Search

Interleukin-17 (IL-17) is involved in host defense against bacterial infection. Little is known about the role of IL-17 in A. baumannii-infected pneumonia. Our objective was to investigate the role of IL-17 in pulmonary A. baumannii infection in a mouse model. We infected C57BL/6 mice intra-tracheally (i.t.) with A. baumannii to establish pneumonia model and found A. baumannii infection elevated IL-17 expression in lungs. IL-17-deficient (Il17

Forest stock volume (FSV) is a key indicator for measuring forest quality, evaluating forest management capabilities, and the main factor for evaluating forest carbon sequestration levels. In this study, to achieve an accurate estimation of FSV, we used Ninth Beijing Forest Inventory data (FID), and Landsat 8 OLI and Sentinel-2 MSI imagery to establish FSV models. The performance of Landsat 8 and Sentinel-2 imagery data in estimating forest volume in Huairou District, Beijing, China was compared. The combination of Landsat 8 and Sentinel-2 satellite data was employed to create a new data source. Two variable selection methods, linear stepwise regression (LSR) and recursive feature elimination (RFE), were used to extract feature variables. The multiple linear regression(MLR) models, Back Propagation (BP) neural network models, and Random Forest (RF) models were employed to estimate forest volume in the study area based on the feature variables obtained from both data sources. The research results indicate (1) the Sentinel-2-based model achieved higher accuracy compared to the same model based on the Landsat 8 factor set. The correlation between the red-edge band of Sentinel-2 imagery and FSV is more significant than that of other characteristic variables used. Variables derived from the red-edge band have the potential to reduce model errors; (2) the estimation accuracy of the model can be significantly improved by using the RFE (Recursive Feature Elimination) method to select remote sensing feature variables. RFE is based on the importance ranking of all feature variables and selects the feature variables that contribute the most to the model. In the variable group selected by RFE, the texture features and the derived features from the red-edge band, such as SenB5, SenRVI, SenmNDVIre, and SenB5Mean, contribute the most to the improvement of model accuracy. Furthermore, in the optimal Landsat 8–Sentinel-2 RFE-RF model, where texture features are involved, the rRMSE is greatly reduced by 3.7% compared to the joint remote sensing RFE-RF model without texture features; (3) the MLR, BP, and RF models based on the modeling factor set established on Sentinel-2 have accuracy superior to the model accuracy established based on the modeling factor set of Landsat 8. Among them, the Random Forest (RF) method inverted by the recursive feature elimination (RFE) method using Sentinel-2A image has the best inversion accuracy effect (R2 = 0.831, RMSE = 12.604 m3 ha−1, rRMSE = 36.411%, MAE = 9.366 m3 ha−1). Comparing the performance of the models on the test set, the ranking is as follows, Random Forest (RF) model > Back Propagation (BP) neural network model > multiple linear regression (MLR) model. The feature variable screening based on the Random Forest’s recursive feature elimination (RFE) method is better than the linear stepwise regression (LSR). Therefore, the RFE-RF method based on the joint variables from Landsat 8 and Sentinel-2 satellite data to establish a new remote sensing data source provides the possibility to improve the estimation accuracy of FSV and provides reference for forest dynamic monitoring.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient

Surface modification techniques with plasma are widely investigated to improve the surface insulation capability of polymers under dry conditions, while the relationship between treatment method, surface physical and chemical properties, and wet flashover voltage is still unclear for inorganic ceramics. In this paper, the surface insulation properties of ceramics under wet conditions are improved using nanosecond-pulsed dielectric barrier discharge with PDMS as the precursor. The relationships between PDMS concentration and the water contact angle, dry and wet flashover voltages are obtained to acquire the optimal concentration. The surface charge dissipation test and surface physio-chemical property measurement with SEM, AFM, XPS are carried out to further explore the mechanism of surface insulation enhancement. The results show that film deposition with micron thickness and superhydrophobicity occurs at the PDMS concentration of 1.5%. The dry flashover voltage is increased by 9.6% due to the induction of deep traps, while the wet flashover voltage is increased by 66.7%. The gap between dry-wet flashover voltage is decreased by 97.4% compared with the untreated one due to the self-cleaning effect.

Sun-loving plants trigger the shade avoidance syndrome (SAS) to compete against their neighbors for sunlight. Phytochromes are plant red (R) and far-red (FR) light photoreceptors that play a major role in perceiving the shading signals and triggering SAS. Shade induces a reduction in the level of active phytochrome B (phyB), thus increasing the abundance of PHYTOCHROME-INTERACTING FACTORS (PIFs), a group of growth-promoting transcription factors. However, whether other factors are involved in modulating PIF activity in the shade remains largely obscure. Here, we show that SALT OVERLY SENSITIVE2 (SOS2), a protein kinase essential for salt tolerance, positively regulates SAS in Arabidopsis thaliana. SOS2 directly phosphorylates PIF4 and PIF5 at a serine residue close to their conserved motif for binding to active phyB. This phosphorylation thus decreases their interaction with phyB and posttranslationally promotes PIF4 and PIF5 protein accumulation. Notably, the role of SOS2 in regulating PIF4 and PIF5 protein abundance and SAS is more prominent under salt stress. Moreover, phyA and phyB physically interact with SOS2 and promote SOS2 kinase activity in the light. Collectively, our study uncovers an unexpected role of salt-activated SOS2 in promoting SAS by modulating the phyB-PIF module, providing insight into the coordinated response of plants to salt stress and shade.

SUMMARYGravity controls directional growth of plants, and the classical starch-statolith hypothesis proposed more than a century ago postulates that amyloplast sedimentation in specialized cells initiates gravity sensing, but the molecular mechanism remains mysterious. Here, we report that gravistimulation by reorientation triggers the Mitogen-Activated Protein Kinase (MAPK) signaling-mediated phosphorylation of LAZY proteins, the key regulators of gravitropism accumulated more on the lower side of the plasma membrane in columella cells in regular growthArabidopsis. Phosphorylation of LAZY increases its interaction with several TOC proteins on the surface of amyloplasts, facilitating the translocation of LAZY proteins from the plasma membrane to the amyloplasts. Amyloplast sedimentation subsequently guides LAZY to relocate to the new lower side of the plasma membrane in columella cells, where LAZY induces asymmetrical auxin distribution and differential growth. Together, this study provides a molecular interpretation for the starch-statolith hypothesis: the organelle movement-triggered molecular polarity formation.

Worker division of labor is predominant in social insects. The foraging (for) gene, which encodes cGMP-dependent protein kinase (PKG), has been implicated in the regulation of behavioral transitions in honeybees, but information regarding its function in other social insects is scarce.We investigated the role of the for (Sifor) gene in the red imported fire ant, Solenopsis invicta, and found that Sifor and PKG exhibited different expression patterns in different castes, body sizes, ages and tissues of fire ants, especially in foragers and nurses. Foragers displayed greater locomotor activity but showed no preference for larval or adult odors, whereas nurses showed lesser locomotor activity but had a strong preference for larval odors. We found that the expression of Sifor was significantly higher in the heads of foragers (compared to nurses). RNA interference-mediated Sifor knockdown in foraging workers induced behavioral transition of foragers toward the nurse phenotype characterized by reduced locomotor activity and a stronger preference for larval odors. By contrast, treating nurses with 8-Br-cGMP, an activator of PKG, resulted in behavioral transition toward the forager phenotype characterized by higher locomotor activity but reduced preference for larval odors.Our results suggest that Sifor plays a critical role in the behavioral transition between foragers and nurses of workers, which may be a promising target for RNAi-based management of worker caste organization in S. invicta. © 2022 Society of Chemical Industry.

The echinoderm microtubule associated protein‐like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non‐small‐cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)‐ALK rearrangement is extremely rare. The co‐occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1‐ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions after she acquired osimertinib resistance. Furthermore, we summarize 22 published cases of patients with lung adenocarcinoma with concurrent EGFR mutation and ALK rearrangement, including details of clinical characteristics, natural history, and pertinent therapy of this uncommon tumor subtype. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co‐alterations in the pre‐alectinib era and that ALK inhibition with crizotinib did not show more eye‐catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.

Macrophage infiltration and activation is a critical step during acute colitis. Redox-mediated activation of NLRP3 inflammasomes in macrophages plays a critical role in mediating colonic inflammatory responses. Rhein isolated from the rhizome of rhubarb exhibits anti-inflammatory effects in various diseases. However, its role in regulating acute colonic inflammation is unexplored. Here, we investigated the protective mechanisms of rhein during acute gut inflammation and its regulation of macrophage activation.Inhibitory effects of rhein on NLRP3 inflammasomes were evaluated in activated macrophages and a mouse model of colitis. Expression of inflammatory mediators, inflammasome complex and redox-related signalling were analysed by ELISA, Western blots, immunofluorescence staining, and qRT-PCR. The phenotype of macrophages was assessed by flow cytometry. Colonic inflammation was evaluated by histological analysis.Rhein significantly decreased IL-1β secretion via NLRP3 inflammasomes by disturbing their assembly in macrophages. Rhein also activated the Nrf2-HO1-NQO1 pathway and inhibited expression of Nox2 subunits and translocation to regulate redox balance. Moreover, rhein attenuated inflammatory responses by mediating macrophage polarization from M1 to M2 phenotype. NF-κB, AP-1, and MAPK signalling were also involved in improving inflammatory conditions by rhein. In mice with acute intestinal inflammation, rhein treatment attenuated clinical features and reduced macrophage infiltration into damaged tissue to alleviate colonic inflammation.Rhein regulated redox-mediated NLRP3 inflammasome activation to protect against acute colitis, by interfering with macrophage accumulation and polarization. These findings provide a promising strategy of novel compounds for regulating mucosal inflammation in gastrointestinal disorders.

Cytokines play vital roles in the pathogenesis of inflammatory bowel disease. IL17B is protective in the development of colitis. However, how IL17B regulates intestinal inflammation and what cells are regulated by IL17B is still unknown. Here, we aimed to illustrate the IL17B dependent cellular and molecular changes in colon tissue in a mouse colitis model. The results showed that IL17B expression in colon tissues was elevated in inflamed tissues than non-inflamed tissues of IBD patients. Wild type (WT) and Il17b deficient (Il17b-/-) mice were given 2.5% dextran sodium sulfate (DSS) water, and in some case, Il17b-/- mice were treated with recombinant mouse IL17B. IL17B deficiency resulted in severe DSS-induced colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokines in colon. Reconstitution of Il17b-/- mice with recombinant IL17B alleviated the severity of DSS-induced colitis. Single cell transcriptional analyses of CD45+ immune cells in colonic lamina propria revealed that loss of IL17B resulted in an increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages in colitis, which were confirmed by real-time PCR and flow cytometry. IL17B treatment also inhibited lipopolysaccharide-induced inflammation in bone marrow-derived macrophages and mice. IL17B inhibits colitis by regulating colonic myeloid cell response. It might represent a novel potential therapeutic approach to treat the colitis.

Endothelialization of the aneurysmal neck is essential for aneurysm healing after endovascular treatment. Mesenchymal stem cell (MSC)-seeded stents can promote aneurysm repair. investigated the biological effects of coated and uncoated nitinol intracranial stents seeded with MSCs on vascular cell and macrophage proliferation and inflammation. Two stent coatings that exert pro-aggregation effects on MSCs via different mechanisms examined: gelatin/polylysine (G/PLL), which enhances cell adhesion, and silk fibroin/SDF-1α (SF/SDF-1α), which enhances chemotaxis. aim to explore the feasibility of MSC-seeded coated stents in the treatment of intracranial aneurysms. The G/PLL coating provided the highest cytocompatibility and blood compatibility substrate for MSCs and vascular cells and promoted cell adhesion and proliferation. Moreover, it enhanced MSC secretion and regulation of vascular cell and macrophage proliferation and chemotaxis. Although the SF/SDF-1α coating promoted MSC secretion and vascular cell chemotaxis, it induced a greater degree of macrophage proliferation, chemotaxis, and secretion of pro-inflammatory factors. MSC-seeded stents coated with G/PLL may benefit stent surface endothelialization and reduce the inflammatory response after endovascular treatment of intracranial aneurysm. These effects may improve aneurysm healing and increase the cure rate. This article is protected by copyright. All rights reserved.

Phytochrome A (phyA) is the far-red (FR) light photoreceptor in plants that is essential for seedling de-etiolation under FR-rich environments, such as canopy shade. TANDEM ZINC-FINGER/PLUS3 (TZP) was recently identified as a key component of phyA signal transduction in Arabidopsis thaliana; however, how TZP is integrated into the phyA signaling networks remains largely obscure. Here, we demonstrate that ELONGATED HYPOCOTYL5 (HY5), a well-characterized transcription factor promoting photomorphogenesis, mediates FR light induction of TZP expression by directly binding to a G-box motif in the TZP promoter. Furthermore, TZP physically interacts with CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), an E3 ubiquitin ligase targeting HY5 for 26S proteasome-mediated degradation, and this interaction inhibits COP1 interaction with HY5. Consistent with those results, TZP post-translationally promotes HY5 protein stability in FR light, and in turn, TZP protein itself is destabilized by COP1 in both dark and FR light conditions. Moreover, tzp hy5 double mutants display an additive phenotype relative to their respective single mutants under high FR light intensities, indicating that TZP and HY5 also function in largely independent pathways. Together, our data demonstrate that HY5 and TZP mutually upregulate each other in transmitting the FR light signal, thus providing insights into the complicated but delicate control of phyA signaling networks.

Bio-based hard-carbon materials were attracted wide-ranging attention in environmental protection and energy conversion with the advantages of low cost as well as recyclability. In this work, three-dimensional hierarchical porous hard carbon materials were synthesized by using the world’s lightest commercial balsa wood as the carbon source and further activated with strong alkali and calcium chloride. The as-modified carbon material exhibited a larger specific surface area of 499.4 m2g−1 (compared to 283.2 m2g−1 before modification) with a wide range of macropores, mesopores, and micropores, which can shorten the distance of diffusion to the inner surface and provide fast transmission channels for K-ions, resulting in an obvious enhanced reversible specific capacity and rate performance compared to untreated one. This work provides a reference for the utilization of industrial waste balsa wood residues in large-scale energy system.

A facile synthetic strategy is devised to construct raspberry like gold nanoparticles (RbNPs) formed by gold nanoclusters wrapped around β-cyclodextrin functionalized gold nanoparticles (CD-AuNPs@AuNCs). An efficient and sensitive electrochemical sensor for the detection of Cr(VI) has been developed based on RbNPs. The sensing platform exhibits an excellent wide linear range (100 pg mL

Senolytics, drugs that kill senescent cells, have been proposed to improve the response to pro-senescence cancer therapies; however, this remains challenging due to a lack of broadly acting senolytic drugs. Using CRISPR/Cas9-based genetic screens in different senescent cancer cell models, we identify loss of the death receptor inhibitor cFLIP as a common vulnerability of senescent cancer cells. Senescent cells are primed for apoptotic death by NF-κB-mediated upregulation of death receptor 5 (DR5) and its ligand TRAIL, but are protected from death by increased cFLIP expression. Activation of DR5 signaling by agonistic antibody, which can be enhanced further by suppression of cFLIP by BRD2 inhibition, leads to efficient killing of a variety of senescent cancer cells. Moreover, senescent cells sensitize adjacent non-senescent cells to killing by DR5 agonist through a bystander effect mediated by secretion of cytokines. We validate this ‘one-two punch’ cancer therapy by combining pro-senescence therapy with DR5 activation in different animal models.

Background This study analyzed the safety and efficacy of Enterprise 2 stent-assisted coil embolization for wide-necked intracranial aneurysms by examining stent-vessel apposition, operative complications, embolization outcomes, and clinical outcomes. Methods We retrospectively reviewed the medical records of patients with wide-necked intracranial aneurysms who underwent Enterprise 2 stent-assisted coiling in our hospital from November 2018 to October 2019. Intraoperative VasoCT was performed immediately after stent release in a continuous cohort of patients to observe stent-vessel apposition. Patient demographic, clinical, and imaging data were recorded and analyzed. Results A total of 106 wide-necked aneurysms in 106 patients were treated. Stent release was successful in all patients. Twenty-one patients were enrolled consecutively for VasoCT scanning, and incomplete stent apposition was observed in 5 (23.8%). Perioperative complications occurred in 10 patients (9.4%): cerebral infarction in 6, intraoperative coil prolapse in 1, puncture site pseudoaneurysm in 1, deep vein thrombosis at multiple sites in 1, and transient brainstem mass effect in 1. Among the 95 aneurysms with angiographic follow-up, embolization was satisfactory (Raymond–Roy classifications I and II) in 89 (93.7%). Hyperlipidemia was an independent risk factor for incomplete aneurysm occlusion. At the last clinical follow-up, seven patients had a poor clinical outcome (modified Rankin Scale score ≥ 3). Independent risk factors for poor outcomes were preoperative subarachnoid hemorrhage at presentation and cerebral infarction. Conclusion Enterprise 2 stent-assisted coiling for treatment of wide-necked intracranial aneurysms showed good safety and efficacy; however, incomplete stent apposition can still occur in vessels with a large curvature. Preoperative subarachnoid hemorrhage at presentation and cerebral infarction are the main reasons for poor clinical outcomes after stent-assisted coil embolization.

Whispering-gallery-mode (WGM) cavity is important for exploring physics of strong light-matter interaction. Yet it suffers from the notorious radiation loss universally due to the light tunneling effect through the curved boundary. In this work, we propose and demonstrate an optical black hole (OBH) cavity based on transformation optics. The radiation loss of all WGMs in the ideal OBH cavity is completely inhibited by an infinite wide potential barrier. Besides, the WGM field in the OBH cladding is revealed to follow $$1/r^\alpha$$ 1 / r α decay rule based on conformal mapping, which is fundamentally different from the conventional Hankel-function distributions in a homogeneous cavity. Experimentally, a truncated OBH cavity is achieved based on the effective medium theory, and both the Q-factor enhancement and tightly confined WGM fields are measured in the microwave spectra which agree well with the theoretical results. The circular OBH cavity is further applied to the arbitrary-shaped cavities including single-core and multi-core structures with high-Q factor via the conformal mapping. The OBH cavity design strategy can be generalized to resonant modes of various wave systems, such as acoustic and elastic waves, and finds applications in energy harvesting and optoelectronics.

The energy crisis has aroused widespread concern, and the reform of energy structure is imminent. In the future, the energy structure will be dominated by the solar energy and other renewable energy sources. The solar concentrating technology as a promising method has been widely studied for collecting solar energy. However, the previous solar concentrating technologies suffer from some drawbacks, such as low focusing efficiency and large concentrating size. The Luneburg lens with highly efficient aberration-free focusing provides a new route for solar/energy concentrator. In this work, we designed a plane focal surface Luneburg lens (PFSLL) by transformation optics (TO). The PFSLL provides a relatively good focusing efficiency and concentration ratio of collection of energy. At the same time, it circumvents the disadvantage of curve surface of the classical Luneburg lens in device integration. Based on the reciprocity of electromagnetic waves, the PFSLL can also be applied to the antenna field to achieve broadband wide-angle scanning and highly directional radiation.

Hepatocellular carcinoma (HCC)—the most common form of liver cancer—is an aggressive malignancy with few effective treatment options1. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit2. Here, using a kinome-centred CRISPR–Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR) by lenvatinib treatment leads to feedback activation of the EGFR–PAK2–ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR. EGFR inhibition and lenvatinib treatment of liver cancer cells in vitro and in in vivo mouse models has potent anti-proliferative effects, and lenvatinib plus gefitinib treatment of 12 patients with advanced liver cancer resulted in meaningful clinical responses.

Due to the expansion of human production activities, toxic ammonia (NH3) is excessively released into the atmosphere, being a huge threat to human health and the natural environment. Therefore, it is of great significance to design an easy-synthesized gas-sensing material with both good room temperature sensitivity and selectivity for trace-level NH3 detection. Herein, we fabricate a chemiresistive NH3 gas sensor with enhanced performance based on Ni(OH)2/Ti3C2Tx hybrid materials. The Ni(OH)2/Ti3C2Tx hybrid materials are synthesized by an in-situ electrostatic self-assembly method. Attributed to the formation of interfacial heterojunctions and the modulation of carrier density, the Ni(OH)2/Ti3C2Tx hybrid sensor exhibits high response, outstanding repeatability, good selectivity and stability in low concentrations of NH3. Moreover, the Ni(OH)2/Ti3C2Tx hybrid sensor has a higher response to 10 ppm NH3 at the relative humidity of 40% and 60%, which makes it promising for applications in real complex environments with high humidity. Benefitting from the low power consumption and easy fabrication process, the Ni(OH)2/Ti3C2Tx hybrid sensor possesses a broad application prospect in the internet of things (IoT) environmental monitoring.

With the rapid development of various portable electronic devices, lithium ion battery electrode materials with high energy and power density, long cycle life and low cost were pursued. Vanadium-based oxides/sulfides were considered as the ideal next-generation electrode materials due to their high capacity, abundant reserves and low cost. However, the inherent low conductivity and ion diffusion coefficient limit their practical applications in lithium ion batteries. In recent years, vanadium-based electrode materials have been designed into various nanostructures through a variety of nanofabrication processes to overcome the electrochemical performance bottleneck caused by the above disadvantages due to the new properties of nanomaterials that cannot be achieved at the solid level. However, how to obtain high-performance vanadium-based electrode nanomaterials with controllable morphology and structure through low-cost and environmentally friendly processes is still a huge challenge. In this paper, the basic structure, modified morphologies and synthesis methods of vanadium-based electrode materials for lithium ion batteries were reviewed. In addition, the disadvantages, new challenges and future development direction of vanadium electrode materials were also discussed.

BackgroundVertebrobasilar dissecting aneurysms (VBDAs) with an intramural hematoma (IMH) usually cause symptoms because of mass effect and grow in size over time. Clinical outcomes are generally poor.ObjectiveThis study aimed to examine outcomes of reconstructive endovascular treatment (EVT) in patients with VBDAs with IMH. Safety and effectiveness were compared between flow diverters (FDs) and conventional stents.MethodsWe retrospectively analyzed the clinical and radiological data of 36 VBDAs with IMH in 36 patients who underwent EVT with either FDs or conventional stents from January 2012 to December 2020 at our institution.ResultsAmong the 36 study patients, 20 were treated with FDs and 16 with conventional stents. Incidence of procedure-related complications did not significantly differ between the two stents. IMH growth occurred after EVT in a significantly higher proportion of conventional stent group aneurysms (zero vs. 31.3% [5/16]; p = 0.012). Among the five aneurysms with IMHs that grew, all recurred. Change in IMH size after EVT was significantly lower in the FD group (−2.7 vs. +8.1%, p = 0.036). However, after the recurrent aneurysms were removed from the conventional stent group, change in IMH size did not significantly differ between the two groups (−2.7 vs. +1.0%, p = 0.332). The proportion of patients who experienced an improvement in mRS score after EVT was significantly higher in the FD group (60 vs. 25%, p = 0.036).ConclusionIMHs in VBDAs stop growing after successful reconstructive EVT. Although both FD and conventional stent treatment are effective, FD treatment may be superior based on clinical outcomes and effect on IMH size.

Super-focusing light using metamaterials and metasurfaces is of paramount importance in several applications, from integrated optics to microwave engineering and sensing. However, there are still some difficulties to realize broadband achromatic aberration highly efficient super-focusing from the far field to far field or quasi far field. In this Letter, based on conformal transformation optics, we propose a generalized conformal Luneburg lens (GCLL), which provides a new, to the best of our knowledge, strategy for quasi-far-field super-focusing with broadband (0.9–1.3 THz) achromatic aberration and high efficiency (above 60%). A relatively high numerical aperture (NA of 0.63) and sub-diffraction-limited resolution (FWHM of 0.45λ) are also obtained. The sample of the GCLL was designed using gradient metamaterials. The numerical simulation results verify that the focusing effects of the designed samples are consistent with the performance of the ideal GCLL.

Abnormal oncogenic signatures provide important clues regarding cancer prognosis and treatment. We analysed the variations in 189 oncogenic signature gene sets between normal and tumourous tissues from The Cancer Genome Atlas (TCGA) and found that the “CSR_LATE_UP” signature was the most upregulated oncogenic signature gene set in bladder cancer. Next, we developed a common serum response (CSR) risk score (CRS) model based on fibroblast CSR genes and systematically analysed the correlations of these genes or the CRSs with survival, previously reported molecular subtypes, clinicopathological features, cancer signalling pathways, chemotherapeutic responses, and the tumour microenvironment using TCGA and validation cohorts. The CRS could predict the malignant phenotype, chemotherapeutic efficacy, immune invasion, and disease prognosis. Inflammatory signalling pathways (e.g., inflammatory response, TNFA signalling via NFƘB, IFNα response, and IL2-STAT5 signalling) were markedly upregulated in patients with high CRS. Notably, the CSR-related gene ANLN was positively correlated with CD8+ immune cell infiltration, PD-L1 expression, and sensitivity to PD-L1 inhibitors and could thus provide guidance for clinical immunotherapy. This study highlights the crucial role of the CSR signature in bladder cancer and provides a CRS model for accurate predictions of the disease prognosis and chemotherapy and immunotherapy responses.

The sugars will eventually be exported transporters (SWEETs) gene family is a new type of sugar transporters, which plays an important role in plant growth and development, physiological metabolism, and abiotic stress. In this study, we used quantitative real-time PCR to analyze the expression of ZmSWEET15a gene in different organs of maize and under different abiotic stresses. The results showed that ZmSWEET15a was expressed in roots, stems, leaves, and grains, with the highest expression level in leaves, which was highly correlated with leaf development. Under the treatment of polyethylene glycol (PEG), NaCl, H(2)O(2), and abscisic acid stress, the expression of ZmSWEET15a was upregulated, while under the treatment of cold stress, the expression of ZmSWEET15a was inhibited. In sugar-specific experiments, we found that sucrose was the most effective carbon source for maize seed germination.The expression analysis of ZmSWEET15a in different carbon sources suggested that the expression of ZmSWEET15a was more likely to be induced by sucrose. Overexpression of ZmSWEET15a in maize plants could reduce the sucrose content in leaves and increase the sucrose content in grains. The heterologous expression of ZmSWEET15a in the yeast mutant strain SUSY7/ura indicated that ZmSWEET15a is a sucrose transporter and pH independent. This study provides new insight into sugar transport and carbohydrate partitioning in maize and other crops, and provide more genetic information for improving crop quality at the molecular level.

Herein, we report a microwave-assisted acid-induced post-treatment method for the formation of linker vacancies within Zr-based metal organic frameworks (Zr-MOFs). The number of linker vacancies can be easily regulated with this method by changing the concentration of the HCl solution and the duration of microwave irradiation. The optimized defective UiO-66 showed higher linker defects with a higher specific surface area and thermal stability. The results of the catalytic cyclization of citronella showed that the Zr-MOFs with more defects exhibited enhanced catalytic performance. This work may provide a new method for the creation of defective MOFs with high activity and stability.

Metastasis is the major reason for poor prognosis and high fatality in hepatocellular carcinoma (HCC). Due to the "Warburg effect", an acidic tumor microenvironment (TME) exists in solid tumors and plays a critical role in cancer metastasis. Thus, clarifying the mechanism underlying the acidic TME in tumor metastasis could facilitate the development of new therapeutic strategies for HCC. Anoikis resistance is one of the most important events in the early stage of cancer metastasis. Here, we report that acidic extracellular pH (pHe) promotes autophagy of HCC cells via the AMPK/mTOR pathway. We found that autophagy induced by acidity enhances anoikis resistance of HCC cells, which could be reversed by autophagy inhibitors. Furthermore, miR-3663-3p was downregulated by acidity, and overexpression of miR-3663-3p abolished acidic pHe-induced autophagy and anoikis resistance. In summary, acidic pHe enhances anoikis resistance of HCC cells by inducing autophagy, which is regulated by miR-3663-3p. Our findings provide new insight into how the acidic TME is involved in HCC progression.

BackgroundBasilar trunk and vertebrobasilar junction (BTVBJ) aneurysms have a poor prognosis and are challenging to treat.ObjectiveThis study aimed to evaluate the efficacy of reconstructive endovascular treatment for BTVBJ aneurysms and explore a treatment selection paradigm.MethodsClinical and angiographic data from 77 patients with 80 BTVBJ aneurysms who underwent endovascular treatment with flow diverters (FDs) or conventional stent-assisted coiling between January 2016 and December 2020 were retrospectively analyzed. Aneurysm characteristics and treatment outcomes were compared between treatment groups.ResultsAmong the 77 study patients, 34 (44.2%) were treated with FDs and 43 (55.8%) with conventional stent-assisted coiling. Overall, 72.7% of patients achieved favorable clinical outcome at follow-up. The rate of procedure-related complications was 23.4%. The aneurysm occlusion rate at last follow-up did not differ between the FD and conventional stent groups (79.2% vs. 77.1%, p = 0.854). Although the occlusion rate immediately after the procedure was lower in the FD group (29.4%), incidence of progressive occlusion was significantly higher (62.5 vs. 5.7%; p < 0.001). The proportion of patients with large and giant aneurysms (≥10 mm) was significantly higher in the FD group (70.6 vs. 34.8%; p = 0.002). In patients with large or giant aneurysms, favorable clinical outcome at last follow-up was achieved in 75% of patients in the FD group but only 43.8% of patients in the conventional stent group (p = 0.046). Moreover, the complication rate was lower in the FD group, but the difference was not significant (20.8 vs. 37.5%; p = 0.247). The same analyses were performed for patients with small aneurysms (ConclusionEndovascular treatment of small BTVBJ aneurysms using either FDs or conventional stents was feasible and effective. In patients with large or giant aneurysms, treatment using FDs achieved higher rates of occlusion and favorable clinical outcome at last follow-up than conventional stent-assisted coiling.

Ulcerative colitis (UC) is an autoimmune disease afflicting an increasing number of patients and increasing demands towards the development of efficacious and safe drugs. Recently, with increasing interest in alternative medicines, natural resources have become a hotspot for drug discovery against UC. In addition to being consumed as a food and spice, ginger is also widely used as a well-recognized gastrointestinal herbal medicine. With a long history in the treatment of digestive disorders, the potential of ginger in alleviating UC has been documented in several experimental models and clinical trials. However, as a major active constituent of ginger, ginger polysaccharides (GP) and its effect on UC has yet to be reported. In this study, GP was firstly separated and characterized. In a dextran sulfate sodium (DSS)-induced colitis mouse model, GP alleviated UC symptoms by inhibiting pro-inflammatory cytokines levels to regulate intestinal inflammation, repairing the intestinal barrier as indicated by occludin-1 and ZO-1, as well as regulating gut microbiota. Taking these results together, we believe GP could be an innovative option in developing functional foods or therapeutic agents for UC management.

Significance Metastasis generally leads to a dismal prognosis in bladder cancer (BLCA). The mechanical status of the cell membrane has been reported to reflect the potential of the metastatic capacity of cancer cells. However, the molecular profile and corresponding mechanical traits underlying BLCA metastasis remain largely elusive. Our study demonstrates the significance of cytoskeleton-associated protein 4 (CKAP4) in BLCA malignancy through aptamer selection, emphasizes the mechanical dominance of the central-to-peripheral gradient over simply softening or stiffening in cell migration, and shows the role of exosomes in mediating mechanical signaling in BLCA metastasis. Altogether, our work verifies the promising advantages of an aptamer-based approach in cancer research, which ranges from biomarker discovery to the elucidation of biological functions.

Treatment of advanced liver cancer still faces great challenges. Identification of tumor dependencies is important for developing novel therapeutic strategies for liver cancer. Here, we identified mitochondrial translation as a major vulnerability of liver cancer by genome-wide CRISPR screen. Targeting mitochondrial translation by tigecycline showed therapeutic potential in liver cancer. Then, a compounds screen was applied to identify MEK inhibitors as synergistic drugs to tigecycline-insensitive liver cancer cells. Mechanistically, sustained activation of EGFR-ERK1/2-MYC cascade conferred the insensitivity to tigecycline, which was mediated by enhanced secretion of EREG and AREG. Moreover, glycolytic enzymes, such as HK2 and PKM2, and mitochondrial one-carbon enzyme SHMT2 were upregulated to stimulate glycolysis and maintain mitochondrial function, respectively, in a MYC-dependent manner. Tigecycline in combination with MEK inhibitor trametinib or EGFR inhibitor gefitinib showed synergistic antitumor effect in vitro and in vivo. Thus, our study provides a potential therapeutic strategy for liver cancer.