daily clinical practice.MethodsPatients with distal BAO enrolled in the BASILAR study from January 2014 to May 2019 were included. Differences in clinical outcomes were analyzed using Pearson's chi-square test and multivariable logistic regression. Clinical outcomes were evaluated using the modified Rankin Scale (mRS) score at 90 days, the mortality at 90 days, and the occurrence of symptomatic intracranial hemorrhage within 48 h.ResultsAmong the 267 patients with distal BAO (222 patients in the EVT group and 45 patients in the SMT group), compared with the SMT group, the EVT group was associated with a favorable outcome (mRS 0–3; 40.1 vs. 15.6%; aOR 5.44; 95% CI, 1.68–17.66; P = 0.005) and decreased mortality (44.6 vs. 71.1%, aOR 0.32, 95% CI, 0.13–0.77; P = 0.012). In the EVT group, multivariable analysis showed that the initial National Institutes of Health Stroke Scale (NIHSS) score and posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS) were associated with favorable functional outcomes and mortality.ConclusionOur study suggests that, compared with SMT, EVT is technically feasible and safe for patients with distal BAO.

IntroductionAccording to the literature on anterior circulation, comorbid atrial fibrillation (AF) is not associated with a worse functional outcome, lower reperfusion rates, or higher rates of intracranial hemorrhage after mechanical thrombectomy (MT) compared to intravenous thrombolysis (IVT) or treatment with supportive care. However, data are limited for the effect of comorbid AF on procedural and clinical outcomes of acute basilar artery occlusion (ABAO) after MT. This study aimed to investigate the effect of atrial fibrillation on outcomes after MT and long-term ischemic recurrence in patients with ABAO.MethodsWe performed a registered study of the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR, which is registered in the Chinese Clinical Trial Registry, http://www.chictr.org.cn; ChiCTR1800014759) from January 2014 to May 2019, which included 647 patients who underwent MT for ABAO, 136 of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.ResultsOn multivariate analysis, AF predicted a shorter puncture-to-recanalization time, higher first-pass effect rate, and lower incidence of angioplasty and/or stenting (p < 0.01). AF had no effect on intracranial hemorrhage incidence [adjusted odds ratio (aOR), 1.093; 95% confidence interval (CI), 0.451–2.652], 90-day functional outcomes (adjusted common odds ratio, 0.915; 95% CI, 0.588–1.424), or mortality (aOR, 0.851; 95% CI, 0.491–1.475) after MT. The main findings were robust in the subgroup and 1-year follow-up analyses. Comorbid AF was the remaining predictor of ischemic recurrence (aOR, 4.076; 95% CI, 1.137–14.612).ConclusionsThe study revealed no significant difference in the safety and efficacy of MT for ABAO regardless of whether patients had comorbid AF. However, a higher proportion of patients with AF experienced ischemic recurrence within 1 year after MT.

Bromus inermis L. (commonly known as smooth bromegrass) is a grass species with high nutritional value, great palatability, cold tolerance, and grazing resistance, which has been widely cultivated for pasture and sand fixation in northern and northwestern China. Salt stress is a main environmental factor limiting growth and production of smooth bromegrass. In this study, we performed PacBio Iso-Seq to construct the first full-length transcriptome database for smooth bromegrass under 300 mM NaCl treatment at different time points. Third-generation full-length transcriptome sequencing yielded 19.67 G polymerase read bases, which were assembled into 355,836 full-length transcripts with an average length of 2,542 bp. A total of 116,578 differentially expressed genes were obtained by comparing the results of third-generation sequencing and second-generation sequencing. GO and KEGG enrichment analyses revealed that multiple pathways were differently activated in leaves and roots. In particular, a number of genes participating in the molecular network of plant signal perception, signal transduction, transcription regulation, antioxidant defense, and ion regulation were affected by NaCl treatment. In particular, the CBL-CIPK, MAPK, ABA signaling network, and SOS core regulatory pathways of Ca2+ signal transduction were activated to regulate salt stress response. In addition, the expression patterns of 10 salt-responsive genes were validated by quantitative real-time PCR, which were consistent with those detected by RNA-Seq. Our results reveal the molecular regulation of smooth bromegrass in response to salt stress, which are important for further investigation of critical salt responsive genes and molecular breeding of salt-tolerant smooth bromegrass.

BackgroundThis study aimed to investigate the association between the hyperdense basilar artery sign (HBAS) on non-enhanced computed tomography (CT) and clinical outcomes in patients with acute basilar artery occlusion (BAO) who underwent endovascular treatment (EVT).MethodsEligible patients who underwent EVT due to acute BAO between January 2014 and May 2019 were divided into two groups based on HBAS. HBAS was assessed by two neuroradiologists using five grades on nonenhanced CT. The primary outcome was a favorable functional outcome (defined as a modified Rankin Scale [mRS] of 0–3) at 90 days. Secondary outcomes included successful recanalization and mortality within 90 days.ResultsAmong 829 patients with BAO as assessed with CT angiography, magnetic resonance angiography, or digital subtraction angiography, 643 patients were treated with EVT. Of these, 51.32% (330/643) had HBAS. Patients with HBAS were older and had more severe neurological deficits and a higher frequency of atrial fibrillation than those without HBAS. There was no significant difference in favorable outcome (adjusted odds ratio [aOR]: 1.354, 95% confidence interval [CI]: 0.906–2.024; p = 0.14), successful recanalization (aOR: 0.926, 95% CI: 0.616-−1.393; p = 0.71), and mortality (aOR: 1.193, 95% CI: 0.839–1.695; p = 0.33) between patients with or without HBAS. Subgroup analysis showed that the HBAS predicted a favorable outcome in patients aged

Abstract Background Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib. Methods A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib. Results Compound heterozygous variants of TREX1 were observed in the patient’s genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient’s father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient’s mother. One of the proband’s elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement. Conclusions We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease.

Abstract Tumor metastasis remains an obstacle in cancer treatment and is responsible for most cancer-related deaths. Nm23-H1 is one of the first metastasis suppressor proteins discovered with the ability to inhibit metastasis of many cancers including breast, colon, and liver cancer. Although loss of Nm23-H1 is observed in aggressive cancers and correlated with metastatic potential, little is known regarding the mechanisms that regulate its cellular level. Here, we examined the mechanisms that control Nm23-H1 expression in breast cancer cells. Initial studies in aggressive MDA-MB-231 cells (expressing low Nm23-H1) and less invasive MCF-7 cells (expressing high Nm23-H1) revealed that mRNA levels correlated with protein expression, suggesting that transcriptional mechanisms may control Nm23-H1 expression. Truncational analysis of the Nm23-H1 promoter revealed a proximal and minimal promoter that harbor putative binding sites for transcription factors including CTCF and EGR1. CTCF and EGR1 induced Nm23-H1 expression and reduced cell migration of MDA-MB-231 cells. Moreover, CTCF and EGR1 were recruited to the Nm23-H1 promoter in MCF-7 cells and their expression correlated with Nm23-H1 levels. This study indicates that loss of Nm23-H1 in aggressive breast cancer is apparently caused by downregulation of CTCF and EGR1, which potentially drive Nm23-H1 expression to promote a less invasive phenotype.

Plastic electrodes are desirable for the rapid development of flexible organic electronics. In this article, a plastic electrode has been prepared by employing traditional conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) and plastic substrate polyethersulfone (PES). The completed electrode (Denote as HC-PEDOT:PSS) treated by 80% concentrated sulfuric acid (H2SO4) possesses a high electrical conductivity of over 2673 S/cm and a high transmittance of over 90% at 550 nm. The high conductivity is attributed to the regular arrangement of PEDOT molecules, which has been proved by the X-ray diffraction characterization. Temperature-dependent conductivity measurement reveals that the HC-PEDOT:PSS possesses both semiconducting and metallic properties. The binding force and effects between the PEDOT and PEI are investigated in detail. All plastic solar cells with a classical device structure of PES/HC-PEDOT:PSS/PEI/P3HT:ICBA/EG-PEDOT:PSS show a PCE of 4.05%. The ITO-free device with a structure of Glass/HC-PEDOT:PSS/Al4083/PM6:Y6/PDINO/Ag delivers an open-circuit voltage (VOC) of 0.81 V, short-circuit current (JSC ) of 23.5 mA/cm2, fill factor (FF) of 0.67 and a moderate power conversion efficiency (PCE) of 12.8%. The above results demonstrate the HC-PEDOT:PSS electrode is a promising candidate for all-plastic solar cells and ITO-free organic solar cells.

Abstract Background While anthocyanins are proven to be effective in inhibiting tumour cell proliferation, the underlying mechanisms remain unclear. This research aims to explore the glycosylation of anthocyanins in the tumour inhibitory effects and the potential mechanism. Methods The tumour inhibitory effect on mouse colon cancer cells (MC38) was examined by MTT and flow cytometric analyses. The inhibitory pathway of anthocyanin was explored by assessment of tumour cell mitochondrial membrane potential (MMP), the caspase-3 and caspase-9 activity, as well as the cell energy metabolism in terms of the glucose uptake, the NAD+/NADH ratio and the ATP level. Results We found that 500 μM bilberry anthocyanins extract (BAE) induced 48.1% mitochondrial damage, activated the downstream caspase cascade to form apoptotic bodies (caspase-3 activity increased by 169%, caspase-9 activity increased by 186%), and inhibited cell proliferation (survival rate: 55.97%, 24 h). In contrast, the same concentration of anthocyanidin (cyanidin) led to marginal mitochondrial damage (only 9.85%) and resulted in little inhibition of MC38 cells (survival rate: 86.84%, 24 h). For cells incubated with 500 μM BAE, reactive oxygen species (ROS) decreased by 53.8%, but the ratio of NAD+/NADH increased to 3.67, demonstrating that the mitochondrial damage was induced by blocking energy metabolism. Furthermore, cell energy metabolism is related to glucose uptake since the presence of 200 μM GLUT1 inhibitor substantially enhanced the inhibitory effects of cyanidin-3-O-glucoside (Cy-3-Glu) at 500 μM (survival rate: 51.08%, 24 h). Conclusions The study suggested that the glycosides of anthocyanins might handicap glucose transport and inhibit energy metabolism, which, in turn, led to mitochondrial damage and apoptosis of tumour cells.

Medicago falcata is one of the leguminous forage crops, which grows well in arid and semiarid region. To fully investigate the mechanism of drought resistance response in M. falcata, we challenged the M. falcata plants with 30% PEG-6000, and performed physiological and transcriptome analyses. It was found that, the activities of antioxidant enzymes (eg. SOD, POD, and CAT) and soluble sugar content were all increased in the PEG-treated group, as compared to the control group. Transcriptome results showed that a total of 706 genes were differentially expressed in the PEG-treated plants in comparison with the control. Gene enrichment analyses on differentially expressed genes revealed that a number of genes in various pathway were significantly enriched, including the phenylpropanoid biosynthesis (ko00940) and glycolysis/gluconeogenesis (ko00010), indicating the involvement of these key pathways in drought response. Furthermore, the expression levels of seven differentially expressed genes were verified to be involved in drought response in M. falcata by qPCR. Taken together, these results will provide valuable information related to drought response in M. falcata and lay a foundation for molecular studies and genetic breeding of legume crops in future research.

Abstract Background Cystic fibrosis (CF) is a rare autosomal recessive disorder caused by biallelic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The clinical features and mutation spectrum of CF have been well characterized in Caucasians, while limited studies were conducted in Chinese patients. Subjects and methods A total of 20 individuals from 19 families were diagnosed with CF in this study. We analyzed the clinical features and screened all coding exons of CFTR using a combination of Sanger sequencing and multiplex ligation-dependent probe amplification analysis. Results The median age at onset was 9.3 years in our cohort, while the median age at diagnosis was 19 years. The respiratory system was most frequently affected in this study: all patients (100%, 19/19) presented diffuse bronchiectasis and 61.1% (11/18) of patients showed a forced expiratory volume in 1 s below 80% predicted. Six patients (6/20, 30%) exhibited allergic bronchopulmonary aspergillosis (ABPA). Only 4 (4/20, 20%) patients presented pancreatic exocrine insufficiency (PI). Three adult male patients receiving examinations for congenital bilateral absence of the vas deferens were all found positive for the condition. A total of 22 distinct mutations were detected in this cohort, with the variant p.G970D as the most common variant (12/38 alleles, 31.6%). Four variants (p.Y109D, p.I203F, p.D572E, and exon 2–3 deletion) were novel, which expanded the mutation spectrum of Chinese CF patients. Conclusions Chinese CF patients showed different clinical features and a distinct CFTR mutation spectrum compared with Caucasians. There is a significant diagnosis delay, suggesting the current underdiagnosis of CF in China.

Question understanding is an extremely important part of the question and answer (Q&A) system, which is the basis of subsequent information retrieval and answer extraction. In order to improve the semantic understanding of question, we propose a method of understanding the question based on the combination of semantic element for Chinese language. Firstly, the method uses lexical and rules recognition to extract the semantic elements of questions and recognizes the functions according to the preprocessing pattern. Secondly, combining the dependency analysis tree structure of the question and the function type, it can produce the semantic elements. Finally, a normalized semantic expression was generated. We extract the user questions in Baidu-Zhidao as the test set. The result shows that the accuracy of the proposed method is 97.8%, so the semantics of the Chinese language questions can be effectively understood by this method.

IP protocol is the core of TCP/IP network layer. However, since IP address and its Domain Name are allocated and managed by a single agency, there are risks of centralization. The semantic overload of IP address also reduces its scalability and mobility, which further hinders the security. This paper proposes a co-governing Multi-Identifier Network (MIN) architecture that constructs a network layer with parallel coexistence of multiple identifiers, including identity, content, geographic information, and IP address. On the management plane, we develop an efficient management system using consortium blockchain with voting consensus, so the network can simultaneously manage and support by hundreds or thousands of nodes with high throughput. On the data plane, we propose an algorithm merging hash table and prefix tree (HTP) for FIB, which avoids the false-negative error and can inter-translate different identifiers with tens of billions of entries. Further, we propose a scheme to transport IP packets using CCN as a tunnel for supporting progressive deployment. We deployed the prototype of MIN to the largest operators' network in Mainland China, Hongkong and Macao, and demonstrated that the network can register identifier under co-governing consensus algorithm, support VoD service very well.

Abstract Background Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disease featured by lung cysts, spontaneous pneumothorax, fibrofolliculomas and renal tumors. The causative gene for BHDS is the folliculin (FLCN) gene and more than 200 mutations have been reported in FLCN, mostly truncating mutations. The aim of this study is to better characterize the clinical features and mutation spectrum of Chinese BHDS patients and to systematically evaluate the effects of non-truncating mutations on mRNA splicing pattern. Methods We enrolled 47 patients from 39 unrelated families with symptoms highly suggestive of BHDS after informed consent and detailed clinical data were collected. Exon sequencing followed by multiplex ligation-dependent probe amplification testing were applied for mutation screening. The effects of non-truncating mutations, including 15 missense mutations and 6 in-frame deletions, on mRNA splicing were investigated by minigene assays. Results A total of 24 FLCN germline variants were found in 39 patients from 31 distinct families. Out of these patients, 100% (36/36) presented with lung cysts and 58.3% (21/36) had experienced spontaneous pneumothorax. Seventeen mutation carriers had skin lesions (47.2%, 17/36) and 9 (30%, 9/30) had kidney lesions including 8 with renal cysts and 1 with renal hamartoma. Among all detected variants 14 (58.3%, 14/24) were novel, including 11 variants classified to be pathogenic and 3 variants of uncertain significance. None of 21 non-truncating mutations changed the mRNA splicing pattern of minigenes. Conclusions We found different clinical features of Chinese BHDS patients compared with Caucasians, with more lung cysts and pneumothorax but fewer skin lesions and malignant renal cancer. Chinese patients with BHDS also have a different mutation spectrum from other races. Non-truncating mutations in FLCN did not disrupt mRNA splicing pattern, in turn supporting the hypothesis that these mutations impair folliculin function by disrupting the stability of the FLCN gene product.

Background and Purpose: It is unknown the benefit of endovascular therapy (EVT) for progressive stroke in patients with basilar artery occlusion (BAO). The aim of this study was to compare the efficacy and safety of EVT with standard medical therapy (SMT) in a population of BAO patients with progressive stroke.Methods: The EVT for Acute Basilar Artery Occlusion Study (BASILAR) is a national prospective registry of consecutive patients with acute BAO within 24 h of symptom onset. According to the applied therapy, all patients were divided into SMT and EVT groups. Subsequently, the EVT group was divided into early (≤6 h) and late groups (>6 h) according to the time window. The efficacy outcome was favorable functional outcomes (modified Rankin Scale score ≤ 3) at 90 days. The safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage (sICH) after EVT.Results: The EVT cohort presented more frequently with a favorable functional outcome (adjusted odds ratio, 5.49; 95% confidence interval, 2.06–14.61, p = 0.01) and with a decreased mortality (adjusted odds ratio, 0.3; 95% confidence interval, 0.17–0.54, p < 0.001). What's more, EVT still safe (P = 0.584, P = 0.492, respectively) and effective (P = 0.05) in patients with progressive stroke when the treatment time window exceeds 6 h.Conclusions: EVT was more effective and safer than SMT for progressive stroke in patients with BAO. Besides, EVT remains safe and effective in patients with progressive stroke when the treatment time window exceeds 6 h. Predictors of desirable outcome in progressive stroke patients undergoing EVT included lower baseline NIHSS score, higher baseline pc-ASPECTs, successful recanalization and shorter puncture to recanalization time.

Background: To date, few data have been reported on clinical outcomes following interventions in elderly populations with acute basilar artery occlusion. Using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR), we evaluated the efficacy and safety of intervention and determined predictors of outcomes among elderly patients in China. Methods: Patients from January 2014 to May 2019 were dichotomized into elderly (75 years or older) and nonelderly patients (under 75 years). Pearson’s Chi-square test and multivariate logistic regression were performed to assess 90-day favorable functional outcome (defined as a modified Rankin scale score of 0–3), mortality and symptomatic intracranial hemorrhage between intervention and conservative cohorts in elderly patients. Results: Among the 829 patients in the BASILAR, 182 patients aged 75 years or older were analyzed. These patients were divided into intervention (127 patients) and conservative (55 patients) cohorts. Compared with the conservative cohort, the intervention cohort presented more frequently with a favorable functional outcome (28.3% versus 12.7%; p = 0.023) and with a decreased mortality (54.3% versus 76.4%; p = 0.005). There was no difference in symptomatic intracranial hemorrhage (4.7% versus 0, p = 0.235). Multivariate analysis indicated that intervention was associated with favorable functional outcome (adjusted odds ratio, 0.262; 95% confidence interval, 0.088–0.778, p = 0.016) and lower mortality (adjusted odds ratio, 0.257; 95% confidence interval, 0.109–0.606, p = 0.002). In the intervention cohort, initial National Institutes of Health Stroke Scale (NIHSS) score and occlusion site were associated with functional outcome, and initial NIHSS score and recanalization were associated with mortality. Conclusions: Although the overall outcome following intervention was worse with age, intervention was more effective and safer than conservative treatment for elderly Chinese patients with basilar artery occlusion. Predictors of desirable outcome in elderly patients undergoing intervention included lower initial NIHSS score, occlusion site and successful recanalization. Clinical Trial Registration-URL: http://www.chictr.org . Unique identifier: ChiCTR-1800014759

Doxorubicin (DOX) is a widely used first-line antitumor agent; however, acquired drug resistance and side effects have become the main challenges to effective cancer therapy. Herein, DOX is loaded into iron-rich metal–organic framework/tannic acid (TA) nanocomplex to form a tumor-targeting and acid-activatable drug delivery system (MOF/TA-DOX, MTD). Under the acidic tumor microenvironment, MTD simultaneously releases DOX and ferrous ion (Fe2+) accompanied by degradation. Apart from the chemotherapeutic effect, DOX elevates the intracellular H2O2 levels through cascade reactions, which will be beneficial to the Fenton reaction between the Fe2+ and H2O2, to persistently produce hydroxyl radicals (•OH). Thus, MTD efficiently mediates chemodynamic therapy (CDT) and remarkably enhances the sensitivity of chemotherapy. More encouragingly, the cancer cell killing efficiency of MTD is up to ~86% even at the ultralow equivalent concentration of DOX (2.26 μg/mL), while the viability of normal cells remained >88% at the same concentration of MTD. Taken together, MTD is expected to serve as drug-delivery nanoplatforms and •OH nanogenerators for improving chemo/chemodynamic synergistic therapy and reducing the toxic side effects.

Abstract Background Homoharringtonine (HHT) is a natural alkaloid with potent antitumor activity, but its precise mechanism of action is still poorly understood. Methods We examined the effect of HHT on alternative splicing of Bcl-x and Caspase 9 in various cells using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The mechanism of HHT-affected alternative splicing in these cells was investigated by treatment with protein phosphatase inhibitors and overexpression of a protein phosphatase. Results Treatment with HHT downregulated the levels of anti-apoptotic Bcl-xL and Caspase 9b mRNA with a concomitant increase in the mRNA levels of pro-apoptotic Bcl-xS and Caspase 9a in a dose- and time-dependent manner. Calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), significantly inhibited the effects of HHT on the alternative splicing of Bcl-x and Caspase 9, in contrast to okadaic acid, a specific inhibitor of PP2A. Overexpression of PP1 resulted in a decrease in the ratio of Bcl-xL/xS and an increase in the ratio of Caspase 9a/9b. Moreover, the effects of HHT on Bcl-x and Caspase 9 splicing were enhanced in response to PP1 overexpression. These results suggest that HHT-induced alternative splicing of Bcl-x and Caspase 9 is dependent on PP1 activation. In addition, overexpression of PP1 could induce apoptosis and sensitize MCF7 cells to apoptosis induced by HHT. Conclusion Homoharringtonine regulates the alternative splicing of Bcl-x and Caspase 9 through a PP1-dependent mechanism. Our study reveals a novel mechanism underlying the antitumor activities of HHT.

Abstract Background Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear. Methods The inhibitory effect of gigantol on Wnt/β-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic β-catenin were determined by Western blot analysis. The expression of Wnt target genes was analyzed using real-time PCR. Cell viability was measured with a MTT assay. The effect of gigantol on cell migration was examined using scratch wound-healing and transwell migration assays. Results Gigantol decreased the level of phosphorylated LRP6 and cytosolic β-catenin in HEK293 cells. In breast cancer MDA-MB-231 and MDA-MB-468 cells, treatment with gigantol reduced the level of phosphorylated LRP6, total LRP6 and cytosolic β-catenin in a dose-dependent manner, resulting in a decrease in the expression of Wnt target genes Axin2 and Survivin. We further demonstrated that gigantol suppressed the viability and migratory capacity of breast cancer cells. Conclusion Gigantol is a novel inhibitor of the Wnt/β-catenin pathway. It inhibits Wnt/β-catenin signaling through downregulation of phosphorylated LRP6 and cytosolic β-catenin in breast cancer cells.

To study the effect of the addition of potassium perchlorate (KClO _4 ) on the performance of nano thermites, Al/Bi _2 O _3 nano thermites with different mass fraction (wt%) of KClO _4 was made by ultrasonic dispersion method. Then, all samples were tested by SEM, DSC and rapid excitation ignition. DSC results showed Al/Bi _2 O _3 /10 wt%KClO _4 had the highest heat release. Compared with Al/Bi _2 O _3 , the heat release increased by 28.32%. The results of activation energy calculations showed Al/Bi _2 O _3 /30 wt%KClO _4 had the lowest activation energy (Ea). Its activation energy was reduced by 30%, mere about 149.17 KJ mol ^−1 . Finally, it can be seen from the combustion situation that the addition of KClO _4 reduced the intensity of burning. This work found a way to increase the heat release or reduce the activation energy of nano thermites by controlling the amount of KClO _4 added.

Herein, we report a flexible high-conductivity transparent electrode (denoted as S-PH1000), based on conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), and itsapplication to flexible semi-transparentsupercapacitors. A high conductivity of 2673 S/cm was achieved for the S-PH1000 electrode on flexible plastic substrates via a H2SO4 treatment with an optimized concentration of 80 wt.%. This is among the top electrical conductivities of PEDOT:PSS films processed on flexible substrates. As for the electrochemical properties,a high specific capacitance of 161F/g was obtained from the S-PH1000 electrode at a current density of 1 A/g. Excitingly, a specific capacitance of 121 F/g was retained even when the current density increased to 100 A/g, which demonstrates the high-rate property of this electrode. Flexible semi-transparent supercapacitors based on these electrodes demonstrate high transparency, over 60%, at 550 nm. A high power density value, over 19,200 W/kg,and energy density, over 3.40 Wh/kg, was achieved. The semi-transparent flexible supercapacitor was successfully applied topower a light-emitting diode.

To investigate the effect of the addition of poly (vinylidene fluoride) (PVDF) on nanothermites, Al/MoO _3 /PVDF energetic nanocomposites were prepared using electrospraying method. As a control group, Al/MoO _3 was also designed. Then, both samples were tested by FE-SEM, XRD and TG-DSC. TG-DSC results showed that the Al/MoO _3 /PVDF energetic nanocomposites released more than 934.0 J g ^−1 with two obvious exothermic peaks. Compared with the control group of 800.7 J g ^−1 heat, it changed the thermal performance to some extent. There were Mo _2 C among the residues products after the reaction via XRD. The activation energy (Ea) was analyzed using the Kissinger method under different heating rates by DSC. The addition of PVDF reduced the Ea of the thermites. To explore the combustion performance, a preliminary experiment was designed. The Al/MoO _3 /PVDF energetic nanocomposites were easier to ignite and the burning was more durable, which was significant in solid propulsion and applications requiring extended combustion time.

Solution-processed polymer solar cells (PSCs) have attracted dramatically increasing attention over the past few decades owing to their advantages of low cost, solution processability, light weight, and excellent flexibility. Recent progress in materials synthesis and devices engineering has boosted the power conversion efficiency (PCE) of single-junction PSCs over 17%. As an emerging technology, it is still a challenge to prepare solution-processed flexible electrodes for attractive flexible PSCs. Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) is one of the most promising candidates for electrodes due to its high conductivity (>4000 S/cm), excellent transmittance (>90%), intrinsically high work function (WF > 5.0 eV), and aqueous solution processability. To date, a great number of single-junction PSCs based on PEDOT:PSS electrodes have realized a PCE over 12%. In this review, we introduce the current research on the conductive complex PEDOT:PSS as well as trace the development of PEDOT:PSS used in electrodes for high performance PSCs and perovskite solar cells. We also discuss and comment on the aspects of conductivity, transmittance, work-function adjustment, film preparing methods, and device fabrications. A perspective on the challenges and future directions in this field is be offered finally.

When the Al/Ta/PTFE reactive material was sintered at 360 °C in a vacuum sintering furnace, it was found that the material reacted to form a soft fluffy white substance and carbon black. To explore the reaction process further, powder samples of pure PTFE, Al/PTFE, Ta/PTFE and Al/Ta/PTFE, and molded cylindrical specimens were prepared. A TG-DSC test was carried out on the thermal reaction of four reactive materials, and XRD phase analysis was conducted on the white product, formed by the sintering reaction and the residue of the TG-DSC test sample, based on which of the pyrolysis processes and reaction mechanisms were analyzed. The results show that Ta and PTFE could have a chemical reaction at sintering temperature (360 °C) to form soft and fluffy white material TaF3 and carbon black, which can overflow the surface of the specimen and cause cracking of the specimen, which is tightly pressed. Since no obvious exothermic peak showed up on the TG-DSC curve, the composition of the residue of TG-DSC sample at different temperatures was tested and TaF3 was detected in the residue at 350 °C and 360 °C, indicating that Ta began to react with PTFE at a temperature range of 340−350 °C. According to the chemical properties and product formation of Ta, it could be speculated that the reaction mechanism between Ta and PTFE involves the PTFE decomposing first, then the fluorine-containing gas product reacting with metal Ta. According to the temperature range of the reaction, it is estimated that PTFE starts to decompose before 500 °C, but it is not detected effectively by TG-DSC, and the introduction of Ta could also affect the decomposition process of PTFE.

To analyze the mechanical properties and reaction characteristics of Al-ZrH2-PTFE (aluminum-zirconium hydride-polytetrafluoroethylene) composites under quasi-static compression, five types of specimens with different ZrH2 contents (0%, 5%, 10%, 20% and 30%) were prepared by molding-vacuum sintering. The true stress-strain curves and reaction rates of the different specimens were measured using quasi-static compression. The specific reaction processes were recorded by a high-speed camera. The corresponding reaction products were characterized by the XRD phase analysis, the calorific value was tested by a Calorimeter, and the reaction mechanism was analyzed. According to the results, the strength of the composites increased first and then decreased with the increase in the content of ZrH2. It reached a maximum of 101.01 MPa at 5%. Violent reaction occurred, and special flames were observed during the reaction of the specimens with 5% ZrH2. With the increase in the content of ZrH2, the chemical reaction was hard to induce due to the reduction in strength and toughness of composites. The reaction mechanism of Al/ZrH2/PTFE reveals that high temperatures at crack tip induced the reaction of Al and PTFE. Subsequently, ZrH2 decomposed to release hydrogen and generate ZrC. Calorimetric experiment shows that the calorific value of Al/ZrH2/PTFE with 20% ZrH2 is higher than that of Al/PTFE. The findings verify the potential of ZrH2 as an energetic additive for the enhancement of strength and release of the energy of the composites.

Al-PTFE (aluminum-polytetrafluoroethene) is regarded as one of the most promising reactive materials (RMs). In this work, Ni (Nickel) was added to Al-PTFE composites for the purpose of improving the energy density and damage effect. To investigate the thermal behavior, mechanical properties and reaction characteristics of the Al-Ni-PTFE composites, an Al-PTFE mixture and an Al-Ni mixture were prepared by ultrasonic mixing. Six types of Al-Ni-PTFE specimens with different component mass ratios were prepared by molding sintering. Simultaneous thermal analysis experiments were carried out to characterize the thermal behavior of the Al-PTFE mixture and the Al-Ni mixture. Quasi-static compression tests were performed to analyze the mechanical properties and reaction characteristics of the Al-Ni-PTFE specimens. The results indicate that the reaction onset temperature of Al-Ni (582.7 °C) was similar to that of Al-PTFE (587.6 °C) and that the reaction heat of Al-Ni (991.9 J/g) was 12.5 times higher than that of Al-PTFE (79.6 J/g). With the increase of Ni content, the material changed from ductile to brittle and the strain hardening modulus and compressive strength rose first and then subsequently decreased, reaching a maximum of 51.35 MPa and 111.41 MPa respectively when the volume fraction of Ni was 10%. An exothermic reaction occurred for the specimens with a Ni volume fraction no more than 10% under quasi-static compression, accompanied by the formation of Ni-Al intermetallic compounds. In the Al-Ni-PTFE system, the reaction between Al and PTFE preceded the reaction between Al and Ni and the feasibility of increasing the energy density and damage effect of the Al-Ni-PTFE reactive material by means of Ni-Al reaction was proved.

Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and is related to various human diseases, such as cancer, Alzheimer’s disease (AD), cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases is still not clear, although multiple functions of CIB1 are modulated by interacting with numerous interacting partners. As a calcium binding protein, the roles of CIB1 in calcium signaling by binding calcium or modulating some key modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of CIB1 have been described in different aspects, including promoting tumor cell cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor cell migration and angiogenesis. In addition, multiple functions of CIB1, such as neural development, taste or gustation functions, and virus infection are also elucidated. These recent advances have significantly expanded our understanding of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in tumor progression.