A novel HIV-1-encoded microRNA enhances its viral replication by targeting the TATA box region

BACKGROUND: A lot of microRNAs (miRNAs) derived from viral genomes have been identified. Many of them play various important roles in virus replication and virus-host interaction. Cellular miRNAs have been shown to participate in the regulation of HIV-1 viral replication, while the role of viral-encoded miRNAs in this process is largely unknown. RESULTS: In this report, through a strategy combining computational prediction and deep sequencing, we identified a novel HIV-1-encoded miRNA, miR-H3. MiR-H3 locates in the mRNA region encoding the active center of reverse transcriptase (RT) and exhibits high sequence conservation among different subtypes of HIV-1 viruses. Overexpression of miR-H3 increases viral production and the mutations in miR-H3 sequence significantly impair the viral replication of wildtype HIV-1 viruses, suggesting that it is a replication-enhancing miRNA. MiR-H3 upregulates HIV-1 RNA transcription and protein expression. A serial deletion assay suggests that miR-H3 targets HIV-1 5′ LTR and upregulates the promoter activity. It interacts with the TATA box in HIV-1 5′ LTR and sequence-specifically activates the viral transcription. In addition, chemically-synthesized small RNAs targeting HIV-1 TATA box activate HIV-1 production from resting CD4(+) T cells isolated from HIV-1-infected patients on suppressive highly active antiretroviral therapy (HAART). CONCLUSIONS: We have identified a novel HIV-1-encoded miRNA which specifically enhances viral production and provide a specific method to activate HIV-1 latency

Phase management in single-crystalline vanadium dioxide beams

A systematic study of various metal-insulator transition (MIT) associated phases of VO2, including metallic R phase and insulating phases (T, M1, M2), is required to uncover the physics of MIT and trigger their promising applications. Here, through an oxide inhibitor-assisted stoichiometry engineering, we show that all the insulating phases can be selectively stabilized in single-crystalline VO2 beams at room temperature. The stoichiometry engineering strategy also provides precise spatial control of the phase configurations in as-grown VO2 beams at the submicron-scale, introducing a fresh concept of phase transition route devices. For instance, the combination of different phase transition routes at the two sides of VO2 beams gives birth to a family of single-crystalline VO2 actuators with highly improved performance and functional diversity. This work provides a substantial understanding of the stoichiometry-temperature phase diagram and a stoichiometry engineering strategy for the effective phase management of VO2

Altered Brain Structure and Functional Connectivity of Primary Visual Cortex in Optic Neuritis

Previous studies have revealed brain adaptations to injury that occurs in optic neuritis (ON); however, the mechanisms underlying the functional connectivity (FC) and gray matter volume (GMV) changes in ON have not been clarified. Here, 51 single attack ON patients and 45 recurrent attacks ON patients were examined using structural MRI and resting-state functional MRI (RS-fMRI), and compared to 49 age- and gender-matched healthy controls (HC). FC analysis with a seed in primary visual cortex (V1 area) was used to assess the differences among three groups. Whole brain GMV was assessed using voxel-based morphometry (VBM). Correlation analyses were performed between FC results, structural MRI and clinical variables. We found positive correlations between the Paced Auditory Serial Addition Test (PASAT) score and FC in V1 area with bilateral middle frontal gyrus. Disease duration is significantly negatively related to FC in V1 area with the left inferior parietal lobule. Compared to the HC, single attack ON patients were found to have decreased FC values in the frontal, temporal lobes, right inferior occipital gyrus, right insula, right inferior parietal lobule, and significant increased FC values in the left thalamus. Recurrent attacks ON patients had the same pattern with single attack ON. No significant differences were found in brain GMV among three groups. This study provides the imaging evidence that impairment and compensation of V1 area connectivity coexist in ON patients, and provides important insights into the underlying neural mechanisms of ON

Approaching Disorder-Tolerant Semiconducting Polymers

Doping has been widely used to control the charge carrier concentration in organic semiconductors. However, in conjugated polymers, n-doping is often limited by the tradeoff between doping efficiency and charge carrier mobilities, since dopants often randomly distribute within polymers, leading to significant structural and energetic disorder. Here, we screen a large number of polymer building block combinations and explore the possibility of designing n-type conjugated polymers with good tolerance to dopant-induced disorder. We show that a carefully designed conjugated polymer with a single dominant planar backbone conformation, high torsional barrier at each dihedral angle, and zigzag backbone curvature is highly dopable and can tolerate dopant-induced disorder. With these features, the designed diketopyrrolopyrrole (DPP)-based polymer can be efficiently n-doped and exhibit high n-type electrical conductivities over 120 S cm−1, much higher than the reference polymers with similar chemical structures. This work provides a polymer design concept for highly dopable and highly conductive polymeric semiconductors

Differential Selective Etching of Functional Groups Strategy for Preparation of Organic Hollow Porous Silica

In this study, different structural of organic hollow porous silica were prepared based on differential selective etching of functional groups strategy, using ammonia as catalyst, cetyltrimethylammonium bromide (CTAB) as pore-forming agent and emulsifier, cyano silica (CN-SiO2) or vinyl silica (V-SiO2) formed by hydrolysis condensation of 2-cyanoethyl triethoxysilane (CTES) or vinyl triethoxysilane (VTES) were used as cores, NH-SiO2 prepared by 3-aminopropyl triethoxysilane (APTES), SH-SiO2 prepared by mercaptopropyl trimethoxysilane (MPTMS) and UD-SiO2 prepared by urea-propyl triethoxysilane (UPTES) as shells, separately. The morphology and structure of the products were characterized by scanning electron microscopy(SEM) and transmission electron microscopy(TEM). The study results showed that CN-SiO2 as core was considered to be benefit for the preparation of organic hollow porous silica compared to V-SiO2 as core. In addition, core-shell structure obtained from CN-SiO2NH-SiO2 tend to be changed into hollow porous structure in alkaline condition on account of differential selective etching of functional groups strategy

Mapping CO₂ spatiotemporal transfers embodied in China's trade using a global dynamic network model endogenizing fixed capital

A systematic approach that accurately assesses carbon emissions is essential to design climate policies. To fully consider the impacts of the intertemporal dynamics of using the past-formed capital for future production, endogenizing capital as an input into carbon accounting system has been proposed, and lead to the reallocation of emissions. However, little is known about how this reallocation occur, i.e., how carbon flows from the past-formed capital to the products it is used to produce and to the consumers who purchase these products. Here, enabled by a global CO2 transfer network model with capital endogenization, we take China as an example to trace the full process of CO2 spatiotemporal transfer and re-assess CO2 footprints. China contributed more than 40% of the global capital-related CO2 emissions with only 14% of global capital consumption. China drove domestic and foreign CO2 emissions mainly through purchasing service products, while foreign regions outsourced an order of magnitude higher emissions to China by importing products such as electricity, machinery and equipment. Along temporal horizons, CO2 emitted in historical years contributed 87% of the total emissions embodied in China's capital consumption, while new-formed capital contained 5.50 Gt CO2 emissions, which will be attributed to the future. Based on this, China's dynamic CO2 footprint was re-assessed as 4.65 Gt, an increase of more than 1/4 over the traditional results. This increase comes mainly from service products directly consuming building structure, especially real estate and public administration services. This study provided new understanding of CO2 accounting and identified new hotspots for differentiated climate policies.</p

Baseline Brain Activity Changes in Patients With Single and Relapsing Optic Neuritis

Purpose: To investigate spontaneous brain activity amplitude alterations in single and relapsing optic neuritis (sON and rON, respectively) and their relationships with clinical variables.Methods: In total, 42 patients with sON, 35 patients with rON and 50 healthy volunteers were recruited. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) scans were acquired for all participants and compared to investigate the changes in the amplitude of low-frequency fluctuations (ALFFs) among the three groups. The relationships between the ALFFs in regions with significant differences in the groups and clinical variables, including the logarithm of minimal angle of resolution (LogMAR), Expanded Disability Status Scale (EDSS) score and disease duration, were further explored.Results: Compared with healthy volunteers, the sON and rON patients showed significantly decreased ALFFs in several regions of the occipital and temporal lobes (i.e., inferior occipital gyrus and superior temporal gyrus; corrected p &lt; 0.01 using AlphaSim). The sON patients showed significantly increased ALFFs in the left caudate and certain regions in the frontal lobes (i.e., medial frontal gyrus), whereas the rON patients showed increased ALFFs in the bilateral inferior temporal gyrus and left medial frontal gyrus (corrected p &lt; 0.01 using AlphaSim). Significantly decreased ALFFs were observed in the right inferior parietal lobule (IPL), left posterior cingulate and precuneus in the rON patients compared with those in the sON patients (corrected p &lt; 0.01 using AlphaSim). Significant correlations were observed between the disease duration and ALFF in the left middle temporal gyrus, left inferior occipital gyrus, right lingual gyrus and right IPL (p &lt; 0.05).Conclusion: Functional impairment and adaptation occurred in both the sON and rON patients. Impairment mainly involved the occipital cortex, and functional adaptions predominantly occurred in the frontal lobe. Functional damage was more severe in the rON patients than in the sON patients and correlated with the disease duration