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1.
Plant J ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981001

RESUMEN

Understanding and optimizing the process of grain filling helps the quest to maximize rice (Oryza sativa L.) seed yield and quality, yet the intricate mechanisms at play remain fragmented. Transcription factors (TFs) are major players in the gene networks underlying the grain filling process. Here, we employed grain incomplete filling (OsGIF1)/cell wall invertase 2, a key gene involved in grain filling, to explore its upstream TFs and identified a bZIP family TF, OsbZIP10, to be a transcriptional activator of OsGIF1. Rice grains of the knockouts of OsbZIP10 showed increased white-core rates but lower amylose content (AC), leading to better eating and cooking qualities in all genetic backgrounds investigated, though the impact of mutations in OsbZIP10 on grain weight depended on genetic background. Multi-omics analyses suggested that, in addition to OsGIF1, multiple genes involved in different biological processes contributing to grain filling were targeted by OsbZIP10, including OsAGPS1, a gene encoding the ADP-Glc pyrophosphorylase (AGPase) small subunit, and genes contributing to homeostasis of reactive oxygen species. Distinct genetic make-up was observed in OsbZIP10 between japonica and indica rice varieties, with the majority varieties of each subspecies belonging to two different haplotypes that were closely associated with AC. Overexpressing the haplotype linked to high-AC in the low-AC genetic background increased AC. Overall, this study sheds crucial light on the significance of the OsbZIP10-OsGIF1 module in the determination of rice grain quality, offering a potential avenue for genetic engineering of rice to produce seeds with tailored attributes.

2.
Sensors (Basel) ; 24(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-39001002

RESUMEN

With the emergence of RISC-V architecture in embedded devices, its inherent low-power features have propelled its extensive adoption across various industrial settings. Displacement sensors leveraging Hall sensors and magnetic flux measurement present notable benefits including cost-effectiveness and compact design. This study undertakes the porting of Hall sensors onto RISC-V architecture embedded devices, validating their functionality within displacement sensors. Empirical investigations substantiate that the ported system consistently delivers comparable outcomes to those obtained from x86 architecture systems employing PM-MFM methods, affirming its reliability and performance in practical applications.

3.
Front Genet ; 15: 1429844, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015772

RESUMEN

Mesenchymal stem cells (MSCs) have promising potential for bone tissue engineering in bone healing and regeneration. They are regarded as such due to their capacity for self-renewal, multiple differentiation, and their ability to modulate the immune response. However, changes in the molecular pathways and transcription factors of MSCs in osteogenesis can lead to bone defects and metabolic bone diseases. DNA methylation is an epigenetic process that plays an important role in the osteogenic differentiation of MSCs by regulating gene expression. An increasing number of studies have demonstrated the significance of DNA methyltransferases (DNMTs), Ten-eleven translocation family proteins (TETs), and MSCs signaling pathways about osteogenic differentiation in MSCs. This review focuses on the progress of research in these areas.

4.
Br J Pharmacol ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38877785

RESUMEN

BACKGROUND AND PURPOSE: The adenosine A2A receptor (A2AR) is involved in various physiological and pathological processes in the eye; however, the role of the A2AR signalling in corneal epithelial wound healing is not known. Here, the expression, therapeutic effects and signalling mechanism of A2AR in corneal epithelial wound healing were investigated using the A2AR agonist CGS21680. EXPERIMENTAL APPROACH: A2AR localization and expression during wound healing in the murine cornea were determined by immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. The effect of CGS21680 on corneal epithelial wound healing in the lesioned corneal and cultured human corneal epithelial cells (hCECs) by modulating cellular proliferation and migration was critically evaluated. The role of Hippo-YAP signalling in mediating the CGS21680 effect on wound healing by pharmacological inhibition of YAP signalling was explored. KEY RESULTS: A2AR expression was up-regulated after corneal epithelial injury. Topical administration of CGS21680 dose-dependently promoted corneal epithelial wound healing in the injured corneal epithelium by promoting cellular proliferation. Furthermore, CGS21680 accelerated the cellular proliferation and migration of hCECs in vitro. A2AR activation promoted early up-regulation and later down-regulation of YAP signalling molecules, and pharmacological inhibition of YAP signalling reverted CGS21680-mediated wound healing effect in vivo and in vitro. CONCLUSION AND IMPLICATIONS: A2AR activation promotes wound healing by enhancing cellular proliferation and migration through the YAP signalling pathway. A2ARs play an important role in the maintenance of corneal epithelium integrity and may represent a novel therapeutic target for facilitating corneal epithelial wound healing.

5.
Sensors (Basel) ; 24(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38894078

RESUMEN

The paper presents a wide-bandwidth, low-polarization semiconductor optical amplifier (SOA) based on strained quantum wells. By enhancing the material gain of quantum wells for TM modes, we have extended the gain bandwidth of the SOA while reducing its polarization sensitivity. Through a combination of tilted waveguide design and cavity surface optical thin film design, we have effectively reduced the cavity surface reflectance of the SOA, thus decreasing device transmission losses and noise figure. At a wavelength of 1550 nm and a drive current of 1.4 A, the output power can reach 188 mW, with a small signal gain of 36.4 dB and a 3 dB gain bandwidth of 128 nm. The linewidth broadening is only 1.032 times. The polarization-dependent gain of the SOA is below 1.4 dB, and the noise figure is below 5.5 dB. The device employs only I-line lithography technology, offering simple fabrication processes and low costs yet delivering outstanding and stable performance. The designed SOA achieves wide gain bandwidth, high gain, low polarization sensitivity, low linewidth broadening, and low noise, promising significant applications in the wide-bandwidth optical communication field across the S + C + L bands.

6.
Carbohydr Polym ; 339: 122216, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823901

RESUMEN

Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.


Asunto(s)
Heparina de Bajo-Peso-Molecular , Control de Calidad , Heparina de Bajo-Peso-Molecular/química , Humanos , Animales , Anticoagulantes/química , Anticoagulantes/farmacología
7.
Int J Nanomedicine ; 19: 5739-5761, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882545

RESUMEN

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation.


Asunto(s)
Neoplasias , Proteolisis , Humanos , Neoplasias/tratamiento farmacológico , Proteolisis/efectos de los fármacos , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Nanopartículas/química , Nanomedicina/métodos , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química
8.
Endocr Relat Cancer ; 31(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38904412

RESUMEN

Scientific evidence has linked diabetes to a higher incidence and increased aggressiveness of breast cancer; however, mechanistic studies of the numerous regulators involved in this process are insufficiently thorough. Advanced glycation end products (AGEs) play an important role in the chronic complications of diabetes, but the mechanisms of AGEs in breast cancer are largely unexplored. In this study, we first demonstrate that high AGE levels in breast cancer tissues are associated with the diabetic state and poor patient outcomes. Furthermore, AGEs interact with the receptor for AGEs (RAGE) to promote breast cancer cell migration and invasion. Mechanistically, based on RNA sequencing (RNA-seq) analysis, we reveal that growth arrest and DNA damage gene 45α (GADD45α) is a vital protein upregulated by AGEs through a P53-dependent pathway. Next, GADD45α recruits thymine DNA glycosylase for base excision repair to form the demethylation complex at the promoter region of MMP-9 and enhance MMP-9 transactivation through DNA demethylation. Overall, our results indicate a critical regulatory role of AGEs in patients with breast cancer and diabetes and reveal a novel mechanism of epigenetic modification in promoting breast cancer metastasis.


Asunto(s)
Neoplasias de la Mama , Proteínas de Ciclo Celular , Productos Finales de Glicación Avanzada , Metaloproteinasa 9 de la Matriz , Regiones Promotoras Genéticas , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Productos Finales de Glicación Avanzada/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Reparación del ADN , Metástasis de la Neoplasia , Línea Celular Tumoral , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Animales , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Persona de Mediana Edad , Proteinas GADD45
9.
Nanomaterials (Basel) ; 14(11)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38869594

RESUMEN

Polarization-insensitive semiconductor optical amplifiers (SOAs) in all-optical networks can improve the signal-light quality and transmission rate. Herein, to reduce the gain sensitivity to polarization, a multi-quantum-well SOA in the 1550 nm band is designed, simulated, and developed. The active region mainly comprises the quaternary compound InGaAlAs, as differences in the potential barriers and wells of the components cause lattice mismatch. Consequently, a strained quantum well is generated, providing the SOA with gain insensitivity to the polarization state of light. In simulations, the SOA with ridge widths of 4 µm, 5 µm, and 6 µm is investigated. A 3 dB gain bandwidth of >140 nm is achieved with a 4 µm ridge width, whereas a 6 µm ridge width provides more output power and gain. The saturated output power is 150 mW (21.76 dB gain) at an input power of 0 dBm but increases to 233 mW (13.67 dB gain) at an input power of 10 dBm. The polarization sensitivity is <3 dBm at -20 dBm. This design, which achieves low polarization sensitivity, a wide gain bandwidth, and high gain, will be applicable in a wide range of fields following further optimization.

10.
FEBS J ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924469

RESUMEN

The arrest of neural crest-derived sympathoadrenal neuroblast differentiation contributes to neuroblastoma formation, and overriding this blocked differentiation is a clear strategy for treating high-risk neuroblastoma. A better understanding of neuroblast or neuroblastoma differentiation is essential for developing new therapeutic approaches. It has been proposed that Krueppel-like factor 7 (KLF7) is a neuroblastoma super-enhancer-associated transcription factor gene. Moreover, KLF7 was found to be intensely active in postmitotic neuroblasts of the developing nervous system during embryogenesis. However, the role of KLF7 in the differentiation of neuroblast or neuroblastoma is unknown. Here, we find a strong association between high KLF7 expression and favorable clinical outcomes in neuroblastoma. KLF7 induces differentiation of neuroblastoma cells independently of the retinoic acid (RA) pathway and acts cooperatively with RA to induce neuroblastoma differentiation. KLF7 alters the GTPase activity and multiple differentiation-related genes by binding directly to the promoters of neuroblast differentiation-associated protein (AHNAK and AHNAK2) and glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5) and regulating their expression. Furthermore, we also observe that silencing KLF7 in neuroblastoma cells promotes the adrenergic-to-mesenchymal transition accompanied by changes in enhancer-mediated gene expression. Our results reveal that KLF7 is an inducer of neuroblast or neuroblastoma differentiation with prognostic significance and potential therapeutic value.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38917051

RESUMEN

BACKGROUND: Understanding the implications of either nonoperative or operative treatment of developmental dysplasia of the hip (DDH) performed before periacetabular osteotomy (PAO) is critical to counseling patients and their families. There are limited studies, however, on PAO for the treatment of residual DDH after surgical intervention during childhood, and even less information about PAO after prior nonoperative treatment. QUESTIONS/PURPOSES: We analyzed patients who had undergone PAO for DDH and asked: Did patients with prior childhood treatment (either operative or nonoperative) (1) improve less in modified Harris hip score (mHHS), 12-item International Hip Outcome Tool (iHOT-12) score, or WOMAC score; (2) demonstrate more severe preoperative deformities; and (3) receive less complete radiographic correction and have more frequent complications than did patients whose hips had not undergone prior treatment? We also asked: (4) Were there subgroup differences among patients with DDH treated nonoperatively versus operatively before PAO in these same functional and radiographic parameters? METHODS: Between January 2011 and December 2020, a total of 90 PAOs were performed in 82 patients who had prior surgical or nonsurgical treatment. Of those, 3 patients (3 hips) with neuromuscular diseases were excluded, 4 patients (5 hips) were excluded for having received treatment after childhood, 7 hips that had undergone bilateral PAOs were excluded, and another 4 patients (4 hips) were lost to follow-up before the minimum study period of 2 years, leaving 71 patients (71 hips) for analysis (the previous treatment group). Among these, 32 patients had a history of previous surgery (the previous surgery group), and 39 patients had prior nonsurgical treatment (such as a Pavlik harness, closed reduction, spica casting) (the previous nonoperative group). During the same period, 1109 PAOs were performed in 956 patients who had no history of previous hip treatment. Following a 1:2 ratio, 142 patients (142 hips) were selected as the control group by matching for age (within 2 years difference), year of surgery (same year), and follow-up time (within 1-year difference). The patient characteristics for both the previous treatment group and the control group exhibited comparability, with mean ± SD follow-up durations of 49 ± 23 months and 48 ± 19 months, respectively. Within the previous 5 years, 3 patients (8%) in the previous nonoperative group, 4 patients (13%) in the previous surgery group, and 15 patients (11%) in the control group had not attended follow-up visits. We compared hip function and radiographic results between the two groups and performed a subgroup analysis between the previous surgery group and the previous nonoperative group. Hip function was assessed using the mHHS questionnaire, the WOMAC, and the iHOT-12 with attention to the minimum clinically important differences of these tools. The threshold values for clinically important improvement were 9.6 points, 13 points, and 16.1 points for the mHHS, iHOT-12, and WOMAC, respectively. Radiographic measurements included the lateral center-edge angle (LCEA), anterior center-edge angle (ACEA), Tönnis angle, acetabulum-head index, and acetabular wall index. We also evaluated Tönnis osteoarthritis grade and femoral head deformity. Occurrences of adverse radiographic events such as posterior column fracture, nonunion, stress fractures, insufficient coverage or overcoverage, acetabular protrusion, and progression of osteoarthritis were recorded. RESULTS: We found no clinically important differences in magnitude of improvement between the previous treatment group and the control group in terms of mHHS (mean ± SD 10 ± 12 versus 12 ± 12; p = 0.36), iHOT-12 (25 ± 18 versus 26 ± 19; p = 0.51), or WOMAC score (12 ± 12 versus 15 ± 19; p = 0.17). Preoperative deformity in the previous treatment group was more severe than in the control group (mean ± SD LCEA -1° ± 9° versus 5° ± 8°; ACEA -8° ± 18° versus 1° ± 14°; Tönnis angle 31° ± 7° versus 27° ± 7°; acetabulum-head index 56% ± 13% versus 61% ± 8%; all p < 0.001). In the previous treatment group, a higher percentage of patients exhibited flattening or irregularity of the femoral head compared with the control group (52% versus 9%; p < 0.001), and there was also a higher proportion of patients with Tönnis grade 1 or above (51% versus 42%; p < 0.001). Although there were still differences in LCEA, ACEA, and Tönnis angle between the two groups at the last follow-up, the differences were small, and the mean values were within the normal range. The previous treatment group had a higher risk of intraoperative posterior column fracture (14% and 5%; p = 0.02), insufficient acetabular coverage (20% and 8%; p = 0.01), and progression of osteoarthritis (17% and 8%; p = 0.04) compared with the control group. Subgroup analysis revealed no clinically important differences in magnitude of improvement between the previous surgery group and the previous nonoperative group in terms of mHHS (10 ± 14 versus 10 ± 11; p = 0.91), iHOT-12 (22 ± 21 versus 27 ± 14; p = 0.26), or WOMAC score (12 ± 14 versus 12 ± 11; p = 0.94). Apart from a higher proportion of patients who presented with arthritis (72% versus 34%; p = 0.01) and a smaller anterior wall index (11% ± 11% versus 20% ± 12%; p = 0.01) in the previous surgery group, all other preoperative radiographic parameters were consistent between the two groups. Additionally, the previous surgery group had a higher frequency of arthritis progression (28% versus 8%; p = 0.02), while the frequencies of other complications were similar between the two groups. Specifically, the frequencies of pubic ramus nonunion (22% versus 21%; p = 0.89), intraoperative posterior column fracture (19% versus 10%; p = 0.50), and insufficient acetabular coverage (25% versus 15%; p = 0.31) were high in both groups. CONCLUSION: We found no clinically important difference in the magnitude of improvement between patients who had childhood treatment and those who did not, but patients who had prior childhood treatment were more likely to experience serious complications, and radiographic correction in those patients was less complete. As in the case of patients who have had prior operative treatments, it is crucial not to overlook the unexpectedly severe deformity of residual DDH after previous nonoperative treatment and complications following PAO. Surgeons and patients alike should be aware of the potential for worse radiographic outcomes or an increased risk of complications when prior operative or nonoperative treatment has preceded PAO. Future studies might investigate optimal management strategies for this specific group of patients to improve outcomes and reduce complications. LEVEL OF EVIDENCE: Level III, therapeutic study.

12.
BMC Ecol Evol ; 24(1): 63, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38741051

RESUMEN

The geographical and ecological patterns of morphological disparity are crucial to understand how species are assembled within communities in the context of the evolutionary history, morphological evolution and ecological interactions. However, with limited exceptions, rather few studies have been conducted on the global pattern of disparity, particularly in early land plants. Here we explored the spatial accumulation of disparity in a morphologically variable and species rich liverwort genus Frullania in order to test the hypothesis of latitude disparity gradient. We compiled a morphological data set consisting of eight continuous traits for 244 currently accepted species, and scored the species distribution into 19 floristic regions worldwide. By reconstructing the morphospace of all defined regions and comparisons, we identified a general Gondwana-Laurasia pattern of disparity in Frullania. This likely results from an increase of ecological opportunities and / or relaxed constraints towards low latitudes. The lowest disparity occurred in arid tropical regions, largely due to a high extinction rate as a consequence of paleoaridification. There was weak correlation between species diversity and disparity at different spatial scales. Furthermore, long-distance dispersal may have partially shaped the present-day distribution of Frullania disparity, given its frequency and the great contribution of widely distributed species to local morphospace. This study not only highlighted the crucial roles of paleoenvironmental changes, ecological opportunities, and efficient dispersal on the global pattern of plant disparity, but also implied its dependence on the ecological and physiological function of traits.


Asunto(s)
Hepatophyta , Hepatophyta/genética , Evolución Biológica , Biodiversidad , Dispersión de las Plantas
13.
J Sep Sci ; 47(9-10): e2300867, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38726736

RESUMEN

Shengxian decoction, a traditional Chinese medicinal prescription, has been shown to alleviate doxorubicin-induced chronic heart failure. This study established an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to separate and characterize the complex chemical compositions of Shengxian decoction, and the absorbed compounds in the bio-samples of the cardiotoxicity rats with chronic heart failure after its oral delivery. Note that 116 chemical compounds were identified from Shengxian decoction in vitro, 81 more than previously detected. Based on the three-dimensional data of these compounds, 28 absorbed compounds were confirmed in vivo. Network pharmacology and molecular docking experiments indicated that timosaponin B-II, timosaponin A-III, gitogenin, and 7,8-didehydrocimigenol were recognized as the key effective compounds to exert effects against doxorubicin cardiotoxicity by acting on targets such as caspase 3, cyclin-dependent kinase 1, cyclin-dependent kinase 4, receptor tyrosine-protein kinase erbB-2, and mitogen-activated protein kinase 1 in p53 and phosphatidylinositol 3-kinase-Akt signaling pathways. This study developed the understanding of the composition of Shengxian decoction for the treatment of doxorubicin cardiotoxicity, as well as a feasible strategy to elucidate the effective constituents in traditional Chinese medicines.


Asunto(s)
Doxorrubicina , Medicamentos Herbarios Chinos , Farmacología en Red , Ratas Sprague-Dawley , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/análisis , Animales , Ratas , Cromatografía Líquida de Alta Presión , Masculino , Espectrometría de Masas , Cardiotoxicidad , Simulación del Acoplamiento Molecular , Combinación de Medicamentos
14.
mBio ; 15(6): e0350423, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38747587

RESUMEN

Successful host tissue colonization is crucial for fungal pathogens to cause mycosis and complete the infection cycle, in which fungal cells undergo a series of morphological transition-included cellular events to combat with hosts. However, many transcription factors (TFs) and their mediated networks regulating fungal pathogen colonization of host tissue are not well characterized. Here, a TF (BbHCR1)-mediated regulatory network was identified in an insect pathogenic fungus, Beauveria bassiana, that controlled insect hemocoel colonization. BbHCR1 was highly expressed in fungal cells after reaching insect hemocoel and controlled the yeast (in vivo blastospores)-to-hyphal morphological switch, evasion of immune defense response, and fungal virulence. Comparative analysis of RNA sequencing and chromatin immunoprecipitation sequencing identified a core set of BbHCR1 target genes during hemocoel colonization, in which abaA and brlA were targeted to limit the rapid switch from blastospores to hyphae and fungal virulence. Two targets encoding hypothetical proteins, HP1 and HP2, were activated and repressed by BbHCR1, respectively, which acted as a virulence factor and repressor, respectively, suggesting that BbHCR1 activated virulence factors but repressed virulence repressors during the colonization of insect hemocoel. BbHCR1 tuned the expression of two dominant hemocoel colonization-involved metabolite biosynthetic gene clusters, which linked its regulatory role in evasion of immune response. Those functions of BbHCR1 were found to be collaboratively regulated by Fus3- and Hog1-MAP kinases via phosphorylation. These findings have drawn a regulatory network in which Fus3- and Hog1-MAP kinases phosphorylate BbHCR1, which in turn controls the colonization of insect body cavities by regulating fungal morphological transition and virulence-implicated genes.IMPORTANCEFungal pathogens adopt a series of tactics for successful colonization in host tissues, which include morphological transition and the generation of toxic and immunosuppressive molecules. However, many transcription factors (TFs) and their linked pathways that regulate tissue colonization are not well characterized. Here, we identified a TF (BbHCR1)-mediated regulatory network that controls the insect fungal pathogen, Beauveria bassiana, colonization of insect hemocoel. During these processes, BbHCR1 targeted the fungal central development pathway for the control of yeast (blastospores)-to-hyphae morphological transition, activated virulence factors, repressed virulence repressors, and tuned the expression of two dominant hemocoel colonization-involved immunosuppressive and immunostimulatory metabolite biosynthetic gene clusters. The BbHCR1 regulatory function was governed by Fus3- and Hog1-MAP kinases. These findings led to a new regulatory network composed of Fus3- and Hog1-MAP kinases and BbHCR1 that control insect body cavity colonization by regulating fungal morphological transition and virulence-implicated genes.


Asunto(s)
Beauveria , Proteínas Fúngicas , Regulación Fúngica de la Expresión Génica , Redes Reguladoras de Genes , Factores de Transcripción , Animales , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Beauveria/genética , Beauveria/patogenicidad , Virulencia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Insectos/microbiología , Hifa/crecimiento & desarrollo , Hifa/genética , Interacciones Huésped-Patógeno
15.
J Obstet Gynaecol Can ; 46(7): 102562, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759792

RESUMEN

OBJECTIVES: To characterise contemporary trends in the hormonal management of endometriosis in adolescent and young adult patients with biopsy-proven endometriosis. METHODS: Retrospective chart review of women aged 14-25 years who underwent laparoscopy for pelvic pain with biopsy-proven endometriosis between January 2011 and September 2020 at an academic tertiary hospital system. The final sample included 91 patients with biopsy-confirmed endometriosis. RESULTS: Combined oral contraceptives (COCs) were the most common initial treatment (64% of patients). Progestin-only formulations (low- and high-dose norethindrone acetate) were offered to younger patients (age 15.9 ± 2.7 years) than those offered COCs (19.9 ± 3.3 years) and levonorgestrel intrauterine devices (LNG-IUDs) (21.9 ± 1.7 years). Current treatments varied widely and included COCs (32%), LNG-IUDs (18%), oral progestins (low- and high-dose norethindrone, medroxyprogesterone) (14%), elagolix (9%), and leuprolide (8%). Oral adjuncts to LNG-IUD were common: usually low- or high-dose norethindrone (37% of patients with an LNG-IUD), but also included progesterone, COCs, and elagolix. CONCLUSIONS: Oral progestins, LNG-IUDs, and COCs were the mainstay of initial treatment. Subsequent treatments varied widely and included COCs, LNG-IUDs, oral progestins, elagolix, leuprolide, and combinations of these agents. We observed that most young women switched between therapies, suggesting that a personalised approach is often used to determine treatment plans among the wide range of options currently available. This study helps define the spectrum of treatment regimens for endometriosis in adolescent females.


Asunto(s)
Anticonceptivos Orales Combinados , Endometriosis , Dispositivos Intrauterinos Medicados , Levonorgestrel , Humanos , Femenino , Endometriosis/tratamiento farmacológico , Endometriosis/patología , Endometriosis/cirugía , Adolescente , Adulto Joven , Estudios Retrospectivos , Adulto , Levonorgestrel/administración & dosificación , Levonorgestrel/uso terapéutico , Anticonceptivos Orales Combinados/uso terapéutico , Biopsia , Progestinas/uso terapéutico , Progestinas/administración & dosificación , Noretindrona/uso terapéutico , Noretindrona/administración & dosificación , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología
16.
Heliyon ; 10(9): e30005, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38694048

RESUMEN

The impact of hyperoxia-induced brain injury in preterm infants is being increasingly investigated. However, the parameters and protocols used to study this condition in animal models lack consistency. Research is further hampered by the fact that hyperoxia exerts both direct and indirect effects on oligodendrocytes and neurons, with the precise underlying mechanisms remaining unclear. In this article, we aim to provide a comprehensive overview of the conditions used to induce hyperoxia in animal models of immature brain injury. We discuss what is known regarding the mechanisms underlying hyperoxia-induced immature brain injury, focusing on the effects on oligodendrocytes and neurons, and briefly describe therapies that may counteract the effects of hyperoxia. We also identify further studies required to fully elucidate the effects of hyperoxia on the immature brain as well as discuss the leading therapeutic options.

17.
Nanomaterials (Basel) ; 14(9)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38727381

RESUMEN

Broad-area lasers (BALs) have found applications in a variety of crucial fields on account of their high output power and high energy transfer efficiency. However, they suffer from poor spatial beam quality due to multi-mode behavior along the waveguide transverse direction. In this paper, we propose a novel metasurface waveguide structure acting as a transverse mode selective back-reflector for BALs. In order to effectively inverse design such a structure, a digital adjoint algorithm is introduced to adapt the considerably large design area and the high degree of freedom. As a proof of the concept, a device structure with a design area of 40 × 20 µm2 is investigated. The simulation results exhibit high fundamental mode reflection (above 90%), while higher-order transverse mode reflections are suppressed below 0.2%. This is, to our knowledge, the largest device structure designed based on the inverse method. We exploited such a device and the method and further investigated the device's robustness and feasibility of the inverse method. The results are elaborately discussed.

18.
Life (Basel) ; 14(5)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38792616

RESUMEN

Soil salinization poses a threat to the sustainability of agricultural production and has become a global issue. Cotton is an important cash crop and plays an important role in economic development. Salt stress has been harming the yield and quality of many crops, including cotton, for many years. In recent years, soil salinization has been increasing. It is crucial to study the mechanism of cotton salt tolerance and explore diversified materials and methods to alleviate the salt stress of cotton for the development of the cotton industry. Nanoparticles (NPs) are an effective means to alleviate salt stress. In this study, zinc oxide NPs (ZnO NPs) were sprayed on cotton leaves with the aim of investigating the intrinsic mechanism of NPs to alleviate salt stress in cotton. The results show that the foliar spraying of ZnO NPs significantly alleviated the negative effects of salt stress on hydroponic cotton seedlings, including the improvement of above-ground and root dry and fresh weight, leaf area, seedling height, and stem diameter. In addition, ZnO NPs can significantly improve the salt-induced oxidative stress by reducing the levels of MDA, H2O2, and O2- and increasing the activities of major antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Furthermore, RNA-seq showed that the foliar spraying of ZnO NPs could induce the expressions of CNGC, NHX2, AHA3, HAK17, and other genes, and reduce the expression of SKOR, combined with the CBL-CIPK pathway, which alleviated the toxic effect of excessive Na+ and reduced the loss of excessive K+ so that the Na+/K+ ratio was stabilized. In summary, our results indicate that the foliar application of ZnO NPs can alleviate high salt stress in cotton by adjusting the Na+/K+ ratio and regulating antioxidative ability. This provides a new strategy for alleviating the salt stress of cotton and other crops, which is conducive to the development of agriculture.

19.
Front Med (Lausanne) ; 11: 1357824, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737764

RESUMEN

Premature ovarian insufficiency (POI) is a condition characterized by menstrual disturbance, subfertility, and estrogen deficiency symptoms. Women with POI have a small chance of natural conception, which may be even smaller when complicated with unilateral ovarian due to reduction of the ovarian follicular reserve. In China, acupuncture has been widely used to treat POI and POI-induced infertility, and studies have shown that acupuncture is helpful for improving ovarian function. Thread-embedding therapy is a method of acupuncture treatment development and extension, which can make the acupuncture effect last. In this article, we report a patient diagnosed with POI after unilateral oophorectomy (UO) who spontaneously conceived after thread-embedding therapy. Thread-embedding therapy may improve ovarian function in patients with POI, thereby providing a treatment strategy for infertility in patients with POI. This case report was written in accordance with the CARE guidelines.

20.
Microbiol Spectr ; 12(6): e0391423, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38742903

RESUMEN

Porcine parvovirus (PPV) is one of the most important pathogens that cause reproductive failure in pigs. However, the pathogenesis of PPV infection remains unclear. Proteomics is a powerful tool to understand the interaction between virus and host cells. In the present study, we analyzed the proteomics of PPV-infected PK-15 cells. A total of 32 and 345 proteins were differentially expressed at the early and replication stages, respectively. Subsequent gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed these differentially expressed proteins were significantly enriched in pathways including toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and viral carcinogenesis. The expression of poly (rC) binding protein 1 (PCBP1) was observed to decrease after PPV infection. Overexpressed or silenced PCBP1 expression inhibited or promoted PPV infection. Our studies established a foundation for further exploration of the multiplication mechanism of PPV. IMPORTANCE: Porcine parvovirus (PPV) is a cause of reproductive failure in the swine industry. Our knowledge of PPV remains limited, and there is no effective treatment for PPV infection. Proteomics of PPV-infected PK-15 cells was conducted to identify differentially expressed proteins at 6 hours post-infection (hpi) and 36 hpi. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that various pathways participate in PPV infection. Poly (rC) binding protein 1 was confirmed to inhibit PPV replication, which provided potential targets for anti-PPV infection. Our findings improve the understanding of PPV infection and pave the way for future research in this area.


Asunto(s)
Infecciones por Parvoviridae , Parvovirus Porcino , Proteómica , Proteínas de Unión al ARN , Enfermedades de los Porcinos , Replicación Viral , Parvovirus Porcino/genética , Parvovirus Porcino/fisiología , Animales , Porcinos , Línea Celular , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Infecciones por Parvoviridae/virología , Infecciones por Parvoviridae/metabolismo , Infecciones por Parvoviridae/veterinaria , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/metabolismo , Enfermedades de los Porcinos/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo
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