The nitrate transporter NRT2.1 directly antagonizes PIN7-mediated auxin transport for root growth adaptation.

As a crucial nitrogen source, nitrate (NO3-) is a key nutrient for plants. Accordingly, root systems adapt to maximize NO3- availability, a developmental regulation also involving the phytohormone auxin. Nonetheless, the molecular mechanisms underlying this regulation remain poorly understood. Here, we identify low-nitrate-resistant mutant (lonr) in Arabidopsis (Arabidopsis thaliana), whose root growth fails to adapt to low-NO3- conditions. lonr2 is defective in the high-affinity NO3- transporter NRT2.1. lonr2 (nrt2.1) mutants exhibit defects in polar auxin transport, and their low-NO3--induced root phenotype depends on the PIN7 auxin exporter activity. NRT2.1 directly associates with PIN7 and antagonizes PIN7-mediated auxin efflux depending on NO3- levels. These results reveal a mechanism by which NRT2.1 in response to NO3- limitation directly regulates auxin transport activity and, thus, root growth. This adaptive mechanism contributes to the root developmental plasticity to help plants cope with changes in NO3- availability.

Rational design of self-amplifying virus-like vesicles with Ebola virus glycoprotein as vaccines.

As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

A Chimeric Classical Insect-Specific Flavivirus Provides Complete Protection Against West Nile Virus Lethal Challenge in Mice.

West Nile virus (WNV), an arthropod-borne flavivirus, can cause severe symptoms, including encephalitis, and death, posing a threat to public health and the economy. However, there is still no approved treatment or vaccine available for humans. Here, we developed a novel vaccine platform based on a classical insect-specific flavivirus (cISF) YN15-283-02, which was derived from Culicoides. The cISF-WNV chimera was constructed by replacing prME structural genes of the infectious YN15-283-02 cDNA clone with those of WNV and successfully rescued in Aedes albopictus cells. cISF-WNV was nonreplicable in vertebrate cells and nonpathogenic in type I interferon receptor (IFNAR)-deficient mice. A single-dose immunization of cISF-WNV elicited considerable Th1-biased antibody responses in C57BL/6 mice, which was sufficient to offer complete protection against lethal WNV challenge with no symptoms. Our studies demonstrated the potential of the insect-specific cISF-WNV as a prophylactic vaccine candidate to prevent infection with WNV.

Soluble Nanographene C222: Synthesis and Applications for Synergistic Photodynamic/Photothermal Therapy.

Nanographene C222, which consists of a planar graphenic plane containing 222 carbon atoms, holds the record as the largest planar nanographene synthesized to date. However, its complete insolubility makes the processing of C222 difficult. Here we addressed this issue by introducing peripheral substituents perpendicular to the graphene plane, effectively disrupting the interlayer stacking and endowing C222 with good solubility. We also found that the electron-withdrawing substituents played a crucial role in the cyclodehydrogenation process, converting the dendritic polyphenylene precursor to C222. After disrupting the interlayer stacking, the introduction of only a few peripheral carboxylic groups allowed C222 to dissolve in phosphate buffer saline, reaching a concentration of up to 0.5 mg/mL. Taking advantage of the good photosensitizing and photothermal properties of the inner C222 core, the resulting water-soluble C222 emerged as a single-component agent for both photothermal and photodynamic tumor therapy, exhibiting an impressive tumor inhibition rate of 96%.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

Can low-dose intravenous bevacizumab be as effective as high-dose bevacizumab for cerebral radiation necrosis?

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.

Identification, characterization, and expression analysis of WRKY transcription factors in Cardamine violifolia reveal the key genes involved in regulating selenium accumulation.

BACKGROUND: Cardamine violifolia is a significant Brassicaceae plant known for its high selenium (Se) accumulation capacity, serving as an essential source of Se for both humans and animals. WRKY transcription factors play crucial roles in plant responses to various biotic and abiotic stresses, including cadmium stress, iron deficiency, and Se tolerance. However, the molecular mechanism of CvWRKY in Se accumulation is not completely clear. RESULTS: In this study, 120 WRKYs with conserved domains were identified from C. violifolia and classified into three groups based on phylogenetic relationships, with Group II further subdivided into five subgroups. Gene structure analysis revealed WRKY variations and mutations within the CvWRKYs. Segmental duplication events were identified as the primary driving force behind the expansion of the CvWRKY family, with numerous stress-responsive cis-acting elements found in the promoters of CvWRKYs. Transcriptome analysis of plants treated with exogenous Se and determination of Se levels revealed a strong positive correlation between the expression levels of CvWRKY034 and the Se content. Moreover, CvWRKY021 and CvWRKY099 exhibited high homology with AtWRKY47, a gene involved in regulating Se accumulation in Arabidopsis thaliana. The WRKY domains of CvWRKY021 and AtWRKY47 were highly conserved, and transcriptome data analysis revealed that CvWRKY021 responded to Na2SeO4 induction, showing a positive correlation with the concentration of Na2SeO4 treatment. Under the induction of Na2SeO3, CvWRKY021 and CvWRKY034 were significantly upregulated in the roots but downregulated in the shoots, and the Se content in the roots increased significantly and was mainly concentrated in the roots. CvWRKY021 and CvWRKY034 may be involved in the accumulation of Se in roots. CONCLUSIONS: The results of this study elucidate the evolution of CvWRKYs in the C. violifolia genome and provide valuable resources for further understanding the functional characteristics of WRKYs related to Se hyperaccumulation in C. violifolia.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Topologically Localized Vibronic Excitations in Second-Layer Graphene Nanoribbons.

It is of fundamental importance to characterize the intrinsic properties, like the topological end states, in the on-surface synthesized graphene nanoribbons (GNRs), but the strong electronic interaction with the metal substrate usually smears out their characteristic features. Here, we report our approach to investigate the vibronic excitations of the topological end states in self-decoupled second-layer GNRs, which are grown using an on-surface squeezing-induced spillover strategy. The vibronic progressions show highly spatially localized distributions at the second-layer GNR ends, which can be ascribed to the decoupling-extended lifetime of charging through resonant electron tunneling at the topological end states. In combination with theoretical calculations, we assign the vibronic progressions to specific vibrational modes that mediate the vibronic excitations. The spatial distribution of each resolved excitation shows evident characteristics beyond the conventional Franck-Condon picture. Our work by direct growth of second-layer GNRs provides an effective way to explore the interplay between the intrinsic electronic, vibrational, and topological properties.

Probing σ-Aromaticity-Driven Ring Contraction of Metallabenzocyclobutadiene to Metallabenzocyclopropene.

Ring contraction of metallacyclobutadiene to metallacyclopropene is rare because of the increasing strain from a four-membered ring to a three-membered one. Here we demonstrate a new series of reactions of metallabenzocyclobutadiene to metallabenzocyclopropene via density functional theory calculations. The results suggest that these reactions are thermodynamically favorable ranging from -17.4 to -29.4 kcal mol-1, and a low reaction barrier (10.3 kcal mol-1) is achieved when the metal center is Ru and the ligands are one cyanide and one chloride. Further analysis suggests that a strengthened binding energy helps stabilize the transition state in the protonation process. The aromaticity during the reaction was investigated using the electron density of delocalized bonds (EDDB), isomerization stabilization energy, and isodesmic reactions. The EDDB shows that the π-conjugation is disrupted in the intermediate, and then σ-aromaticity is generated and dominant in the products. Our findings could be helpful for experimentalists in developing novel ring contraction reactions driven by aromaticity.

Improvement of electrothermal and photothermal properties of ultra-thin graphite film on oxygen plasma-treated polyimide substrate.

Graphene and its derivatives are widely used in the field of energy conversion and management due to their excellent physical and chemical properties. In this paper, ultra-thin graphite film (GF) with thickness of 100-150 nm prepared by chemical vapor deposition was transferred to oxygen plasma-treated polyimide (PI) substrate as flexible heating film. The electrothermal and photothermal properties of GF on PI substrates with different treatment time were studied. The experimental results show that the PI substrate pretreated by oxygen plasma can change the surface morphology of GF, increase its electrical conductivity and light absorption capacity, and significantly improve the electrothermal and photothermal properties of GF heater. Under the low applied voltage of 5 V (power density of 0.81 W cm-2), the surface temperature of GF on 40 min plasma-treated PI substrate can rise to 250 °C, which is nearly 50 °C higher than that of GF on untreated PI substrate. When 100 nm thick commercial multilayer graphene film (MLG) is used, plasma-treated PI substrate can increase the electric heating temperature of MLG by 70 °C. In terms of photothermal performance, the surface temperature of GF on 50 min plasma-treated PI substrate can reach 73 °C under one Sun irradiation, which is 8 °C higher than that on untreated substrate. The experimental results are in good agreement with the simulation research. Our strategy has important implications for the development of efficient and energy-saving graphene/graphite-based heating films for advanced electrothermal and photothermal conversion devices.

Bridged triphenylamine-based fluorescent probe for selective and direct detection of HSA in urine.

Human serum albumin (HSA) serves as a crucial indicator for therapeutic monitoring and biomedical diagnosis. In this study, a near infrared (NIR) fluorescent probe, termed BTPA, characterized a donor-π-acceptor (D-π-A) structure based on bridged triphenylamine (TPA) was developed. BTPA exhibited outstanding sensitivity and selectivity towards HSA among various analysts, with a remarkable 50-fold fluorescence enhancement with a significant Stokes shift (∼190 nm) and a wide linear detection range of 0-20 µM of HSA. Especially, BTPA displayed selectivity for discrimination of HSA from BSA. Job's Plot analysis suggested a 1:1 stoichiometry for the formation of the BTPA-HSA complex. Displacement assays and molecular docking demonstrated that BTPA binds to subdomain IB of HSA which could effectively avoid interference from most drugs. Besides, BTPA have good biocompatibility and could detect of exogenous HSA with a relatively low fluorescence background. For practical applications, BTPA was tested for detecting HSA levels in human urine without any pretreatment, showing detection capability in the range of 0-10 µM with a fast response (<30 s), a limit of detection (LOD) of 0.12 µM and good recoveries (81.7-92.9 %), highlighting the high performance of bridged triphenylamine-based probe BTPA.

Feasibility of vertical force-velocity profiles to monitor changes in muscle function following different fatigue protocols.

PURPOSE: This study aimed to explore the feasibility of vertical force-velocity (F-V) profiles to monitor changes in muscle function following different fatigue protocols. The between-day reliability of vertical F-V profiles and the acute effects of two fatigue protocols on the changes of lower limb muscle function were examined. METHODS: Twelve resistance trained males completed a preliminary session to determine their back squat one-repetition maximum (1RM). Afterwards, they randomly performed two experimental sessions that only differed in the fatigue protocol applied: heavy-load traditional (HLT; five repetitions at 80% 1RM) and light-load ballistic (LLB; five repetitions at 30% 1RM) squat protocols. Participants' vertical F-V profiles (maximum theoretical force [F0], maximum theoretical velocity [v0], and maximum power output [Pmax]) were calculated before and immediately after each fatigue protocol. RESULTS: F0, v0, and Pmax showed acceptable to good between-day reliability (coefficient of variation ≤ 4.4%; intraclass correlation coefficient ≥ 0.84). Both fatigue protocols promoted a comparable reduction in Pmax (-10.1% for HLT and -12.2% for LLB). However, the LLB squat protocol reduced more v0 (-9.7%) than F0 (-0.4%), while the HLT squat protocol reduced F0 (-8.4%) more than v0 (-4.1%). CONCLUSIONS: The vertical F-V profile can be used to monitor changes in muscle function given its acceptable between-day reliability and its high sensitivity to detect the acute effect of force-oriented and velocity-oriented fatigue protocols on specific maximal neuromuscular capacities.

Rehabilitation of Combined Hard and Soft Palate Defects with a Soft Relining Prosthesis: A Clinical Report.

It remains a significant challenge in prosthetic rehabilitation for combined hard and soft palate defects on account of two primary reasons. At first, conventional impressions can hardly get an accurate analogue and usually bring about a terrible experience for the patients. Secondly, conventional hard denture base resins used in obturator prostheses exhibit limitations in marginal sealing, undercut retention, and elastic buffering when in contact with the soft palate. This article presents a case where combined hard and soft palate defects were successfully and rapidly reconstructed by using digital intraoral impression technology and denture soft reline material.

Nanographene with a Nitrogen-Doped Cavity.

Nitrogen-doped cavities are pervasive in graphenic materials, and represent key sites for catalytic and electrochemical activity. However, their structures are generally heterogeneous. In this study, we present the synthesis of a well-defined molecular cutout of graphene featuring N-doped cavity. The graphitization of a macrocyclic pyridinic precursor was achieved through photochemical cyclodehydrochlorination. In comparison to its counterpart with pyridinic nitrogen at the edges, the pyridinic nitrogen atoms in this nanographene cavity exhibit significantly reduced basicity and selective binding to Ag+ ion. Analysis of the protonation and coordination equilibria revealed that the tri-N-doped cavity binds three protons, but only one Ag+ ion. These distinct protonation and coordination behaviors clearly illustrate the space confinement effect imparted by the cavities.

Helical Nanographenes Bearing Pentagon-Heptagon Pairs by Stepwise Dehydrocyclization.

The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs.

π-Extension of Multiple Resonance Core: Double Helical and Heptagon Embedded Nanographenes.

Multiple resonance (MR) boron-nitrogen doped polycyclic aromatic hydrocarbons (BN-PAHs) showed compelling thermally activated delayed fluorescence (TADF), surpassing those of their hydrocarbon analogs. However, the structural variety of π-extended BN-PAHs remains narrow. In this study, we synthesized three double helical BN-doped nanographenes (BN-NGs), 2a-2c, via the π-extension of the MR core. During the formation of 2a, a nanographene with one heptagon (1a) was obtained, whereas subsequent dehydrocyclization of the [6]helicene units within 2b-2c led to heptagon structures, yielding other two BN-NGs containing double heptagons (1b-1c). These BN-NGs (2a-2c and 1a-1c) showed pronounced redshifts of 100-190 nm compared to the parent MR core while preserving the TADF characteristics and prolonging the delayed fluorescence lifetime to the millisecond level. Furthermore, the integration of heptagon ring into 1a-1c expanded the conjugation, reduced the oxidation potentials, and yielded a more flexible framework compared to those of 2a-2c. The enantiomers of 2a-2c, 1a, and 1c were resolved and their chiroptical properties were studied. Notably, 1a and 1c exhibited the increased chiroptical dissymmetry factors.

Remote Ischemic Conditioning and Outcomes in Acute Ischemic Stroke With Versus Without Large Artery Atherosclerosis.

BACKGROUND: RICAMIS trial (The Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke. We conducted a post hoc analysis of RICAMIS to investigate whether large artery atherosclerosis (LAA) subtype contributed to the outcomes. METHODS: This is a post hoc analysis of the RICAMIS trial. Patients randomized to RIC group and Control group in full analysis set of RICAMIS were classified into LAA and non-LAA subtypes. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale score of 0 to 1. Compared with patients receiving usual care, we investigated the association of RIC effect with outcomes in stroke subtypes and the interaction between RIC effect and stroke subtypes. The primary analysis was adjusted analysis. RESULTS: Among 1773 patients, 516 were assigned to LAA subtype (229 in the RIC group and 287 in the control group) and 1257 to non-LAA subtype (633 in the RIC group and 624 in the control group). Median age was 65 years, and 34.2% were women. A higher proportion of primary outcome was found to be associated with RIC treatment in LAA subtype (adjusted risk difference, 11.4% [95% CI, 3.6%-19.2%]; P=0.004), but not in non-LAA subtype (adjusted risk difference, 4.1% [95% CI, -1.1% to 9.3%]; P=0.12). There was no significant interaction between RIC effect and stroke subtypes (P=0.12). CONCLUSIONS: Patients with LAA subtype may benefit from RIC after stroke with respect to excellent functional outcome at 90 days. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03740971.

Hexa-Branched Nanographenes with Large Two-Photon Absorption.

The conventional approach toward molecules with large two-photon absorption (TPA) involves donor-acceptor conjugation. Herein we show a new strategy involving the use of hexa-branched nanographenes. We synthesized two hexa-branched nanographenes, one with six benzoaceanthrylene arms fused to the coronene core and the other with six pyrenyl arms fused to the coronene core. Neither of these hexa-branched nanographenes has a donor-acceptor structure, yet they exhibited high TPA values of 3.6 × 103 and 1.9 × 104 GM, respectively, which are the highest values recorded for heteroatom-free hydrocarbon molecules. Theoretical analysis suggests that the fused branched structures are responsible for the large TPA cross-section. These findings illustrate the importance of the topology of the fused conjugated skeleton in TPA and provide an alternative structural design toward large TPA.

Synthesis and Interlayer Assembly of a Graphenic Bowl with Peripheral Selenium Annulation.

Pentagonal cyclization at the bay positions of armchair-edged graphenic cores can build molecular bowls without the destruction of hexagonal lattices. However, this synthesis remains challenging due to unfavorable strain and the multiple reactions required. Here, we show that a new type of graphenic molecular bowl with a depth of 1.7 Å and a diameter of 1.2 nm is constructed by sextuple Se annulation at the bay positions of armchair-edged hexa-peri-hexabenzocoronene. This graphenic bowl is functionalized with phenylseleno groups that stack into a discrete bilayer dimer in solution. Such a dimer exhibits high stability and survives in the gas phase after laser ablation. Strikingly, the asymmetric one-dimensional supramolecular columns of graphenic bowl with coherent stacking configuration are observed in the solid state, which results in a strong second harmonic generation with prominent polarization dependence. Our findings present a concise synthesis of a giant molecular bowl with a graphenic core and demonstrate the unique supramolecular assembly of extended graphenic bowls.