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1.
Front Immunol ; 15: 1445239, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39295873

RESUMEN

Introduction: In the course of immune development, HIV-exposed uninfected (HEU) infants exhibit abnormal immune function and increased infectious morbidity compared to HIV-unexposed uninfected (HUU) infants. Yet the specific functional phenotypes and regulatory mechanisms associated with in-utero HIV and/or ART exposure remain largely obscure. Methods: We utilized flow cytometry and RNA-seq technologies to conduct the immunological and transcriptomic profiling in cord blood from 9 HEU mother-infant pairs and 24 HUU pairs. On top of that, we compared the cord blood dataset with the maternal venous blood dataset to characterize unique effects induced by in-utero HIV and/or ART exposure. Results: Flow cytometry immunophenotyping revealed that the level of B lymphocyte subsets was significantly decreased in HEU cord blood as compared to HUU (P < 0.001). Expression profiling-based cell abundance assessment, includes CIBERSORT and ssGSEA algorithm, showed a significantly reduced abundance of naive B cells in HEU cord blood (both P < 0.05), supporting the altered composition of B lymphocyte subsets in HEU. Functional enrichment analysis demonstrated suppressed innate immune responses and impaired immune regulatory function of B cells in HEU cord blood. Furthermore, through differential expression analysis, co-expression network analysis using WGCNA, and feature selection analysis using LASSO, we identified a 4-gene signature associated with HEU status. This signature effectively assesses B cell levels in cord blood, enabling discrimination between HEU and HUU infants. Discussion: Our study provides the first comprehensive immunological and transcriptomic characterization of HEU cord blood. Additionally, we establish a 4-gene-based classifier that holds potential for predict immunological abnormalities in HEU infants.


Asunto(s)
Sangre Fetal , Perfilación de la Expresión Génica , Infecciones por VIH , Transcriptoma , Humanos , Sangre Fetal/inmunología , Femenino , Infecciones por VIH/inmunología , Embarazo , Recién Nacido , Lactante , Masculino , Linfocitos B/inmunología , Subgrupos de Linfocitos B/inmunología , Inmunofenotipificación , Adulto , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/sangre , Transmisión Vertical de Enfermedad Infecciosa
2.
J Colloid Interface Sci ; 678(Pt C): 120-133, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39288573

RESUMEN

In this paper, a 2 dimensional (2D) metal-organic frameworks (MOFs) nanosheets grown on 1D ZIF-67 modified carbon nanofibers (CNFs) was designed and fabricated with a hierarchical heterostructure. The hierarchical 2D/1D MOFs/CCNF offers rich electrochemical active sites and favorable ion/electron diffusion pathways. The synergistic effect of Co, CNFs and MOFs from heterostructures contributes to superb electrochemical activities. Benefiting from the hierarchical heterostructures optimized by the mass ratio of ZIF-67/PAN and CCNF/NiMOF as well as the type of substrates, CCNF-20@MOF showed a specific capacity of 361.50 C g-1 at 0.5 A g-1, whose charge storage mechanism is dominated by diffusion control. Meanwhile, a bamboo-derived carbon material (BBC) was designed in the solid-state asymmetric supercapacitor (CCNF-20@MOF//BBC). The device exhibited an energy density of 38.89 Wh kg-1 at the power density of 800.02 W kg-1 and excellent cycling stability, that exceed many MOFs based devices. Moreover, it could be successfully used for LED light-emitting, demonstrating a good application prospect. This work provides a feasible strategy for the improved performance of MOFs and CNFs based materials in the field of energy storage.

3.
Environ Res ; : 120025, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293756

RESUMEN

Neonicotinoids (NEOs), despite their widespread use as insecticides, exhibit a notable knowledge deficit in regards to their presence in wastewater treatment plants (WWTPs) and their surrounding environments. This study delves into the presence and disposition of 5 NEOs: Thiamethoxam (THM), Clothianidin (CLO), Imidacloprid (IMD), Acetamiprid (ACE), and Thiacloprid (THA) across 3 domestic WWTPs and their receiving waters. Notably, THM, CLO, and ACE were consistently detected in all water and sludge samples, with THM emerging as the most abundant compound in both influent and effluent. Among the 3 WWTPs, WWTP 2, employing a fine bubble oxidation process, achieved the highest removal efficiency, surpassing 68%, in contrast to WWTP 1 (CAST) at 37% and WWTP 3 (A/A/O) at 7%. Biodegradation played a pivotal role in NEO removal, accounting for 36.7% and 68.2% of the total removal in WWTP 1 and WWTP 2, respectively. Surprisingly, in WWTP 3, biotransformation process inadvertently increased ACE and CLO concentrations by approximately 4.1% and 4.5%, respectively. The total NEO concentration in the receiving surface waters ranged from 72.7 to 155.5 ng/L, while sediment concentrations were significantly lower, spanning between 0.10 and 1.53 ng/g. WWTPs serve as both a removal and concentration point for NEOs, thereby significantly influencing their transportation. Additionally, the concentration of most NEOs in the receiving waters progressively increased from upstream to downstream, highlighting the substantial impact of WWTP discharges on natural water environments. This research offers valuable insights into NEO pollution surrounding WWTPs in the Pearl River Delta, ultimately aiding in pollution control and environmental protection decisions.

4.
Int J Immunopathol Pharmacol ; 38: 3946320241271724, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39116410

RESUMEN

This study aimed to investigate whether the beneficial effects of PCA on chondrocyte senescence are mediated through the regulation of mitophagy. Chondrocyte senescence plays a significant role in the development and progression of knee osteoarthritis (OA). The compound protocatechuic aldehyde (PCA), which is abundant in the roots of Salvia miltiorrhiza, has been reported to have antioxidant properties and the ability to protect against cellular senescence. To achieve this goal, a destabilization of the medial meniscus (DMM)-induced mouse OA model and a lipopolysaccharide (LPS)-induced chondrocyte senescence model were used, in combination with PINK1 gene knockdown or overexpression. After treatment with PCA, cellular senescence was assessed using Senescence-Associated ß-Galactosidase (SA-ß-Gal) staining, DNA damage was evaluated using Hosphorylation of the Ser-139 (γH2AX) staining, reactive oxygen species (ROS) levels were measured using Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, mitochondrial membrane potential was determined using a 5,5',6,6'-TETRACHLORO-1,1',3,3'-*. TETRAETHYBENZIMIDA (JC-1) kit, and mitochondrial autophagy was examined using Mitophagy staining. Western blot analysis was also performed to detect changes in senescence-related proteins, PINK1/Parkin pathway proteins, and mitophagy-related proteins. Our results demonstrated that PCA effectively reduced chondrocyte senescence, increased the mitochondrial membrane potential, facilitated mitochondrial autophagy, and upregulated the PINK1/Parkin pathway. Furthermore, silencing PINK1 weakened the protective effects of PCA, whereas PINK1 overexpression enhanced the effects of PCA on LPS-induced chondrocytes. PCA attenuates chondrocyte senescence by regulating PINK1/Parkin-mediated mitochondrial autophagy, ultimately reducing cartilage degeneration.


Asunto(s)
Benzaldehídos , Catecoles , Senescencia Celular , Condrocitos , Mitofagia , Proteínas Quinasas , Ubiquitina-Proteína Ligasas , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/patología , Animales , Senescencia Celular/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Mitofagia/efectos de los fármacos , Proteínas Quinasas/metabolismo , Ratones , Catecoles/farmacología , Benzaldehídos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Masculino , Ratones Endogámicos C57BL , Autofagia/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/tratamiento farmacológico
5.
Foods ; 13(16)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39200522

RESUMEN

To further develop Liupao tea products and enhance their flavor, this study investigated the effects of different fermentation methods on the aroma quality of Liupao tea. The aroma quality of Liupao tea was comprehensively analyzed using HS-SPME in combination with GC-Q-TOF-MS, electronic nose, and sensory evaluations. Electronic nose detection showed that the aroma fingerprints of Liupao tea samples with different fermentation methods were different. Sulfides, alcohols, ketones, and methyls were the main aroma categories affecting the aroma of the four groups of Liupao tea samples. GC-Q-TOF-MS analysis revealed significant differences in the composition of aroma components among the four fermentation methods of Liupao tea (p < 0.05). Furthermore, the total amount of aroma compounds was found to be highest in the group subjected to hot fermentation combined with the inoculation of Monascus purpureus (DMl group). Based on the OPLS-DA model, candidate differential aroma components with VIP > 1 were identified, and characteristic aroma compounds were selected based on OAV > 10. The key characteristic aroma compounds shared by the four groups of samples were 1,2,3-Trimethoxybenzene with a stale aroma and nonanal with floral and fruity aromas. The best sensory evaluation results were obtained for the DMl group, and its key characteristic aroma compounds mainly included 1,2,3-Trimethoxybenzene, nonanal, and cedrol. The results of this study can guide the development of Liupao tea products and process optimization.

6.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39105598

RESUMEN

We briefly describe the design of a handheld metal detection instrument based on microjoule high repetition frequency laser-induced breakdown spectroscopy. The instrument uses a Raspberry Pi as the control core and a laser with a frequency of 10 kHz and a single pulse energy of 100 µJ as the excitation source. In addition, a mini-putter is built into the instrument to move the laser, allowing the ablation of the sample surface line area without external auxiliary equipment. The excitation-generated plasma radiation is collected by a simple optical path and transmitted directly to the spectrometer. We also constructed and trained a Backpropagation Artificial Neural Network (BP-ANN) model based on 12 different grades of alloys and transplanted the feedback process of the BP-ANN to the Raspberry Pi, which realized the rapid classification of the 12 alloys with >95% classification accuracy on the handheld instrument.

7.
Plant Cell ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133577

RESUMEN

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found two SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of four near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resultinged in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

8.
Environ Pollut ; 360: 124615, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39059700

RESUMEN

Atmospheric fine particulate matter (PM2.5) can trigger the production of cytotoxic reactive oxygen species (ROS), which can trigger or exacerbate oxidative stress and pulmonary inflammation. We collected 111 daily (∼24 h) ambient PM2.5 samples within an urban region of North China during four seasons of 2019-2020. PM2.5 samples were examined for carbonaceous components, water-soluble ions, and elements, together with their oxidative potential (represent ROS-producing ability) by DTT assay. The seasonal peak DTTv was recorded in winter (2.86 ± 1.26 nmol min-1 m-3), whereas the DTTm was the highest in summer (40.6 ± 8.7 pmol min-1 µg-1). WSOC displayed the highest correlation with DTT activity (r = 0.84, p < 0.0001), but the influence of WSOC on the elevation of DTTv was extremely negligible. Combustion source exhibited the most significant and robust correlation with the elevation of DTTv according to the linear mixed-effects model result. Source identification investigation using positive matrix factorization displayed that combustion source (36.2%), traffic source (30.7%), secondary aerosol (15.7%), and dust (14.1%) were driving the DTTv, which were similar to the results from the multiple linear regression (MLR) analysis. Backward trajectory analysis revealed that the major air masses originate from local and regional transportation, but PM2.5 OP was more susceptible to the influence of short-distance transport clusters. Discerning the influence of chemicals on health-pertinent attributes of PM2.5, such as OP, could facilitate a deep understanding of the cause-and-effect relationship between PM2.5 and impacts.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Monitoreo del Ambiente , Material Particulado , Material Particulado/análisis , China , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Contaminación del Aire/estadística & datos numéricos , Oxidación-Reducción , Estaciones del Año , Especies Reactivas de Oxígeno , Estrés Oxidativo
9.
Commun Biol ; 7(1): 848, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992164

RESUMEN

Filamentous fungi produce polysaccharide-degrading enzymes, which is controlled by poorly understood transcriptional circuits. Here we show that a circuit comprising RsrC-RsrA-RsrB (Rsr: production of raw-starch-degrading enzyme regulator) that positively regulates production of raw starch-degrading enzymes in Penicillium oxalicum. Transcription factor (TF) RsrA is essential for biosynthesis of raw starch-degrading enzymes. RsrB and RsrC containing Zn2Cys6- and C2H2-zinc finger domains, act downstream and upstream of RsrA, respectively. RsrA activates rsrB transcription, and three nucleotides (G-286, G-287 and G-292) of rsrB promoter region are required for RsrA, in terms of TF, for binding. RsrB165-271 binds to DNA sequence 5'-TCGATCAGGCACGCC-3' in the promoter region of the gene encoding key raw-starch-degrading enzyme PoxGA15A. RsrC specifically binds rsrA promoter, but not amylase genes, to positively regulate the expression of rsrA and the production of raw starch-degrading enzymes. These findings expand complex regulatory network of fungal raw starch-degrading enzyme biosynthesis.


Asunto(s)
Proteínas Fúngicas , Regulación Fúngica de la Expresión Génica , Penicillium , Factores de Transcripción , Penicillium/genética , Penicillium/metabolismo , Penicillium/enzimología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regiones Promotoras Genéticas , Polisacáridos/metabolismo , Polisacáridos/biosíntesis , Redes Reguladoras de Genes
10.
Nat Food ; 5(8): 648-649, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39080424
11.
J Med Virol ; 96(6): e29753, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38895800

RESUMEN

Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.


Asunto(s)
Genotipo , Infecciones por Papillomavirus , Infección Persistente , Polimorfismo Genético , Carga Viral , Humanos , Infecciones por Papillomavirus/virología , Femenino , Infección Persistente/virología , Cuello del Útero/virología , Cuello del Útero/patología , Adulto , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Frecuencia de los Genes , Proteínas Oncogénicas Virales/genética , Virulencia/genética , Alphapapillomavirus/genética , Alphapapillomavirus/patogenicidad , Alphapapillomavirus/clasificación , Alphapapillomavirus/aislamiento & purificación , Virus del Papiloma Humano
12.
Nat Commun ; 15(1): 5346, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914561

RESUMEN

Global patterns of leaf nitrogen (N) and phosphorus (P) stoichiometry have been interpreted as reflecting phenotypic plasticity in response to the environment, or as an overriding effect of the distribution of species growing in their biogeochemical niches. Here, we balance these contrasting views. We compile a global dataset of 36,413 paired observations of leaf N and P concentrations, taxonomy and 45 environmental covariates, covering 7,549 sites and 3,700 species, to investigate how species identity and environmental variables control variations in mass-based leaf N and P concentrations, and the N:P ratio. We find within-species variation contributes around half of the total variation, with 29%, 31%, and 22% of leaf N, P, and N:P variation, respectively, explained by environmental variables. Within-species plasticity along environmental gradients varies across species and is highest for leaf N:P and lowest for leaf N. We identified effects of environmental variables on within-species variation using random forest models, whereas effects were largely missed by widely used linear mixed-effect models. Our analysis demonstrates a substantial influence of the environment in driving plastic responses of leaf N, P, and N:P within species, which challenges reports of a fixed biogeochemical niche and the overriding importance of species distributions in shaping global patterns of leaf N and P.


Asunto(s)
Nitrógeno , Fósforo , Filogenia , Hojas de la Planta , Fósforo/metabolismo , Hojas de la Planta/metabolismo , Nitrógeno/metabolismo , Ecosistema , Plantas/metabolismo , Plantas/clasificación , Ambiente , Especificidad de la Especie
13.
Hortic Res ; 11(6): uhae110, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38898960

RESUMEN

Flowers and fruits are the reproductive organs in plants and play essential roles in natural beauty and the human diet. CLAVATA (CLV) signaling has been well characterized as regulating floral organ development by modulating shoot apical meristem (SAM) size; however, the signaling molecules downstream of the CLV pathway remain largely unknown in crops. Here, we found that functional disruption of CsCLV3 peptide and its receptor CsCLV1 both resulted in flowers with extra organs and stumpy fruits in cucumber. A heterotrimeric G protein α-subunit (CsGPA1) was shown to interact with CsCLV1. Csgpa1 mutant plants derived from gene editing displayed significantly increased floral organ numbers and shorter and wider fruits, a phenotype resembling that of Csclv mutants in cucumber. Moreover, the SAM size was enlarged and the longitudinal cell size of fruit was decreased in Csgpa1 mutants. The expression of the classical stem cell regulator WUSCHEL (WUS) was elevated in the SAM, while the expression of the fruit length stimulator CRABS CLAW (CRC) was reduced in the fruit of Csgpa1 mutants. Therefore, the Gα-subunit CsGPA1 protein interacts with CsCLV1 to inhibit floral organ numbers but promote fruit elongation, via repressing CsWUS expression and activating CsCRC transcription in cucumber. Our findings identified a new player in the CLV signaling pathway during flower and fruit development in dicots, increasing the number of target genes for precise manipulation of fruit shape during crop breeding.

14.
Nat Commun ; 15(1): 5151, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886382

RESUMEN

RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.


Asunto(s)
Centrómero , ADN-Topoisomerasas de Tipo I , ADN Satélite , ARN Polimerasa II , Transcripción Genética , Animales , ADN Satélite/genética , ADN Satélite/metabolismo , Humanos , Centrómero/metabolismo , Ratones , ADN-Topoisomerasas de Tipo I/metabolismo , ADN-Topoisomerasas de Tipo I/genética , ARN Polimerasa II/metabolismo , ARN Polimerasa II/genética , Roturas del ADN de Doble Cadena , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Evolución Molecular
15.
J Am Soc Mass Spectrom ; 35(7): 1497-1506, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38828990

RESUMEN

Ion trajectory simulation is a significant and useful tool for understanding ion transfer mechanisms within the first vacuum region of the atmospheric pressure ionization mass spectrometer (API-MS). However, the complex dynamic gas field and wide pressure range lead to inaccurate simulation and huge computational costs. In this work, a novel electrohydrodynamic simulation called the statistical diffusion-hard-sphere (SDHS) mixed collision model was developed for characterizing the ion trajectories. For the first time, the influence of the dynamic pressure on the ion trajectory is considered for simulation, which helps to avoid an intolerable computational cost. Comparing with the conventional Monte Carlo collision model, the SDHS method helps to improve the calculation accuracy of ion trajectories under the first vacuum region and reduce the computational cost for at least 12-folds. Simulation results showed that the maximum ion loss came from the gap of the electrodes. The distance of the capillary-quadrupole ion guide was also a non-negligible factor. The trend of quantitative experimental results matches the SDHS simulation results. The maximum ion transfer efficiencies of quantitative experiment and simulation were 55% and 52%, respectively. Moreover, three ions, caffeine, reserpine, and Ultramark 1621, were measured for evaluating the applicability of SDHS in real API-MS. The trend of experimental results showed good agreement with that of computation. And the results of caffeine further illustrated the reason that the small mass ion transfer efficiency decreased with increasing radio frequency voltage. SDHS method is expected to be useful in the design of ion guides for further improvement of the sensitivity of API-MS.

16.
bioRxiv ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38746280

RESUMEN

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

17.
J Magn Reson Imaging ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38708838

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is associated with increased, and early cardiovascular disease risk. Changes in hemodynamics within the left ventricle (LV) respond to cardiac remodeling. The LV hemodynamics in nondialysis CKD patients are not clearly understood. PURPOSE: To use four-dimensional blood flow MRI (4D flow MRI) to explore changes in LV kinetic energy (KE) and the relationship between LV KE and LV remodeling in CKD patients. STUDY TYPE: Retrospective. POPULATION: 98 predialysis CKD patients (Stage 3: n = 21, stage 4: n = 21, and stage 5: n = 56) and 16 age- and sex-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP) cine sequence, 4D flow MRI with a fast field echo sequence, T1 mapping with a modified Look-Locker SSFP sequence, and T2 mapping with a gradient recalled and spin echo sequence. ASSESSMENT: Demographic characteristics (age, sex, height, weight, blood pressure, heart rate, aortic regurgitation, and mitral regurgitation) and laboratory data (eGFR, Creatinine, hemoglobin, ferritin, transferrin saturation, potassium, and carbon dioxide bonding capacity) were extracted from patient records. Myocardial T1, T2, LV ejection fraction, end diastolic volume (EDV), end systolic volume, LV flow components (direct flow, delayed ejection, retained inflow, and residual volume) and KE parameters (peak systolic, systolic, diastolic, peak E-wave, peak A-wave, E/A ratio, and global) were assessed. The KE parameters were normalized to EDV (KEiEDV). Parameters were compared between disease stage in CKD patients, and between CKD patients and healthy controls. STATISTICAL TESTS: Differences in clinical and imaging parameters between groups were compared using one-way ANOVA, Kruskal Walls and Mann-Whitney U tests, chi-square test, and Fisher's exact test. Pearson or Spearman's correlation coefficients and multiple linear regression analysis were used to compare the correlation between LV KE and other clinical and functional parameters. A P-value of <0.05 was considered significant. RESULTS: Compared with healthy controls, peak systolic (24.76 ± 5.40 µJ/mL vs. 31.86 ± 13.18 µJ/mL), systolic (11.62 ± 2.29 µJ/mL vs. 15.27 ± 5.10 µJ/mL), diastolic (7.95 ± 1.92 µJ/mL vs. 13.33 ± 5.15 µJ/mL), peak A-wave (15.95 ± 4.86 µJ/mL vs. 31.98 ± 14.51 µJ/mL), and global KEiEDV (9.40 ± 1.64 µJ/mL vs. 14.02 ± 4.14 µJ/mL) were significantly increased and the KEiEDV E/A ratio (1.16 ± 0.67 vs. 0.69 ± 0.53) was significantly decreased in CKD patients. As the CKD stage progressed, both diastolic KEiEDV (10.45 ± 4.30 µJ/mL vs. 12.28 ± 4.85 µJ/mL vs. 14.80 ± 5.06 µJ/mL) and peak E-wave KEiEDV (15.30 ± 7.06 µJ/mL vs. 14.69 ± 8.20 µJ/mL vs. 19.33 ± 8.29 µJ/mL) increased significantly. In multiple regression analysis, global KEiEDV (ß* = 0.505; ß* = 0.328), and proportion of direct flow (ß* = -0.376; ß* = -0.410) demonstrated an independent association with T1 and T2 times. DATA CONCLUSION: 4D flow MRI-derived LV KE parameters show altered LV adaptations in CKD patients and correlate independently with T1 and T2 mapping that may represent myocardial fibrosis and edema. TECHNICAL EFFICACY: Stage 3.

18.
Int J Biol Macromol ; 266(Pt 2): 131277, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38565366

RESUMEN

Bacteria-infected wound healing has attracted widespread attention in biomedical engineering. Wound dressing is a potential strategy for repairing infectious wounds. However, the development of wound dressing with appropriate physiochemical, antibacterial, and hemostatic properties, remains challenging. Hence, there is a motivation to develop new synthetic dressings to improve bacteria-infected wound healing. Here, we fabricate a biocompatible sponge through the covalent crosslinking of collagen (Col), quaternized chitosan (QCS), and graphene oxide (GO). The resulting Col-QCS-GO sponge shows an elastic modulus of 1.93-fold higher than Col sponge due to enhanced crosslinking degree by GO incorporation. Moreover, the fabricated Col-QCS-GO sponge shows favorable porosity (84.30 ± 3.12 %), water absorption / retention (2658.0 ± 113.4 % / 1114.0 ± 65.7 %), and hemostasis capacities (blood loss <50.0 mg). Furthermore, the antibacterial property of the Col-QCS-GO sponge under near-infrared (NIR) irradiation is significantly enhanced (the inhibition rates are 99.9 % for S. aureus and 99.9 % for E. coli) due to the inherent antibacterial properties of QCS and the photothermal antibacterial capabilities of GO. Finally, the Col-QCS-GO+NIR sponge exhibits the lowest percentage of wound area (9.05 ± 1.42 %) at day 14 compared to the control group (31.61 ± 1.76 %). This study provides new insights for developing innovative sponges for bacteria-infected wound healing.


Asunto(s)
Antibacterianos , Quitosano , Grafito , Hemostáticos , Cicatrización de Heridas , Animales , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Vendajes , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Quitosano/química , Quitosano/farmacología , Colágeno/química , Colágeno/farmacología , Escherichia coli/efectos de los fármacos , Grafito/química , Grafito/farmacología , Hemostasis/efectos de los fármacos , Hemostáticos/farmacología , Hemostáticos/química , Porosidad , Staphylococcus aureus/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
19.
Adv Mater ; 36(29): e2313297, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38475975

RESUMEN

The 2D electron gas (2DEG) at oxide interfaces exhibits extraordinary properties, such as 2D superconductivity and ferromagnetism, coupled to strongly correlated electrons in narrow d-bands. In particular, 2DEGs in KTaO3 (KTO) with 5d t2g orbitals exhibit larger atomic spin-orbit coupling and crystal-facet-dependent superconductivity absent for 3d 2DEGs in SrTiO3 (STO). Herein, by tracing the interfacial chemistry, weak anti-localization magneto-transport behavior, and electronic structures of (001), (110), and (111) KTO 2DEGs, unambiguously cation exchange across KTO interfaces is discovered. Therefore, the origin of the 2DEGs at KTO-based interfaces is dramatically different from the electronic reconstruction observed at STO interfaces. More importantly, as the interface polarization grows with the higher order planes in the KTO case, the Rashba spin splitting becomes maximal for the superconducting (111) interfaces approximately twice that of the (001) interface. The larger Rashba spin splitting couples strongly to the asymmetric chiral texture of the orbital angular moment, and results mainly from the enhanced inter-orbital hopping of the t2g bands and more localized wave functions. This finding has profound implications for the search for topological superconductors, as well as the realization of efficient spin-charge interconversion for low-power spin-orbitronics based on (110) and (111) KTO interfaces.

20.
J Clin Immunol ; 44(3): 80, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38462559

RESUMEN

OBJECTIVE: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2. METHODS: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted. RESULTS: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts. CONCLUSION: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.


Asunto(s)
COVID-19 , Interferón Tipo I , Anciano , Humanos , Masculino , Autoanticuerpos , COVID-19/epidemiología , SARS-CoV-2 , Prevalencia , China/epidemiología , Anticuerpos Neutralizantes , Antivirales
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