RESUMEN
Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM's broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM's molecular mechanisms and offer potential targets for improving treatment efficacy.
Asunto(s)
Desoxicitidina , Gemcitabina , Proteómica , Proteínas Quinasas Asociadas a Fase-S , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Humanos , Proteómica/métodos , Línea Celular Tumoral , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Proteínas Quinasas Asociadas a Fase-S/genética , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Regulación hacia Arriba/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Second-harmonic-generation (SHG) switching is an emerging phenomenon with potential applications in bistable storage and optical switches while also serving as a sensitive probe for inversion-symmetry. Temperature-induced disorder-order phase transition has been proven to be a rational design strategy for achieving SHG bi-state switching; however, pressure-sensitive SHG switching via a disorder-order structural transition mechanism is rarely reported and lacks sensitivity and cyclicity as practical switching materials. Herein, we demonstrate the pressure-induced "dynamical disorder-order" phase transition as an effective strategy for triggering SHG and SHG switching in NH4Cl. The "dynamical disorder-order" phase transition of NH4Cl occurring at as low as 1 GPa is confirmed by comprehensive in situ high-pressure XRD, molecular vibrational spectra, and Brillouin scattering spectra. The pressure-induced SHG is responsive to a wide excitation wavelength region (800-1500 nm), and the "off-on" switching is reversible for up to 50 cycles, setting a record for pressure-driven switching materials. It is worth noting that when pressure is further increased to 14 GPa, NH4Cl exhibits another SHG "on-off" switching, which makes it the first triplet SHG "off-on-off" switching material. Molecular dynamics simulations reveal the key role of N-H···Cl hydrogen bonding in the pressure-induced "dynamic disorder-order" mechanism. Finally, we verified that chemical pressure and physical pressure can jointly regulate the SHG switching behavior of NH4X (X = Cl, Br). The pressure-driven "dynamic disorder-order" transition mechanism sheds light on the rational design of multistable SHG switching materials for photoswitches and information storage.
RESUMEN
Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.
RESUMEN
BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.
Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Hiperglucemia , Humanos , Femenino , Anciano , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios Retrospectivos , Glucemia/análisis , Factores de RiesgoRESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.
Asunto(s)
Biomarcadores , Glucemia , Enfermedades Cardiovasculares , Causas de Muerte , Diabetes Mellitus , Resistencia a la Insulina , Encuestas Nutricionales , Triglicéridos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Glucemia/metabolismo , Medición de Riesgo , Triglicéridos/sangre , Biomarcadores/sangre , Estudios Transversales , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus/mortalidad , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Factores de Tiempo , Pronóstico , Anciano , Adulto , Estados Unidos/epidemiología , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
KEY MESSAGE: The rust resistance genes Lr53 and Yr35 were introgressed into bread wheat from Aegilops longissima or Aegilops sharonensis or their S-genome containing species and mapped to the telomeric region of chromosome arm 6BS. Wheat leaf and stripe rusts are damaging fungal diseases of wheat worldwide. Breeding for resistance is a sustainable approach to control these two foliar diseases. In this study, we used SNP analysis, sequence comparisons, and cytogenetic assays to determine that the chromosomal segment carrying Lr53 and Yr35 was originated from Ae.longissima or Ae. sharonensis or their derived species. In seedling tests, Lr53 conferred strong resistance against all five Chinese Pt races tested, and Yr35 showed effectiveness against Pst race CYR34 but susceptibility to race CYR32. Using a large population (3892 recombinant gametes) derived from plants homozygous for the ph1b mutation obtained from the cross 98M71 × CSph1b, both Lr53 and Yr35 were successfully mapped to a 6.03-Mb telomeric region of chromosome arm 6BS in the Chinese Spring reference genome v1.1. Co-segregation between Lr53 and Yr35 was observed within this large mapping population. Within the candidate region, several nucleotide-binding leucine-rich repeat genes and protein kinases were identified as candidate genes. Marker pku6B3127 was completely linked to both genes and accurately predicted the absence or presence of alien segment harboring Lr53 and Yr35 in 87 tetraploid and 149 hexaploid wheat genotypes tested. We developed a line with a smaller alien segment (< 6.03 Mb) to reduce any potential linkage drag and demonstrated that it conferred resistance levels similar to those of the original donor parent 98M71. The newly developed introgression line and closely linked PCR markers will accelerate the deployment of Lr53 and Yr35 in wheat breeding programs.
Asunto(s)
Aegilops , Mapeo Cromosómico , Resistencia a la Enfermedad , Genes de Plantas , Puccinia , Aegilops/genética , Aegilops/microbiología , Cromosomas de las Plantas/genética , Resistencia a la Enfermedad/genética , Introgresión Genética , Ligamiento Genético , Marcadores Genéticos , Fitomejoramiento , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Polimorfismo de Nucleótido Simple , Puccinia/fisiología , Triticum/genética , Triticum/microbiologíaRESUMEN
Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO2 nanosheets to Mn2+, resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL-1. In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.
Asunto(s)
Técnicas Biosensibles , Plaguicidas , Plaguicidas/análisis , Compuestos Organofosforados , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Sistemas CRISPR-Cas , Diclorvos , Agua , Compuestos de Manganeso , Óxidos , Acetilcolina , Técnicas Biosensibles/métodosRESUMEN
To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.
Asunto(s)
Atractylodes , Atractylodes/química , Hidroquinonas , Antiinflamatorios , Dicroismo Circular , Estructura MolecularRESUMEN
Three new strains of dissimilatory perchlorate-reducing bacteria (DPRB), QD19-16, QD1-5, and P3-1, were isolated from an active sludge. Phylogenetic trees based on 16S rRNA genes indicated that QD19-16, QD1-5, and P3-1 belonged to Brucella, Acidovorax, and Citrobacter, respectively, expanding the distribution of DPRB in the Proteobacteria. The three strains were gram-negative and facultative anaerobes with rod-shaped cells without flagella, which were 1.0-1.6 µm long and 0.5-0.6 µm wide. The three DPRB strains utilized similar broad spectrum of electron donors and acceptors and demonstrated a similar capability to reduce perchlorate within 6 days. The enzyme activity of perchlorate reductase in QD19-16 toward chlorate was higher than that toward perchlorate. The high sequence similarity of the perchlorate reductase operon and chlorite dismutase genes in the perchlorate reduction genomic islands (PRI) of the three strains implied that they were monophyletic origin from a common ancestral PRI. Two transposase genes (tnp1 and tnp2) were found in the PRIs of strain QD19-16 and QD1-5, but were absent in the strain P3-1 PRI. The presence of fragments of IR sequences in the P3-1 PRI suggested that P3-1 PRI had previously contained these two tnp genes. Therefore, it is plausible to suggest that a common ancestral PRI transferred across the strains Brucella sp. QD19-16, Acidovorax sp. QD1-5, and Citrobacter sp. P3-1 through horizontal gene transfer, facilitated by transposases. These results provided a direct evidence of horizontal gene transfer of PRI that could jump across phylogenetically unrelated bacteria through transposase. KEY POINTS: ⢠Three new DPRB strains can effectively remove high concentration of perchlorate. ⢠The PRIs of three DPRB strains are acquired from a single ancestral PRI. ⢠PRIs are incorporated into different bacteria genome through HGT by transposase.
Asunto(s)
Islas Genómicas , Percloratos , Filogenia , Oxidación-Reducción , Transferencia de Gen Horizontal , ARN Ribosómico 16S/genética , Bacterias/genética , Oxidorreductasas/genética , Ecosistema , Transposasas/genéticaRESUMEN
The optical surface of extreme ultraviolet (EUV) lithography machines is highly vulnerable to contamination by hydrocarbons, resulting in the formation of carbon deposits that significantly degrade the quality and efficiency of lithography. The dynamic gas lock (DGL) has been proven as an effective approach to alleviate carbon deposition. However, the majority of existing studies on carbon deposition neglect the influence of the DGL. This paper is dedicated to investigating the phenomena of hydrocarbon adsorption, desorption, and cleavage with considering the effects of the DGL. A comprehensive mathematical model of the carbon deposition process is established, and the impact of radiation intensity, temperature, and hydrocarbon types on the depositing rate is considered. The results suggest that the primary cause of carbon deposition is the direct cracking of hydrocarbons induced by photons with a wavelength range between 12.5 and 14.5 nm. Additionally, it has been observed that the carbon deposition rate decreases exponentially as clean gas flow increases when EUV radiation intensity exceeds 50 mW/mm2. Conversely, at low EUV radiation intensity, clean gas flow has little effect on the carbon deposition rate. An effective approach to mitigate carbon deposition is to elevate the temperature of the optical surface and employ light hydrocarbon materials in the EUV process.
RESUMEN
AIM: To investigate the DNA damage response (DDR) in a cyclophosphamide (CTX)-induced mouse model of premature ovarian failure (POF). METHODS: The POF model was established by injecting mice with CTX. The body, ovarian weights, the estrus cycle, and pathological changes of the ovaries were recorded. The serum levels of 17 ß-estradiol (E2) and follicle-stimulating hormone (FSH) were measured. The expression of Ki67, ß-galactosidase (ß-gal), p21, p53, γH2AX, and pATM in ovarian tissues was detected by immunohistochemistry. The expression of ß-gal, γH2AX, and pATM was analyzed by immunofluorescence staining of primary cultured granulosa cells (GCs). RESULTS: The body and ovarian weights decreased, the estrus cycles were erratic, and the FSH level increased, whereas the E2 level decreased in POF mice compared to controls. The pathological consequences of POF revealed an increase in atretic follicles, corpus luteum, and primordial follicles and a decrease in the number of primary, secondary, and tertiary follicles. Ki67 expression was reduced, ß-gal, p21, p53, γH2AX, and pATM expression were elevated in the ovaries of POF mice. The expression of ß-gal, γH2AX, and pATM increased in GCs with the concentration in a time-dependent manner. CONCLUSION: In total, CTX induced POF in mice, which was mediated by the DDR pathway of ATM-P53-P21.
RESUMEN
Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat. Cultivated einkorn (Triticum monococcum L. ssp. monococcum, 2n = 2x = 14, AmAm), one of the founder crops of agriculture, harbors unexploited genetic sources for wheat improvement. An advanced wheat line, Z15-1949, with 42 chromosomes, selected from the hybrids of Pst-susceptible common wheat cultivar Crocus and resistant T. monococcum accession 10-1, exhibits high resistance to a mixture of the prevalent Chinese Pst races. Genetic analysis on F1, F2, and F2:3 generations of the cross between Z15-1949 and Pst-susceptible common wheat SY95-71 indicated that the resistance of Z15-1949 was conferred by a recessive gene, tentatively designated as YrZ15-1949. This gene was mapped to the short arm of chromosome 7D using the Wheat 55K single nucleotide polymorphism array, flanked by markers KASP-1949-2 and KASP-1949-10 within a 3.3-cM genetic interval corresponding to a 1.12-Mb physical region in the Chinese Spring reference genome V2.0. The gene differs from previously reported Yr genes on 7D based on their physical positions and is probably a novel gene. YrZ15-1949 would be a valuable resource for developing Pst-resistant wheat cultivars, and the linked markers could be used for marker-assisted selection.
Asunto(s)
Basidiomycota , Mapeo Cromosómico , Resistencia a la Enfermedad , Enfermedades de las Plantas , Puccinia , Triticum , Triticum/microbiología , Triticum/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Resistencia a la Enfermedad/genética , Basidiomycota/fisiología , Basidiomycota/genética , Genes Recesivos , Cromosomas de las Plantas/genética , Genes de Plantas/genética , Polimorfismo de Nucleótido Simple/genética , Marcadores Genéticos/genéticaRESUMEN
BACKGROUND: There is an increasing number of different brands of robotic total knee arthroplasty (TKA) systems. Most robotic TKA systems share the same coronal alignment, while the definitions of sagittal alignment vary. The purpose of this study was to investigate whether these discrepancies impact the sagittal alignment of the lower extremity. METHODS: A total of 72 lower extremity computed tomography scans were included in our study, and 3-dimensional models were obtained using software. A total of 7 brands of robotic TKA systems were included in the study. The lower extremity axes were defined based on the surgical guide for each implant. We also set the intramedullary axis as a reference to evaluate the discrepancies in sagittal alignment of each brand of robotic system. RESULTS: On the femoral side, the axis definition was the same for all 7 robotic TKA systems. The robotic TKA axes showed a 2.41° (1.58°, 3.38°) deviation from the intramedullary axis. On the tibial side, the 7 robots had different axis definitions. The tibial mechanical axis of 6 of the TKA systems was more flexed than that of the intramedullary axis, which means the posterior tibial slope was decreased while the tibial mechanical axis of the remaining system was more extended. CONCLUSIONS: The sagittal alignment of the lower extremity for 7 different brands of robotic TKA systems differed from each other and all deviated from the intramedullary axis. Surgeons should be aware of this discrepancy when using different brands of robotic TKA systems to avoid unexpected sagittal alignment and corresponding adverse clinical outcomes. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Procedimientos Quirúrgicos Robotizados , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Masculino , Femenino , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Prótesis de la Rodilla , Tibia/cirugía , Tibia/diagnóstico por imagen , Anciano , Extremidad Inferior/cirugía , Extremidad Inferior/diagnóstico por imagen , Fémur/cirugía , Fémur/diagnóstico por imagen , Persona de Mediana Edad , Imagenología TridimensionalRESUMEN
PURPOSE: Robot-assisted total hip arthroplasty (RA-THA) helps with precise orientation of the prosthesis, but some RA-THA procedures are aborted intraoperatively and are converted to manual total hip arthroplasty (THA). This study aimed to analyse why RA-THA is sometimes aborted intraoperatively and to make recommendations accordingly. METHODS: A total of 429 consecutive Mako THA cases in our prospective database from August 2018 to June 2021 were included in our study. All robotic procedures aborted intraoperatively for any reason were recorded. The patients' demographics, diagnoses, and surgeons' information were included in the statistical analysis to pinpoint the risk factors for intraoperative robot to manual conversion. RESULTS: Intraoperative RA-THA abortions occurred in 17 cases (3.96%) and the patients had to be converted to manual THA. The adverse events leading to intraoperative abortions included pelvic array loosening or malposition (5, 1.17%), inaccurate bone mapping or construction (6, 1.40%), inaccurate initial registration (4, 0.93%), and other reasons (2, 0.47%). CONCLUSION: Robot-related adverse events could be found in all perioperative steps of RA-THA, and some of these events might result in intraoperative abortion. Complex hip disease was a statistically significant factor for an increased risk of intraoperative abortion of RA-THA. Standardized surgical procedures and preoperative assessments can be helpful in reducing the rate of RA-THA abortions.
RESUMEN
Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV). HIV protease, reverse transcriptase, and integrase are targets of current drugs to treat the disease. However, anti-viral drug-resistant strains have emerged quickly due to the high mutation rate of the virus, leading to the demand for the development of new drugs. One attractive target is Gag-Pol polyprotein, which plays a key role in the life cycle of HIV. Recently, we found that a combination of M50I and V151I mutations in HIV-1 integrase can suppress virus release and inhibit the initiation of Gag-Pol autoprocessing and maturation without interfering with the dimerization of Gag-Pol. Additional mutations in integrase or RNase H domain in reverse transcriptase can compensate for the defect. However, the molecular mechanism is unknown. There is no tertiary structure of the full-length HIV-1 Pol protein available for further study. Therefore, we developed a workflow to predict the tertiary structure of HIV-1 NL4.3 Pol polyprotein. The modeled structure has comparable quality compared with the recently published partial HIV-1 Pol structure (PDB ID: 7SJX). Our HIV-1 NL4.3 Pol dimer model is the first full-length Pol tertiary structure. It can provide a structural platform for studying the autoprocessing mechanism of HIV-1 Pol and for developing new potent drugs. Moreover, the workflow can be used to predict other large protein structures that cannot be resolved via conventional experimental methods.
Asunto(s)
Infecciones por VIH , VIH-1 , Productos del Gen pol del Virus de la Inmunodeficiencia Humana , Humanos , Productos del Gen pol/genética , Productos del Gen pol/metabolismo , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/genética , Proteasa del VIH/metabolismo , VIH-1/genética , VIH-1/metabolismo , Poliproteínas/genética , ADN Polimerasa Dirigida por ARN/metabolismo , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/químicaRESUMEN
Leaf rolling is regarded as an important morphological trait in wheat breeding. Moderate leaf rolling is helpful to keep leaves upright and improve the photosynthesis of plants, leading to increased yield. However, studies on the identification of genomic regions/genes associated with rolling leaf have been reported less frequently in wheat. In this study, a rolling leaf mutant, T73, which has paired spikelets, dwarfism, and delayed heading traits, was obtained from a common wheat landrace through ethyl methanesulfonate mutagenesis. The rlT73 mutation caused an increase in the number of epidermal cells on the abaxial side and the shrinkage of bulliform cells on the adaxial side, leading to an adaxially rolling leaf phenotype. Genetic analysis showed that the rolling leaf phenotype was controlled by a single recessive gene. Further Wheat55K single nucleotide polymorphism array-based bulked segregant analysis and molecular marker mapping delimited rlT73 to a physical interval of 300.29-318.33 Mb on the chromosome arm 1BL in the Chinese Spring genome. We show that a point mutation at the miRNA165/166 binding site of the HD zipper class III transcription factor on 1BL altered its transcriptional level, which may be responsible for the rolling leaf phenotype. Our results suggest the important role of rlT73 in regulating wheat leaf development and the potential of miRNA-based gene regulation for crop trait improvement.
Asunto(s)
Fitomejoramiento , Triticum , Alelos , Triticum/genética , Mutación , CromosomasRESUMEN
The priming effect stands as a critical factor influencing the balance of soil organic carbon (SOC). Following vegetation restoration, the carbon (C) pool stability in Platycladus orientalis forests (PO) varies, and the priming effect resulting from exogenous C addition also differs significantly. Here, we selected PO with restoration ages of 10, 15, and 30 years in the rocky mountainous area in northern China and conducted measurements of soil properties, microbial communities, microbial necromass C (MNC), SOC fractions, and the priming effect characteristics to explore the main influencing factors of the priming effect, especially the microbiological mechanisms. Our results showed that the ratio of mineral-associated organic C to particulate organic C increased. The characteristics of the priming effect showed the same pattern, and there was a significant positive correlation between the C pool stability and the priming effect. The diversity of the fungal communities increased with increasing vegetation restoration age, and the content and proportion of fungal necromass C (FNC) also increased synchronously, reaching the maximum value in the soil of PO that had been restored for 30 years. In addition, the soil water content and total nitrogen indirectly affected the priming effect by influencing the microbial communities. In summary, the results suggested that vegetation restoration can enhance the C pool stability by promoting an increase in soil FNC, thereby producing a positive priming effect. This can help deepen our understanding of the SOC mineralization changes induced by fresh C input following vegetation restoration and provides a theoretical basis for better explaining the C cycle between soil and atmosphere under the vegetation restoration models in the future.
Asunto(s)
Carbono , Suelo , Carbono/análisis , Microbiología del Suelo , Bosques , China , MineralesRESUMEN
OBJECTIVES: To identify the patterns and influencing factors of oral health service utilization among college students, and further to provide scientific evidence for policy making on oral health education and behavioral interventions for the college population. METHODS: The study population was college students in Southern China. Totally 678 students participated in the survey. A self-designed questionnaire based on Anderson's model (predisposing factors, enabling factors, need factors) was used to survey college students. Descriptive statistics, χ2 test, and logistic regression were used to analyze influence factors of oral health service utilization among college students. RESULTS: The utilization rate of oral health service in the past 12 months was 30.2%. The primary type of oral health service was treatment (59.6%), and only 12.8% were for prevention. There were 39% of the participants having oral health diseases, of which dental caries (25.7%) and oral bleeding (22.2%) were the main problems. The results from logistic regression analysis revealed that students with better beliefs (OR = 1.84, 95% CI:=1.02-3.43), frequent consumption of sugary drinks (OR = 2.90, 95% CI:=1.90-4.47), teeth brushing frequency > = 2 times per day (OR = 2.09, 95% CI = 1.24-3.61), frequent floss utilization (OR = 2.63, 95% CI = 1.21-5.76), dental caries (OR = 2.07, 95% CI = 1.35-3.17) used oral health services higher, while those lived in rural areas (OR:0.52, 95% CI = 0.34-0.80), and had only a fair concern (OR = 0.48, 95% CI = 0.31-0.74) or no concern (OR = 0.26, 95% CI = 0.08-0.67) on oral health utilized oral health services lower. CONCLUSIONS: Chinese college students demonstrate some knowledge and attitudes towards oral health. However, they tend to neglect oral hygiene and have limited understanding of their own oral issues. Furthermore, the utilization of oral services, such as treatment, remains remarkably low, despite the availability of long-term and favorable health insurance policies. The utilization of oral health services among college students is influenced by various factors, including residing in rural areas, consuming sugary beverages on a daily basis, brushing teeth at least twice a day, and practicing flossing.
Asunto(s)
Caries Dental , Servicios de Salud Dental , Humanos , Adolescente , Caries Dental/epidemiología , Caries Dental/prevención & control , Salud Bucal , Higiene Bucal , ChinaRESUMEN
Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.
Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Control de Calidad , Humanos , Biomarcadores/análisisRESUMEN
Numerous studies have shown a fact that phase transformation and/or reconstruction are likely to occur and play crucial roles in electrochemical scenarios. Nevertheless, a decisive factor behind the diverse photoelectrochemical activity and selectivity of various copper/silicon photoelectrodes is still largely debated and missing in the community, especially the possibly dynamic behaviors of metal catalyst/semiconductor interface. Herein, through in situ X-ray absorption spectroscopy and transmission electron microscope, a model system of Cu nanocrystals with well-defined facets on black p-type silicon (BSi) is unprecedentedly demonstrated to reveal the dynamic phase transformation of forming irreversible silicide at Cu nanocrystal-BSi interface during photoelectrocatalysis, which is validated to originate from the atomic interdiffusion between Cu and Si driven by light-induced dynamic activation process. Significantly, the adaptive junction at Cu-Si interface is activated by an expansion of interatomic Cu-Cu distance for CO2 electroreduction, which efficiently restricts the C-C coupling pathway but strengthens the bonding with key intermediate of *CHO for CH4 yield, resulting in a remarkable 16-fold improvement in the product ratio of CH4/C2 products and an intriguing selectivity switch. This work offers new insights into dynamic structural transformations of metal/semiconductor junction and design of highly efficient catalysts toward photosynthesis.