Eradication of bacterial infection requires timely and appropriate immune and inflammatory responses, but excessive induction of inflammatory cytokines can cause acute or chronic inflammatory ...disorders. Thus, various layers of negative regulators and mechanisms are needed to ensure maintenance of the homeostasis for the immune system. miRNAs are a family of small non-coding RNAs that emerged as significant and versatile regulators involved in regulation of immune responses. Recently, the molecular mechanisms of miRNA in host-pathogen interaction networks have been extensively studied in mammals, whereas the underlying regulatory mechanisms in fish are still poorly understood. In this study, we identify miR-21 as a negative regulator of the teleost inflammatory response. We found that lipopolysaccharide and
significantly upregulated the expression of fish miR-21. Upregulated miR-21 suppresses LPS-induced inflammatory cytokine expression by targeting IL-1 receptor-associated kinase 4 (IRAK4), thereby avoiding excessive inflammatory responses. Furthermore, we demonstrated that miR-21 regulates inflammatory responses through NF-κB signaling pathways. The collective findings indicate that miR-21 plays a regulatory role in host-pathogen interactions through IRAK4-mediated NF-κB signaling pathway.
To assess the effectiveness and safety of combining intravitreal endothelial growth factor inhibitor (anti-VEGF) and ocular corticosteroids for diabetic macular edema (DME).
Articles concentrating on ...the efficacy and safety of combining anti-VEGF and ocular corticosteroids therapy for DME versus anti-VEGF monotherapy was screened systematically. Meta-analysis was conducted on the basis of a protocol registered in the PROSPERO (CRD42023408338) and performed on the extracted continuous variables and dichotomous variables. The outcome was expressed as weighted mean difference (MD) and risk ratio (RR).
Add up to 21 studies including 1468 eyes were enrolled in this study. The MD for best-corrected visual acuity (BCVA) improvement at 1/3/6/12-month between the combination therapy group and monotherapy group were 2.56 (95% CI 0.43, 4.70), 2.46 (95% CI −0.40, 5.32), − 1.76 (95% CI −3.18, −0.34), − 1.94 (95% CI −3.87, 0.00), respectively. The MD for central retinal thickness (CMT) reduction at 1/3/6/12-month between two groups were − 66.27 (95% CI −101.08, −31.47), − 33.62 (95% CI −57.55, −9.70), − 4.54 (95% CI −16.84, 7.76), − 26.67 (95% CI −41.52, −11.82), respectively. Additionally, the combination group had higher relative risk of high intraocular pressure and cataract progression events.
Anti-VEGF combined with ocular corticosteroids had a significant advantage over anti-VEGF monotherapy within 3 months of DME treatment, which reached the maximum with increasing anti-VEGF injection times to 3. However, with the prolongation of the treatment cycle, the effect of combined therapy after 6 months was no better than monotherapy, and the side effects of combined therapy were more severe.
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With the widespread clinical application of the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L), whether the questionnaire scores are responsive to changes in patients' ...health and how much changes in questionnaire scores represent patients' real health changes require consideration. Consequently, we assessed responsiveness and estimated the minimal clinically important difference (MCID) of the EQ-5D-5L in surgically treated patients with cervical intraepithelial neoplasia (CIN) to determine the relationship between MCID and minimal detectable change (MDC).
We conducted a longitudinal, observational study. Participants were patients with CIN from the gynecology inpatient department of a grade-A tertiary hospital in Shihezi, Xinjiang, China. Participants completed the EQ-5D-5L and the Global Rating of Change Questionnaire (GRCQ) at baseline and one month post-surgery. The Wilcoxon signed-rank test was used to compare EQ-5D-5L scores pre- and post-treatment. We calculated the effect size (ES) and the standardized response mean (SRM) to quantitatively assess responsiveness. Distribution-based, anchor-based, and instrument-defined methods were used to estimate MCID. MCID to MDC ratios at individual- and group-levels were also calculated.
Fifty patients with CIN completed the follow-up investigation (mean age 44.76 ± 8.72 years; mean follow-up time 32.28 ± 1.43 days). The index value and EQ visual analogue scale (EQ VAS) of the EQ-5D-5L improved by 0.025 and 6.92 (all p < 0.05) at follow-up as compared to baseline respectively. The ES and the SRM of the index value were 0.47 and 0.42 respectively, indicating small responsiveness; while the ES and the SRM of EQ VAS were 0.50 and 0.49 respectively, indicating small to moderate responsiveness. The average (range) of MCIDs for index value and EQ VAS were 0.039 (0.023-0.064) and 5.35 (3.12-6.99) respectively. These values can only be used to determine whether patients have experienced clinically meaningful health improvements at the group level.
The EQ-5D-5L has only small to moderate responsiveness in post-surgical patients with CIN, and the MCIDs developed in this study can be used for group-level health assessment. However, further study is needed concerning health changes at the individual level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Food safety problems caused by pesticide residues have always been a concern for many people. In this study, we investigated the uptake, translocation and subcellular distribution of neonicotinoid ...insecticides, triazole fungicides, and sulfonylurea herbicides in rice plants (Oryza sativa L.). The time-dependent uptake kinetics of the three categories of pesticides with different molecular structures fit a first-order one-compartment kinetic model. The neonicotinoids (log Kow −0.66–0.8) were mainly concentrated in the leaves, and the triazoles (log Kow 3.72–4.4) were mainly concentrated in the roots. Neonicotinoid pesticides in the roots were preferentially transported across the membrane through the symplastic pathway; triazole pesticides except for triadimefon and myclobutanil preferentially passed through the symplastic pathway; and sulfonylurea pesticides (log Kow 0.034–2.89) were first transported upward through the apoplastic pathway. In the roots, neonicotinoids, triazoles, and sulfonylurea herbicides were mainly concentrated in the soluble fractions, cell wall and apoplast fractions, respectively. In addition, there was a high positive correlation between the subcellular distribution of pesticides in the roots, stems and leaves. Molecular weight and log Kow jointly affected the enrichment of triazole pesticides in the roots, stems and leaves and the transfer from stems to leaves, while water solubility and log Kow commonly affected neonicotinoids. There was a correlation between pesticide absorption and the molecular structures of pesticides. To develop pesticides with strong uptake and transport capabilities, it is necessary to consider that the electronegativity of some atoms is stronger, the sum of the topological indices of heteroatoms can be large, and the van der Waals volume increases accordingly.
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•Pesticides with different structures have different absorption characteristics.•Subcellular distribution of pesticides in root is positive correlation with that of stem and leaf.•MATSe5, MATSv5, ATSp7, Shet and QNmax determine systemic activity of pesticides.
BACKGROUND: Low phosphorus (P) availability is a major constraint to soybean growth and production. Developing P-efficient soybean varieties that can efficiently utilize native P and added P in the ...soils would be a sustainable and economical approach to soybean production. SCOPE: This review summarizes the possible mechanisms for P efficiency and genetic strategies to improve P efficiency in soybean with examples from several case studies. It also highlights potential obstacles and depicts future perspectives in 'root breeding'. CONCLUSIONS: This review provides new insights into the mechanisms of P efficiency and breeding strategies for this trait in soybean. Root biology is a new frontier of plant biology. Substantial efforts are now focusing on increasing soybean P efficiency through 'root breeding'. To advance this area, additional collaborations between plant breeders and physiologists, as well as applied and theoretical research are needed to develop more soybean varieties with enhanced P efficiency through root modification, which might contribute to reduced use of P fertilizers, expanding agriculture on low-P soils, and achieving more sustainable agriculture.
Root architecture plays important roles in plant water and nutrient acquisition. However, accurate modeling of the root system that provides a realistic representation of roots in the soil is limited ...by a lack of appropriate tools for the non-destructive and precise measurement of the root system architecture in situ. Here we describe a root growth system in which the roots grow in a solid gel matrix that was used to reconstruct 3D root architecture in situ and dynamically simulate its changes under various nutrient conditions with a high degree of precision. A 3D laser scanner combined with a transparent gel-based growth system was used to capture 3D images of roots. The root system skeleton was extracted using a skeleton extraction method based on the Hough transformation, and mesh modeling using Ball-B spline was employed. We successfully used this system to reconstruct rice and soybean root architectures and determine their changes under various phosphorus (P) supply conditions. Our results showed that the 3D root architecture parameters that were dynamically calculated based on the skeletonization and simulation of root systems were significantly correlated with the biomass and P content of rice and soybean based on both the simulation system and previous reports. Therefore, this approach provides a novel technique for the study of crop root growth and its adaptive changes to various environmental conditions.
Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide‐binding oligomerization domain‐like receptor family ...pyrin domain‐containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti‐inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood–brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), cleaved caspase‐1, interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6); these changes were also associated with an increase in the anti‐apoptotic factor (Bcl2) and reduction in the pro‐apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome‐associated apoptosis.
Low phosphorus (P) availability is a major constraint to crop growth and production, including soybean (Glycine max), on a global scale. However, 50% to 80% of the total P in agricultural soils ...exists as organic phosphate, which is unavailable to plants unless hydrolyzed to release inorganic phosphate. One strategy for improving crop P nutrition is the enhanced activity of acid phosphatases (APases) to obtain or remobilize inorganic phosphate from organic P sources. In this study, we overexpressed an Arabidopsis (Arabidopsis ihaliana) purple APase gene (AtPAPIS) containing a carrot (Daucus carota) extracellular targeting peptide in soybean hairy roots and found that the APase activity was increased by 1.5-fold in transgenic hairy roots. We subsequently transformed soybean plants with AtPAP15 and studied three homozygous overexpression lines of AtPAP15. The three transgenic lines exhibited significantly improved P efficiency with 117.8%, 56.5%, and 57.8% increases in plant dry weight, and 90.1%, 18.2%, and 62.6% increases in plant P content, respectively, as compared with wild-type plants grown on sand culture containing phytate as the sole P source. The transgenic soybean lines also exhibited a significant level of APase and phytase activity in leaves and root exudates, respectively. Furthermore, the transgenic lines exhibited improved yields when grown on acid soils, with 35.9%, 41.0%, and 59.0% increases in pod number per plant, and 46.0%, 48.3%, and 66.7% increases in seed number per plant. Taken together, to our knowledge, our study is the first report on the improvement of Ñ efficiency in soybean through constitutive expression of a plant APase gene. These findings could have significant implications for improving crop yield on soils low in available P, which is a serious agricultural limitation worldwide.
Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling. This signaling is typically generated at cell ...surface receptors, the activation of which results in the translocation of STATs to the nucleus. STATs are involved in biological events as diverse as embryonic development, programmed cell death, organogenesis, innate immunity, adaptive immunity and cell growth regulation in organisms ranging from slime molds to insects to humans. Numerous studies have demonstrated the activation of STAT3 in neurological diseases, particularly in cerebral ischemic and hemorrhagic stroke. Additionally, STAT3 has also been reported to play a critical role in neuroprotective therapies. In light of the pleiotropic effects of STAT3 on the nervous system, we present the elaborate network of roles that STAT3 plays in cerebral ischemia and hemorrhage in this review. First, we introduce basic knowledge regarding STAT3 and briefly summarize the activation, inactivation, and regulation of the STAT3 pathway. Next, we describe the activation of STAT3 following cerebral ischemia and hemorrhage. Subsequently, we discuss the physiopathological roles of STAT3 in cerebral ischemia and hemorrhage. Moreover, we summarize several significant cerebral ischemic and hemorrhagic stroke treatments that target the STAT3 signaling pathway, including pharmacological and physical therapies. Finally, we highlight research progress on STAT3 in stroke. This review presents the important roles of STAT3 in the nervous system and may contribute to the promotion of STAT3 as a new therapeutic target.
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