RESUMEN
HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R1 and R3 groups. The most potent and selective TAR RNA binder was a3 with R1 = OH, R2 = H and R3 = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.
Asunto(s)
Complejos de Coordinación , Transcriptasa Inversa del VIH , VIH-1 , ARN Viral , Inhibidores de la Transcriptasa Inversa , Rutenio , Rutenio/química , VIH-1/efectos de los fármacos , VIH-1/enzimología , Humanos , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Transcriptasa Inversa del VIH/química , Relación Estructura-Actividad , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , ARN Viral/metabolismo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/química , Duplicado del Terminal Largo de VIH/efectos de los fármacosRESUMEN
As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.
Asunto(s)
Transcriptasa Inversa del VIH , VIH-1 , Inhibidores de la Transcriptasa Inversa , Rutenio , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/metabolismo , Ligandos , VIH-1/enzimología , VIH-1/efectos de los fármacos , Rutenio/química , Rutenio/farmacología , ARN Viral/metabolismo , ARN Viral/química , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Compuestos de Espiro/metabolismo , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Estructura Molecular , Humanos , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Duplicado del Terminal Largo de VIH , Sitios de UniónRESUMEN
Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.
Asunto(s)
Carga Global de Enfermedades , Infecciones por VIH , Humanos , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Infecciones por VIH/epidemiología , Infecciones por VIH/mortalidad , Masculino , Femenino , Anciano , Carga Global de Enfermedades/tendencias , Asia/epidemiología , Estudios de Cohortes , Incidencia , Años de Vida Ajustados por Discapacidad , Costo de EnfermedadRESUMEN
We present the case of a 26-year-old woman with recurrent episodes of severe pain, weakness, and atrophy in her bilateral upper extremities during pregnancy and puerperium. She reported 2 similar episodes at ages 5 and 10 years, after which she fully recovered. On examination, we observed significant atrophy in her bilateral upper extremity muscles with decreased strength. Needle electromyography (EMG) revealed neurogenic damage in her bilateral upper limbs. The patient's clinical manifestations and auxiliary examination suggested a brachial plexopathy. Metabolic and immune factors that may occur during pregnancy and puerperium were evaluated. We also screened for paraneoplastic, neoplastic, and genetic factors. Finally, a hereditary form of disease was considered. This case emphasizes the importance of early diagnosis and avoidance of triggers.
Asunto(s)
Dolor , Periodo Posparto , Humanos , Femenino , Embarazo , Preescolar , Niño , Adulto , Atrofia , Razonamiento Clínico , Extremidad SuperiorRESUMEN
The total suspended particulate (TSP) samples were collected in the Qingdao coastal region and over the Yellow and Bohai Sea from June to July in 2016. The diurnal and nightly TSP samples were also continuously collected in the Qingdao coastal region from August 6 to 15. The concentrations of dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), dissolved total nitrogen (DTN), dissolved total phosphorus (DTP), total nitrogen (TN), and total phosphorus (TP) in the TSP samples were analyzed. Results showed that the concentrations of different forms of nitrogen and phosphorus in Qingdao were higher than those over the Yellow and Bohai Sea during the same sampling period. The contribution of dissolved N was similar to that of insoluble N to TN in Qingdao, with the ratio of DTN to TN of 56%. However the DTN was the dominant contributor of TN over the Yellow and Bohai Sea, accounting for 72% of TN on average. The inorganic nitrogen was the dominant species of DTN in Qingdao and over the Yellow and Bohai Sea (YBS), accounting for 67% and 75% of DTN, respectively. The contribution of dissolved P to TP was similar to that of insoluble P to TP in Qingdao and over the Yellow and Bohai Sea, and the DTP accounted for 49% and 58% of TP in Qingdao and over YBS, respectively. The ratio of IP to DTP was slightly higher than that of OP, with values of 56% and 59% in Qingdao and over the YBS, respectively. The origin of the air mass affected the concentrations and compositions of nitrogen and phosphorus in the aerosols. The concentrations of DIN, dissolved organic nitrogen (DON), TN, DIP, and dissolved organic phosphorus (DOP) in the aerosols from southern air mass were higher than those from northern and marine air masses. The concentration of DON in the diurnal aerosol samples was similar to that in the nightly samples; however, the concentrations of DIN and TN were higher in the diurnal aerosols than those in the nightly aerosols. The DTN was the dominant species of TN in the diurnal and nightly aerosol samples, accounting for 79% of TN on average. Inorganic nitrogen was the dominant species of DTN in the diurnal and nightly aerosols. The ratio of DIN to DTN decreased from 70% in diurnal samples to 61% in nightly samples. The concentrations of DIP were close to that of DOP in the diurnal and nightly aerosols; however, the concentrations of TP were higher in the diurnal aerosols than in the nightly ones. The insoluble P was the dominant form of TP in the aerosols, accounting for 83% and 62% of TP during the day and night, respectively. The contribution of DTP to TP in the nightly aerosols samples was much higher than that in the diurnal aerosols. For both day and night samples, inorganic phosphorus was the dominant species of DTP in aerosols, with a ratio of 71%-77%.
RESUMEN
It is widely accepted that the role of the high molecular weight (HMW) component is cooperative in shear-induced crystallization, owing to entanglements among long chains. However, this paper demonstrates that the HMW component has a novel effect on structural evolution during the process of multi-melt multi-injection molding (M3IM), organized as follows. First, the appropriate HDPE system with an incremental concentration of HMW tails was established. Second, the crystalline morphologies and orientation behaviors of the M3IM samples were characterized using a combination of scanning electron microscopy (SEM) and two-dimensional small angle X-ray scattering (2D-SAXS), and these suggested that the amount of shish-kebabs was not monotonically promoted with an increasing content of HMW tails but tended to reduce at a certain value. Third, in order to explain this phenomenon, the special temperature and shear profiles of M3IM were depicted subsequently, and finally the mechanism of hierarchical structure formation with the influence of various amounts of HMW tail chains was discussed, based on the classical rheological viewpoint.
RESUMEN
Size-segregated atmospheric aerosol samples were collected from September 2015 to February 2016 at a coastal site in Qingdao, and the concentrations of major water-soluble inorganic ions were analyzed by ion chromatography. Characteristics and variation of size distribution of secondary inorganic components in aerosol were discussed, as well as the formation process and influencing factors of SNA(sulfate, nitrate and ammonium). The results indicated that the concentrations of NO3-, SO42-, NH4+, NO2-, Cl- in the aerosols were in the range of 10.32-193.46, 4.42-74.05, 2.21-57.75, 0.05-2.22 and 1.35-17.39 µg·m-3 respectively. And the mass concentration of SNA increased with the intensity of haze pollution. The concentrations of NO3- on the slight, mild, moderate and severe haze days were 55%, 77%, 240% and 537% higher than that on non-haze days respectively, while concentrations of SO42- increased by 4.7%, 35%, 77% and 262% respectively, and concentrations of NH4+ increased by 72%, 83%, 201% and 526% respectively. The contribution of these water-soluble ions to PM2.5 showed that the proportion of sum of NO3-, SO42-, NH4+, NO2- and Cl- to PM2.5 was in range of 62.03%-80.93%. The proportion of ion to PM2.5 decreased in the order of NO3- > SO42- > NH4+ > Cl- > NO2-. With the enhancement of haze pollution, the proportion of NO3- in PM2.5 increased from 29.53% to 45.54%. The correlation analysis showed that NO3- and SO42- in the fine particle were significantly correlated with gaseous precursors NO2 and SO2, and also showed good correlations with relative humidity, visibility, wind speed and other weather conditions. These results indicated that the formation of SNA in fine particles was one of the main reasons for visibility decrease and the formation of air pollution in haze days. Meanwhile, high concentration of gaseous precursors, high relative humidity and low wind speed were the important influencing factors of haze formation. Except for slight haze days, SOR and NOR in the haze days were higher than those on the non-haze days, and increased significantly with the intensifying of haze, especially for 0.43-0.65 and 0.65-1.1 µm particle size. Conversion rates of nitrogen and sulfur in severe haze days were 1.5 times that in non-haze days, which showed nitrate and sulfate in these fine mode were mainly from gas-to-particle conversion. NO3-, SO42-, NH4+ and NO2- increased in haze significantly, which mainly existed in the fine particles. The cloud process played a more important role on haze days. While on non-haze day, cloud process and the heterogeneous reaction were both the main factors. And the highest proportion of fine mode concentration to total one was observed for NO3-(79.4%) and SO42-(74.4%) on severe haze days respectively. NO3- showed a bimodal distribution with peaks in the size-bin of 0.43~0.65 µm and 3.3-4.7 µm on non-haze, slight, mild haze days, and the fine peak moved to 0.65-1.1 µm on moderate haze days, however the bimodal distribution changed to unimodal distribution with peak at 0.65-1.1 µm on severe hazy days. SO42- showed a bimodal distribution with peaks at 0.43-0.65 µm and 2.1-3.3 µm in the non-haze weather, while the size distribution changed to unimodal distribution on hazy days. But the peak sizes were different in different intensity of haze, with peak at 0.43-0.65 µm on mild and slight haze and 0.65-1.1 µm in moderate and severe haze days. NH4+ showed a single peak distribution in the fine mode, with the peak in the particle size of 0.43-0.65 µm on slight and non-hazy days, and 0.65-1.1 µm on mild, moderate and severe hazy days. Therefore, haze has a great influence on the size distribution of SNA.
RESUMEN
The formation of a hybrid shish-kebab (HSK) structure with different degrees of lamellar orientations was first observed in the solution crystallization of polyethylene (PE) in the presence of carbon nanofibers (CNFs). In this study, PE crystal lamellae were periodically decorated on the surface of CNFs and were aligned approximately perpendicular to the long axes of the CNFs, forming aligned hybrid shish-kebab nanostructures. More importantly, the fascinating structure was directly formed in all regions of the injection molded bars of HDPE/CNF composites, via a gas-assisted injection molding (GAIM), instead of the shell-core structure. In the GAIM process, an intense shear was imposed onto the melt during the melt second flow and drove PE chains to orient along the axes of the CNFs. Then the entropy penalty for PE chains deposited on the CNF surface was drastically decreased. Although the attractive van der Waals interactions were weak, the oriented PE chains could successfully adsorb on the CNF surface due to the decrease of the entropy penalty, therewith the underlayer coating was formed along the axis based on a two-dimensional mode for early nucleation on the CNF surface. Subsequently, subglobules appeared on the ordered structure, which could be regarded as the crystal nucleus. Finally, the oriented PE chains began to epitaxially grow from the subglobules with a folded-chain shape to decrease the polymer surface energy and grew perpendicular to the CNFs long axis, abiding by the "soft epitaxy" crystallization mechanism regardless of strict lattice matching.
RESUMEN
Graphene quantum dots (GQDs) possess unique properties of graphene and exhibit a series of new phenomena of 0 dimension (D) carbon materials. Thus, GQDs have attracted much attention from researchers and have shown great promise for many applications. Recently, many works focus on GQDs-metal ions and metal nanoparticles (NPs). Although, many researches point out that metal ions and metal NPs have significant effect on photoluminescence (PL) feature of GQDs, mainly focus on PL intensity. Here, for the first time, we reported that metal NPs also affected PL peak position which was dependent on the mix mechanism of metal and GQDs. When GQDs-silver (Ag) composite mixed by physical method and excited at a wavelength of 320 nm, PL peak position of composites first showed blue-shifted then red-shifted with increasing of Ag content. However, if GQDs-Ag composite prepared by chemical method, PL peak position of the composites blue-shifted. Furthermore, the shift of PL peak position of GQDs-Ag prepared both for physical and chemical method displayed excitation-dependent feature. When the excitation wavelength approached to Ag SPR peaks, no obvious PL shift was observed. The mechanism for different PL shifts and the phenomenon of excitation-dependent PL shift as well as the formation mechanism of GQDs-Ag composite by chemical method are discussed in detail in this paper.
RESUMEN
A strong shear flow was imposed on the melt of polycarbonate (PC) microfibrils with ß-nucleation agent reinforced isotactic polypropylene (iPP) during the melt second flow process, i.e. gas-assisted injection molding (GAIM). A special shell-core structure was formed in the iPP/PC microfibrils with ß-nucleation agent (PP/PC/ß-NA) composites. A lot of ß-transcrystalline and α-transcrystalline superstructures were observed in the skin and sub-skin regions, whereas ß-spherulite structures were formed in the gas channel region. There is no doubt that the distinct hierarchical structure has great potential to significantly improve the mechanical performance of the composites, and the experimental results verify this. The results of the mechanical performance testing show that the yield strength of the PP/PC/ß-NA composites reached 61.9 MPa, which is 19.7 MPa higher than that of the iPP parts molded by GAIM (G-iPP) (42.2 MPa). The tensile modulus of the PP/PC/ß-NA composites (3.3 GPa) increased by 135%, compared to that of G-iPP (1.4 GPa). The high content of ß-crystals improved the elongation at break of the composites compared to the iPP/PC microfibril (PP/PC) composites; the elongation at break of the PP/PC/ß-NA composites (13%) is over 3 times greater than that of the PP/PC composites (4%).
RESUMEN
OBJECTIVE: To determine the value of blink reflex in early diagnosis and prognosis evaluation of Bell palsy. METHODS: Blink reflex and facial nerve conduction were examined in 58 patients with Bell palsy within one week after symptom onset. The patients without response of R1 , R2 and R2 ' waves were classified as complete efferent retardarce (Group A, 30 cases), and those with response of R1 , R2 and R2 ' waves were classified as incomplete efferent anomalies (Group B, 28 cases). The clinical outcomes after three months of systemic therapy were evaluated using the House-Blackmann (H-B) scale. RESULTS: Efferent anomalies of blink reflex occurred in ail of the 58 patients. Abnormal results of facial nerve conduction appeared in 23 (39. 7%) patients. The three months therapy was effective in 93% patients in Group B and 70% patients in Group A (P<0. 05). CONCLUSION: Blink reflex can play a significant role in early diagnosis and prognosis evaluation of Bell palsy.
Asunto(s)
Parálisis de Bell/diagnóstico , Parpadeo , Diagnóstico Precoz , Nervio Facial/fisiopatología , Humanos , PronósticoRESUMEN
OBJECTIVE: To explore the profile of false memory in aMCI (amnesia mild cognitive impairment) and to elucidate the neuropsychological mechanism of false memory. METHODS: False memory provoked by pictures and feeling-of-knowing (FOK) test in episodic memory (EM) were conducted in 25 aMCI patients at our hospital from October 2009 to May 2010. And 25 age and education level-matched healthy patients were recruited into the healthy control (HC) group. RESULTS: As compared with HC group, the rate of false memory was higher in the aMCI group. The rate of false memory in recall stage was 26% ± 7% and that of questionnaire stage 28% ± 12%. And the difference between two group was significant (t = 14.437, 7.597, P < 0.05). The FOK-EM of correct judgment and false recognition in the aMCI group (41% ± 10%) was higher than the HC group. And the difference was significant (t = 4.207, P < 0.05). The rates of false memory in recall and questionnaire stages were positively correlated with FOK-EM in aMCI group (r = 0.563, 0.705, P < 0.01). CONCLUSION: The aMCI patients tend to have more false memory provoked by pictures. The deficit of memory monitoring in aMCI may be the foundation of false memory.