HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Two isotropic pitches were prepared by air blowing and nitrogen distillation method using ethylene tar (ET) as a raw material. And correspondent carbon fibers were obtained through conventional melt spinning, stabilization and carbonization. The structures and properties of resultant pitches and fibers were characterized and their differences were discussed in this work. The results showed that introduction of the oxygen by air blowing method could quickly increase the yield and softening point of pitch. Moreover, the air blown pitch (ABP) composed of linear methylene chains of aromatic molecules while the nitrogen distilled pitch (NDP) mainly contained polycondensed aromatic rings, which was due to the oxygen containing functional groups existed in ABP could impede order stack of pitch molecules and form methylene bridge structure, instead of aromatic condensed structure like NDP. Meanwhile, the spinnability of ABP was not decreased even containing 2.31 wt% oxygen. In contrast, ABP had narrower molecular weight distribution, which contributed to better stabilization properties and higher tensile strength of carbon fiber. The tensile strength of carbon fibers from ABP was reached to 860 MPa with fiber diameter of about 10 μm, which was higher than that of NDP-derived carbon fibers of 640 MPa.

In this study, changes in the microstructure of coal tar pitch during successive processes, including pyrolysis, polycondensation, and crystallization, were examined in connection with the resulting variations in structure factors, as measured by XRD analysis, and functional groups, as confirmed by FTIR spectroscopy. To this end, four zones were defined based on variations in crystallinity, which were indicated by d002 and Lc. Each zone was further characterized by interpreting crystallinity development in relation to changes in functional groups and specimen height. At around 400 °C, polycondensation occurred as the C-Har and C-Hal peaks decreased in intensity. These peak reductions coincided with the formation of mesophase spheres, resulting in enhanced crystallinity. Subsequently, at around 500 °C, the peak intensity of C-H and COOH decreased, which was attributed to the release of large amounts of gasses. This led to sharp volume changes and a temporary reduction in crystallinity. All these results suggest that changes in the functional groups of coal tar pitch at lower temperatures (600 °C or less) during the carbonization process are closely associated with variations in its crystallinity. The major findings of the present study provide valuable insights for designing highly effective processes in the manufacturing of synthetic graphite blocks using CTP as a binder material, including by selecting appropriate temperature ranges to minimize volume expansion and crystallinity degradation and determining the lowest possible carbonization temperature to ensure adequate binder strength.

Pulverized coal pyrolysis based on solid heat carrier has a huge advantage in high tar yield. In this study, pyrolysis experiments of pulverized coal were conducted in a lab-scale fluidized bed reactor at 650 ℃, utilizing char as the solid heat carrier. The influence of mass ratio of char to coal (RATIO) was investigated. Results show that the incorporation of solid heat carrier of char significantly enhanced the initial reaction in coal pyrolysis, resulting in increasing yields of tar and gas but reducing one of char. The yield of tar maximally reached 148.80-262.22% of the Gray-King analysis value at the RATIO of 14.52 g/g. As the RATIO increased, the tar contained more light component content, indicating that incorporating solid heat carriers improved the tar quality. These findings offer significant insights for the design of fluidized bed pyrolysis unit utilizing char as solid heat carrier.

Economists have long been interested in examining inflation-growth nexus. Nevertheless, the nature of their relationship and the optimal level of inflation threshold for economic growth have still remained controversial in both theoretical and empirical works. Accordingly, this study investigates the existence of threshold effects of inflation on economic growth in Ethiopia over the period 1975-2018 using a Two-regime Threshold Auto-regressive (TAR) model. The study mainly departs from previous works since it estimates sector-specific inflation threshold level in food and non-food sectors. Our preliminary analyses clearly reveal that inflation in food sector has become more volatile, less-persistent and key contributor to the general inflation as compared to its non-food counterpart. Further, The TAR model results and robustness checks indicate the existence of inflation threshold in a range of 9-10%. In particular, the threshold level for food inflation is 10% and 8% for non-food inflation. In all cases, our results robustly confirm growth-detrimental effects of inflation after the threshold levels. After all, this study suggests the need for considering specific behaviors of food and non-food prices, and implementing appropriate fiscal and monetary policies to bring inflation down to a single-digit level.

Amyotrophic Lateral Sclerosis (ALS) is an irreversible neurodegenerative disease with no known cure. Recent studies suggest a strong metabolic component in ALS pathogenesis and have shown an inverse relationship between leptin levels and ALS progression, although the effects of leptin as a treatment have not yet been studied. Therefore, we aim to examine whether the acute treatment with leptin has beneficial effects on brain pathology and cognitive function in the transgenic TDP43A315T line of ALS. Mice were treated intranasally (IN) with 0.03mg/kg of leptin or vehicle (VH) daily for 7 days. Data showed a progressive decline in body weight and motor coordination in TDP43A315T mice. Moreover, Lep-treated TDP43A315T mice showed an earlier disease onset, along with an improvement in motor performance. Altered levels of some of the adipokines and metabolic proteins studied were found in TDP43A315T mice, which were differently expressed among Lep-treated and VH-treated animals. Furthermore, some correlations were found among the serum levels of this proteins in WT and TDP43A315T mice. As far as we know, this is the first pilot study to provide evidence of the therapeutic effect of leptin treatment in a mice model of ALS, although further studies are needed to expound on the underlying mechanisms.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

In this study, graphite, the most stable form of carbon, was examined for its hexagonal crystalline structure with specific dimensions (ao=2.46 Ǻ; co=6.70 Ǻ). Its framework comprises parallel carbon atom planes forming regular hexagons (side length 1.415 Ǻ) and 120° angles between adjacent atoms. Two structural variations exist: hexagonal symmetry (1-2-1-2-1-2 planes) and rhomboidal symmetry (1-2-3-1-2-3 planes). The research aimed to produce high-density graphite utilizing carbonaceous raw materials. Graphite-based materials often exhibit high porosity, necessitating additional treatments. The study successfully obtained mesophase tar pitch (yield: 45%), a pivotal raw material, and high-density graphite. The resulting graphite underwent characterization for physical properties (apparent and real density, porosity and compression strength), demonstrating conformity with existing literature data.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.