Time Division Colorful Multiplexing Based on Carbon Nanodots with Modifiable Colors and Lifetimes.

Optical multiplexing technology plays a crucial role in various fields such as data storage, anti-counterfeiting, and time-resolved biological imaging. Nevertheless, employing single-wavelength phosphorescence for multiplexing often results in spectral overlap among the emission peaks of various channels, which can precipitate crosstalk and misinterpretation in the information-decoding process, thereby compromising the integrity and precision of the encrypted data. This paper proposes a time-divided colorful multiplexing technology based on phosphorescent carbon nanodots with different colors and lifetimes. Using different luminescence colors to symbolize varying information levels helps achieve multitiered information encryption and storage. By modulation of the lifetime and the emission wavelength, intricate information can be encoded, thereby enhancing the intricacy and security of the encryption mechanism. By assigning different data bits to each color, more information can be encoded in the same physical space. This method enables higher-density information storage and fortifies encryption, ensuring the compactness and security of information.

Binding of the plant-derived toxin simplexin to bovine protein kinase C: insights from molecular dynamics.

Pimelea poisoning of cattle is toxicologically linked to the activation of bovine protein kinase C (PKC) by the plant-derived toxin simplexin. To understand the affinity of PKC for simplexin, we performed molecular dynamics (MD) studies of simplexin, simplexin analogues, and several other activators of PKC. Binding enthalpy calculations indicated that simplexin had the strongest affinity for PKCα-C1B among the activators studied. Key to simplexin's affinity is its ability to form more hydrogen bonds to PKC, compared to the other activators. The C-3 carbonyl group and C-20 hydroxyl group of simplexin were identified as especially important for stabilizing the PKC binding interaction. The hydrophobic alkyl chain of simplexin induces deep membrane embedding of the PKC-simplexin complex, enhancing the protein-ligand hydrogen bonding. Our findings align with previous experiments on structure-activity relationships (SAR) for simplexin analogues, and provide insights that may guide the development of interventions or treatments for Pimelea poisoning.

Digital economy and the synergistic governance of pollutants and carbon emissions: Facilitation or obstruction?

As an emerging force enabling high-quality economic development, digital economy (DE) still requires further investigation regarding its impact on synergistic governance of pollutants and carbon emissions (SGPCE). This study examines the impact of DE on SGPCE using two-way fixed effects model, intermediary effect model, and spatial Durbin model using provincial panel data from 2011 to 2020. The research reveals that: (1) DE has a significant promoting effect on SGPCE. (2) Enhancing the degree of green technology innovation is a crucial means of transmission for DE to propel SGPCE. (3) DE additionally exerts a constructive influence on SGPCE in adjacent regions, manifesting a spatial spillover effect. (4) Furthermore, DE demonstrates a notably heightened impact on SGPCE in the western region with respect to regional heterogeneity. Additionally, in the realm of dimension heterogeneity, the industrial digitization yields more favorable dividends for SGPCE compared to digital industrialization. The above conclusions provide novel insights and empirical evidence to validate the connection between DE and SGPCE. It also gives new policy recommendations for China to combat pollution prevention and climate warming under the wave of global digitization.

Visualization of Mesoscopic Conductivity Fluctuations in Amorphous Semiconductor Thin-Film Transistors.

Charge transport in amorphous semiconductors is considerably more complicated than the process in crystalline materials due to abundant localized states. In addition to device-scale characterization, spatially resolved measurements are important to unveiling electronic properties. Here, we report gigahertz conductivity mapping in amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors by microwave impedance microscopy (MIM), which probes conductivity without Schottky barrier's influence. The difference between the dc and microwave conductivities reflects the efficacy of the injection barrier in an accumulation-mode transistor. The conductivity exhibits significant nanoscale inhomogeneity in the subthreshold regime, presumably due to trapping and release from localized states. The characteristic length scale of local fluctuations, as determined by the autocorrelation analysis, is about 200 nm. Using a random-barrier model, we can simulate the spatial variation of the potential landscape, which underlies the mesoscopic conductivity distribution. Our work provides an intuitive way to understand the charge transport mechanism in amorphous semiconductors at the microscopic level.

Ultrafast and Electrically Tunable Rabi Frequency in a Germanium Hut Wire Hole Spin Qubit.

Hole spin qubits based on germanium (Ge) have strong tunable spin-orbit interaction (SOI) and ultrafast qubit operation speed. Here we report that the Rabi frequency (fRabi) of a hole spin qubit in a Ge hut wire (HW) double quantum dot (DQD) is electrically tuned through the detuning energy (ϵ) and middle gate voltage (VM). fRabi gradually decreases with increasing ϵ; on the contrary, fRabi is positively correlated with VM. We attribute our results to the change of electric field on SOI and the contribution of the excited state in quantum dots to fRabi. We further demonstrate an ultrafast fRabi exceeding 1.2 GHz, which indicates the strong SOI in our device. The discovery of an ultrafast and electrically tunable fRabi in a hole spin qubit has potential applications in semiconductor quantum computing.

Dearomative Intramolecular (4+3) Cycloadditions of Thiophenes.

Unexpectedly facile dearomative intramolecular (4+3) cycloadditions of thiophenes with epoxy enolsilanes, providing sulfur-bridged cycloadducts, are reported. A total of fifteen thiophene substrates have been found to undergo (4+3) cycloaddition smoothly to produce endo and exo (4+3) adducts in yields of up to 83 % with moderate to good diastereoselectivity. Complete conservation of enantiomeric purity was observed when the optically enriched epoxide was used. The desulfurizing transformations of the sulfur-bridged skeleton of the cycloadducts provide functionalized 6,7-fused bicyclic frameworks consisting of 1,3-cycloheptadiene subunits. Density functional theory calculations reveal the origins of the facile dearomatization of thiophenes in these (4+3) cycloadditions.

A Direct Comparison of Theta Power and Frequency to Speed and Acceleration.

Decades of hippocampal neurophysiology research have linked the hippocampal theta rhythm to voluntary movement. A consistent observation has been a robust correlation between the amplitude (or power) and frequency of hippocampal theta and running speed. Recently, however, it has been suggested that acceleration, not running speed, is the dominating influence on theta frequency. There is an inherent interdependence among these two variables, as acceleration is the rate of change in velocity. Therefore, we investigated theta frequency and amplitude of the local-field potential recorded from the stratum pyramidale, stratum radiatum, and stratum lacunosum moleculare of the CA1 subregion, considering both speed and acceleration in tandem as animals traversed a circular task or performed continuous alternation. In male and female rats volitionally controlling their own running characteristics, we found that running speed carries nearly all of the variability in theta frequency and power, with a minute contribution from acceleration. These results contradicted a recent publication using a speed-clamping task, where acceleration and movement are compelled through the use of a bottomless car (Kropff et al., 2021a). Therefore, we reanalyzed the speed-clamping data replicating a transient increase in theta frequency during acceleration. Compared with track running rats, the speed-clamped animals exhibited lower velocities and acceleration values but still showed a stronger influence of speed on theta frequency relative to acceleration. As navigation is the integration of many sensory inputs that are not necessarily linearly related, we offer caution in making absolute claims regarding hippocampal physiology from correlates garnered from a single behavioral repertoire.SIGNIFICANCE STATEMENT A long-standing, replicable observation has been the increase of hippocampal theta power and frequency with increasing running speed. Recently, however, an experimental approach that clamps the running speed of an animal has suggested that acceleration is the dominant influence. Therefore, we analyzed data from freely behaving rats as well as data from the speed-clamping experiment. In unrestrained behavior, speed remains the dominant behavioral correlate to theta amplitude and frequency. Positive acceleration in the speed-clamp experiment induced a transient increase in theta frequency and power. However, speed retained the dominant influence over theta frequency, changing with velocity in both acceleration and deceleration conditions.

Enhancing Crystallization in Hybrid Perovskite Solar Cells Using Thermally Conductive 2D Boron Nitride Nanosheet Additive.

Controlling crystallization and grain growth is crucial for realizing highly efficient hybrid perovskite solar cells (PSCs). In this work, enhanced PSC photovoltaic performance and stability by accelerating perovskite crystallization and grain growth via 2D hexagonal boron nitride (hBN) nanosheet additives incorporated into the active perovskite layer are demonstrated. In situ X-ray scattering and infrared thermal imaging during the perovskite annealing process revealed the highly thermally conductive hBN nanosheets promoted the phase conversion and grain growth in the perovskite layer by facilitating a more rapid and spatially uniform temperature rise within the perovskite film. Complementary structural, physicochemical, and electrical characterizations further showed that the hBN nanosheets formed a physical barrier at the perovskite grain boundaries and the interfaces with charge transport layers, passivating defects, and retarding ion migration. As a result, the power conversion efficiency of the PSC is improved from 17.4% to 19.8%, along with enhanced device stability, retaining ≈90% of the initial efficiency even after 500 h ambient air storage. The results not only highlight 2D hBN as an effective additive for PSCs but also suggest enhanced thermal transport as one of the pathways for improved PSC performance by 2D material additives in general.

Recent advances of two-dimensional material additives in hybrid perovskite solar cells.

Perovskite solar cells (PSCs) have become one of the state-of-the-art photovoltaic technologies due to their facile solution-based fabrication processes combined with extremely high photovoltaic performance originating from excellent optoelectronic properties such as strong light absorption, high charge mobility, long free charge carrier diffusion length, and tunable direct bandgap. However, the poor intrinsic stability of hybrid perovskites under environmental stresses including light, heat, and moisture, which is often associated with high defect density in the perovskite, has limited the large-scale commercialization and deployment of PSCs. The use of process additives, which can be included in various subcomponent layers in the PSC, has been identified as one of the effective approaches that can address these issues and improve the photovoltaic performance. Among various additives that have been explored, two-dimensional (2D) materials have emerged recently due to their unique structures and properties that can enhance the photovoltaic performance and device stability by improving perovskite crystallization, defect passivation, and charge transport. Here, we provide a review of the recent progresses in 2D material additives for improving the PSC performance based on key representative 2D material systems, including graphene and its derivatives, transitional metal dichalcogenides, and black phosphorous, providing a useful guideline for further exploiting unique nanomaterial additives for more efficient and stable PSCs in the near future.

Tunable Electronic Transport of New-Type 2D Iodine Materials Affected by the Doping of Metal Elements.

2D iodine structures under high pressures are more attractive and valuable due to their special structures and excellent properties. Here, electronic transport properties of such 2D iodine structures are theoretically studied by considering the influence of the metal-element doping. In equilibrium, metal elements in Group 1 can enhance the conductance dramatically and show a better enhancement effect. Around the Fermi level, the transmission probability exceeds 1 and can be improved by the metal-element doping for all devices. In particular, the device density of states explains well the distinctions between transmission coefficients originating from different doping methods. Contrary to the "big" site doping, the "small" site doping changes transmission eigenstates greatly, with pronounced electronic states around doped atoms. In non-equilibrium, the conductance of all devices is almost weaker than the equilibrium conductance, decreasing at low voltages and fluctuating at high voltages with various amplitudes. Under biases, K-big doping shows the optimal enhancement effect, and Mg-small doping exhibits the most effective attenuation effect on conductance. Contrastingly, the currents of all devices increase with bias linearly. The metal-element doping can boost current at low biases and weaken current at high voltages. These findings contribute much to understanding the effects of defects on electronic properties and provide solid support for the application of new-type 2D iodine materials in controllable electronics and sensors.

Clinicians' practices and attitudes regarding advance care planning in mainland China: A multicenter cross-sectional survey.

OBJECTIVES: This study aims to explore clinicians' practices and attitudes regarding advance care planning (ACP) in mainland China. METHODS: This study was a multicenter cross-sectional survey. Clinicians from tertiary hospitals in Beijing, Guangxi, and Inner Mongolia were invited to participate in the study. A questionnaire was formulated based on related literature to obtain information including demographic characteristics, and practices and attitudes toward ACP. RESULTS: The total number of participants included 285 clinicians. The data response rate was 84.57%. Most of the clinicians had an inadequate understanding of ACP. Only a few clinicians had experience in participating or witnessing an ACP or related end-of-life discussions. Among 285 clinicians, 69.82% of clinicians were willing to introduce ACP to patients. Two hundred and thirty-eight (83.51%) clinicians wanted more education on ACP. Almost all clinicians believed that patients had the right to know about their diagnosis, prognosis, and available care options. Most clinicians (82.11%) regarded that ACP was partially feasible in mainland China. If clinicians had a serious illness, almost everyone was willing to find out their true health status and decide for themselves, and 81.40% wanted to institute an ACP for themselves. The biggest barriers to the use of ACP in mainland China were cultural factors. Statistical analysis revealed that some or good understanding level (P = 0.0052) and practical experience (P = 0.0127) of ACP were associated with the positive willingness. SIGNIFICANCE OF RESULTS: ACP is still in its infancy in mainland China. Clinicians had inadequate understanding and minimal exposure to ACP. Most clinicians recognized the value and significance of ACP and had a positive attitude toward ACP. Clinicians need to be provided with education and training to promote their ACP practices. Culturally appropriate ACP processes and documents need to be developed based on Chinese culture and Chinese needs.

Characterizing Pairwise U-Turn Behavior in Fish: A Data-Driven Analysis.

We applied the time-series clustering method to analyze the trajectory data of rummy-nose tetra (Hemigrammus rhodostomus), with a particular focus on their spontaneous paired turning behavior. Firstly, an automated U-turn maneuver identification method was proposed to extract turning behaviors from the open trajectory data of two fish swimming in an annular tank. We revealed two distinct ways of pairwise U-turn swimming, named dominated turn and non-dominated turn. Upon comparison, the dominated turn is smoother and more efficient, with a fixed leader-follower relationship, i.e., the leader dominates the turning process. Because these two distinct ways corresponded to different patterns of turning feature parameters over time, we incorporated the Toeplitz inverse covariance-based clustering (TICC) method to gain deeper insights into this process. Pairwise turning behavior was decomposed into some elemental state compositions. Specifically, we found that the main influencing factor for a spontaneous U-turn is collision avoidance with the wall. In dominated turn, when inter-individual distances were appropriate, fish adjusted their positions and movement directions to achieve turning. Conversely, in closely spaced non-dominated turn, various factors such as changes in distance, velocity, and movement direction resulted in more complex behaviors. The purpose of our study is to integrate common location-based analysis methods with time-series clustering methods to analyze biological behavioral data. The study provides valuable insights into the U-turn behavior, motion characteristics, and decision factors of rummy-nose tetra during pairwise swimming. Additionally, the study extends the analysis of fish interaction features through the application of time-series clustering methods, offering a fresh perspective for the analysis of biological collective data.

High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection.

Bloodstream infections (BSIs) caused by Pseudomonas aeruginosa are associated with a high mortality rate in the clinic. However, the fitness mechanisms responsible for the evolution of virulence factors that facilitate the dissemination of P. aeruginosa to the bloodstream are poorly understood. In this study, a transcriptomic analysis of the BSI-associated P. aeruginosa clinical isolates showed a high-level expression of cell-surface signaling (CSS) system Hxu. Whole-genome sequencing and comparative genomics of these isolates showed that a mutation in rnfE gene was responsible for the elevated expression of the Hxu-CSS pathway. Most importantly, deletion of the hxuIRA gene cluster in a laboratory strain PAO1 reduced its BSI capability while overexpression of the HxuIRA pathway promoted BSI in a murine sepsis model. We further demonstrated that multiple components in the blood plasma, including heme, hemoglobin, the heme-scavenging proteins haptoglobin, and hemopexin, as well as the iron-delivery protein transferrin, could activate the Hxu system. Together, these studies suggested that the Hxu-CSS system was an important signal transduction pathway contributing to the adaptive pathogenesis of P. aeruginosa in BSI.

Structure-Based Discovery of a Novel Class of Small-Molecule Pure Antagonists of Integrin αVß3.

Inhibitors of integrin αVß3 have therapeutic promise for a variety of diseases. Most αVß3-targeting small molecules patterned after the RGD motif are partial agonists because they induce a high-affinity, ligand-binding conformation and prime the receptor to bind the ligand without an activating stimulus, in part via a charge-charge interaction between their aspartic acid carboxyl group and the metal ion in the metal-ion-dependent adhesion site (MIDAS). Building upon our previous studies on the related integrin αIIbß3, we searched for pure αVß3 antagonists that lack this typical aspartic acid carboxyl group and instead engage through direct binding to one of the coordinating residues of the MIDAS metal ion, specifically ß3 E220. By in silico screening of two large chemical libraries for compounds interacting with ß3 E220, we indeed discovered a novel molecule that does not contain an acidic carboxyl group and does not induce the high-affinity, ligand-binding state of the receptor. Functional and structural characterization of a chemically optimized version of this compound led to the discovery of a novel small-molecule pure αVß3 antagonist that (i) does not prime the receptor to bind the ligand and does not induce hybrid domain swing-out or receptor extension as judged by antibody binding and negative-stain electron microscopy, (ii) binds at the RGD-binding site as predicted by metadynamics rescoring of induced-fit docking poses and confirmed by a cryo-electron microscopy structure of the compound-bound integrin, and (iii) coordinates the MIDAS metal ion via a quinoline moiety instead of an acidic carboxyl group.

Sparse Group Lasso: Optimal Sample Complexity, Convergence Rate, and Statistical Inference.

We study sparse group Lasso for high-dimensional double sparse linear regression, where the parameter of interest is simultaneously element-wise and group-wise sparse. This problem is an important instance of the simultaneously structured model - an actively studied topic in statistics and machine learning. In the noiseless case, matching upper and lower bounds on sample complexity are established for the exact recovery of sparse vectors and for stable estimation of approximately sparse vectors, respectively. In the noisy case, upper and matching minimax lower bounds for estimation error are obtained. We also consider the debiased sparse group Lasso and investigate its asymptotic property for the purpose of statistical inference. Finally, numerical studies are provided to support the theoretical results.

Optimal High-order Tensor SVD via Tensor-Train Orthogonal Iteration.

This paper studies a general framework for high-order tensor SVD. We propose a new computationally efficient algorithm, tensor-train orthogonal iteration (TTOI), that aims to estimate the low tensor-train rank structure from the noisy high-order tensor observation. The proposed TTOI consists of initialization via TT-SVD [1] and new iterative backward/forward updates. We develop the general upper bound on estimation error for TTOI with the support of several new representation lemmas on tensor matricizations. By developing a matching information-theoretic lower bound, we also prove that TTOI achieves the minimax optimality under the spiked tensor model. The merits of the proposed TTOI are illustrated through applications to estimation and dimension reduction of high-order Markov processes, numerical studies, and a real data example on New York City taxi travel records. The software of the proposed algorithm is available online (https://github.com/Lili-Zheng-stat/TTOI).

Natural occurrence of broad bean wilt virus 2 on Mirabilis jalapa in China.

Mirabilis jalapa Libosch. is an annual ornamental herbaceous plant. Its leaves and roots are used as a traditional folk medicine that function in clearing heat and detoxifying, promoting blood circulation, regulating menstruation, and nourishing kidney (Annapoorani et al. 2014; Liu et al. 2020; Wang et al. 2018). Broad bean wilt virus 2 (BBWV-2), which belongs to the family Secoviridae, is transmitted by aphid in a non-persistent manner in the nature (Kondo et al. 2005) and mainly damages Vicia faba, pepper, yam and spinach (He et al. 2021). The leaves of M. jalapa on the campus showed shrinking (Supplementary Fig. 1A), yellowing (Supplementary Fig. 1B), mosaic (Supplementary Fig. 1D & 1E), and the whole plant had stunted and rough (Supplementary Fig. 1A & 1C) symptoms in the autumn of 2021. Eight plants (S21-S28) with these symptoms were harvested for total RNA extraction, siRNA mixture purification, and siRNA library made (NEBNext® Ultra™ II RNA Library Prep Kit for Illumina®, NEB, UK). The high-throughput siRNA sequencing with pair-end method was performed on Illumina Hiseq 2000 platform (Sangon, Shanghai, China). The raw sequencing data was treated with the Illumina's CASAVA pipeline (version 1.8). The adaptor was removed and the reads were mostly distributed in 21-24 nt length area (Supplementary Fig. 2A). The contigs (∼12,500, Length > 350 bp) were obtained by de novo assembling with the Velvet Software 0.7.31 (k = 17), then the BLASTN was preformed against GenBank database. Surprisingly, 237 contigs showed significant nucleotide sequence similarities to the genome of BBWV-2. To determine the incidence of BBWV-2 to M. jalapa in campus garden, twenty-eight leaf samples were randomly collected from the garden. Leave extract and total RNA of the sample were tested for BBWV-2 by ELISA (Agdia, USA, SRA46202/0096) and RT-PCR assay, respectively. Twenty-two samples were infected compared with the positive control, and their readings of ELISA were above or parallel to the positive control (Supplementary Fig. 2B∼2D). The coding sequence (1,395 bp) of BBWV-2 movement protein (MP) was amplified by a specific pair of primers (Supplementary Table S1) according to the contigs, the results indicated that the 22 out of 28 samples (78.6%) tested positive for BBWV-2 by both ELISA and RT-PCR (Supplementary Fig. 2E). The MP fragment of BBWV-2 obtained from one of the sample was purified by TIANgel Midi Purification Kit (Tiangen, Beijing, China) and then cloned into pMD19-T (TaKaRa, Dalian, China) vector. Ten separate clones were selected and sequenced (Sangon, Shanghai, China) after PCR verification. The obtained sequences (GenBank accession No. OM416039) were analyzed by BLASTN and bioEdit software (version 7.2.3). According to the phylogenetic tree constructed by BBWV-2 MP sequences (Supplementary Fig. 3), the obtained MP sequences (OM416039, ON677747, and ON677748) were most related to the BBWV-2 MP sequences that from pepper (GenBank accession No. JX183228.1), they share the nucleotide identity of 84.87%. To determine the occurrence and distribution of BBWV-2 in other areas, another twenty-two samples were randomly collected for RT-PCR in different regions of Jiangsu Province, China (Supplementary Table S2). The BBWV-2 infection rate was 76.0% in the M. jalapa. In sum, this is the first report of BBWV-2 naturally infecting M. Jalapa in China.

Predicted Mode of Binding to and Allosteric Modulation of the µ-Opioid Receptor by Kratom's Alkaloids with Reported Antinociception In Vivo.

Pain management devoid of serious opioid adverse effects is still far from reach despite vigorous research and development efforts. Alternatives to classical opioids have been sought for years, and mounting reports of individuals finding pain relief with kratom have recently intensified research on this natural product. Although the composition of kratom is complex, the pharmacological characterization of its most abundant alkaloids has drawn attention to three molecules in particular, owing to their demonstrated antinociceptive activity and limited side effects in vivo. These three molecules are mitragynine (MG), its oxidized active metabolite, 7-hydroxymitragynine (7OH), and the indole-to-spiropseudoindoxy rearrangement product of MG known as mitragynine pseudoindoxyl (MP). Although these three alkaloids have been shown to preferentially activate the G protein signaling pathway by binding and allosterically modulating the µ-opioid receptor (MOP), a molecular level understanding of this process is lacking and yet important for the design of improved therapeutics. The molecular dynamics study and experimental validation reported here provide an atomic level description of how MG, 7OH, and MP bind and allosterically modulate the MOP, which can eventually guide structure-based drug design of improved therapeutics.

MiR-132 down-regulates high glucose-induced ß-dystroglycan degradation through Matrix Metalloproteinases-9 up-regulation in primary neurons.

Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post-synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of ß-dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; ß-dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long-term period, microRNA-132 (miR-132) would be down-regulated in neurons. Matrix Metalloproteinases-9 (MMP-9) mRNA, as a target of miR-132, could be up-regulated; higher expression and overlay activity of MMP-9 protein could increase ß-DG protein degradation. In this way, ß-DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes-induced cognitive dysfunction.

DDAH-1, via regulation of ADMA levels, protects against ischemia-induced blood-brain barrier leakage.

Dimethylarginine dimethylamino hydrolase-1 (DDAH-1) is an important regulator of nitric oxide (NO) metabolism that has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, its role in cerebral ischemia still needs to be elucidated. Herein, we examined the expression of DDAH-1 in the brain of rat by double-label immunofluorescence staining. DDAH-1 knock-out (DDAH-1-/-) and wild-type rats underwent middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, neurological scores, TTC staining and TUNEL assay were used to evaluate neurological damages. 3 and 7-days infarct outcomes were also shown. Blood-brain-barrier (BBB) permeability was examined via Evans blue extravasation and tight junction (TJ) proteins expression and mRNA levels by western blot and RT-qPCR. The levels of plasma asymmetric dimethylarginine (ADMA), NO and ADMA in brain tissue were also assessed. In addition, supplementation of L-arginine to DDAH-1-/- rats was used to explore its role in regulating NO. DDAH-1 was abundantly distributed in cerebral cortex and basal nuclei, and mainly expressed in neurons and endothelial cells. DDAH-1-/- rats showed aggravated neurological damage and BBB disruption, including decrease of TJ proteins expression but indistinguishable mRNA levels after MCAO/R. DDAH-1 depletion and neurological damages were accompanied with increased ADMA levels and decreased NO concentrations. The supplementation with L-arginine partly restored the neurological damages and BBB disruption. To sum up, DDAH-1 revealed to have a protective role in ischemia stroke (IS) and IS-induced leakage of BBB via decreasing ADMA level and possibly via preventing TJ proteins degradation.