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Abstract Background The evolutionally conserved homeobox transcription factor NKX2-5 has been at the forefront in the field of cardiac biology, providing molecular insights into the mechanisms of cardiac development and disease. This homodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). Mutations in the NKX2-5 gene have been linked to sporadic cases of congenital heart disease (CHD), making it a significant target for research and study. While several studies have been conducted on Caucasian populations, there is a dearth of knowledge on the effects of NKX2-5 gene mutations in other settings, underscoring the need for further investigation. Due to differences in geographical and ancestral origin, we hypothesize that mutations may vary across different populations. Understanding the genetic factors that cause CHD is essential for providing effective genetic counseling and developing strategies for risk reduction. Additionally, identification of NKX2-5 mutations in individuals with CHDs is crucial because patients with CHDs are at a higher risk of progressive conduction disease and sudden cardiac death, and genetic information is taken into consideration while making decisions regarding pacemakers and implantable cardiac defibrillators. To determine the risk of congenital heart disease among infants, we conducted a study where we sequenced the exon 1 and exon 2 of NKX 2.5 in patients with sporadic CHDs, with the aim of identifying mutations in the NKX2.5 gene. Results In this study, a novel frame-shift disease-causing mutation was discovered in patients with atrial-ventricular septal defect. The mutation, identified as c95_95 del A; cDNA.369–369 delA; g 369–369 delA, resulted in the substitution of phenylalanine to leucine (F295L), which in turn caused a truncated NKX2.5 protein. In addition, a non-synonymous mutation, g 316C > T; cDNA 316C > T leucine to arginine (L37R) substitution, was found in a patient with the tetralogy of Fallot, affecting protein function. Furthermore, a novel non-synonymous mutation identified as g 2295–2298; cDNA 755–758 delins AGGG, was predicted by mutation taster to be disease-causing in a ventricular septal defect. It is worth noting that none of these mutations were found among the control subjects, highlighting their potential significance in the pathogenesis of these cardiac defects. Conclusion Mutations in the NKX2.5 gene are associated with congenital heart diseases and provide molecular insight into the pathogenesis of congenital heart diseases. We recommend that patients with NKX2.5 mutations have periodic screening for cardiac conduction abnormalities and be evaluated for potential implanted cardiac defibrillators and pacemakers.

Deep sowing is a traditional method for drought resistance in maize production, and mesocotyl elongation is strongly associated with the ability of maize to germinate from deep soil. However, little is known about the functional genes and mechanisms regulating maize mesocotyl elongation. In the present study, we identified a plant‐specific SIMILAR TO RCD‐ONE (SRO) protein family member, ZmSRO1e, involved in maize mesocotyl elongation. The expression of ZmSRO1e is strongly inhibited upon transfer from dark to white light. The loss‐of‐function zmsro1e mutant exhibited a dramatically shorter mesocotyl than the wild‐type in both constant light and darkness, while overexpression of ZmSRO1e significantly promoted mesocotyl elongation, indicating that ZmSRO1e positively regulates mesocotyl elongation. We showed that ZmSRO1e physically interacted with ZmbZIP61, an ortholog of Arabidopsis ELONGATED HYPOCOTYL 5 (HY5) and showed a function similar to that of HY5 in regulating photomorphogenesis. We found that ZmSRO1e repressed the transcriptional activity of ZmbZIP61 toward target genes involved in the regulation of cell expansion, such as ZmEXPB4 and ZmEXPB6, by interfering with the binding of ZmbZIP61 to the promoters of target genes. Our results provide a new understanding of the mechanism by which SRO regulates photomorphogenesis and highlight its potential application in deep sowing‐resistant breeding. [ABSTRACT FROM AUTHOR]

Titanate photocatalysts with suitable cocatalysts are promising candidates for photocatalytic CO2 reduction, with the use of water as an electron donor. Here, several barium titanates with various compositions were examined, and BaTi4O9 (BT4) was found to be the best photocatalyst with the assistance of an Ag cocatalyst for photocatalytic CO2 reduction to form CO. The photocatalytic activity was further enhanced by the use of MnOx as an additional cocatalyst to construct an Ag-MnOx/BT4 photocatalyst, where Ag and MnOx were selectively deposited at different facets on BT4 crystal and functioned as active sites for CO2 reduction and water oxidation, respectively. As for the oxidative products from water, molecular oxygen (O2) and hydrogen peroxide (H2O2) were obtained. [ABSTRACT FROM AUTHOR]

Background: In neuroscience, accurately quantifying individual brain regions in large cohorts is a challenge. Differences in intracranial structures can suggest functional differences, but they also reflect the effects of other factors. However, there is currently no standardized method for the correction of intracranial structure measurements. Purpose: To identify the optimal method to counteract the influence of total intracranial volume (TIV) and gender on the measurement of intracranial structures. Study Type: Prospective. Population/Subjects: One hundred forty‐one healthy adult volunteers (70 male, mean age 21.8 ± 1.7 years). Field Strength/Sequence: T1‐weighted 3D gradient‐echo sequence at 3.0 T. Assessment: A radiologist with 5 years of work experience screened the raw images to exclude poor‐quality images. Freesurfer then performed automated segmentation to obtain measurements of intracranial structures. Male‐only, female‐only, and TIV‐matched sub‐samples were created separately. Comparisons between the original data and these sub‐samples were used to assess the effects of gender and TIV. Comparison the consistency between TIV‐matched sample and corrected data that corrected by four methods: Proportion method, power‐corrected proportion method, covariate regression method, and residual method. Statistical Tests: Cohen's d for examining group distribution disparities, t‐tests for probing mean differences, correlation coefficients to assess the relationships between intracranial substructure measurements and TIV. Multiple comparison corrections were applied to the results. Results: The correlation coefficients between TIV and the volumes of intracranial structures ranged from 0.033 to 0.883, with an average of 0.467. Thirty significant volume differences were found among 36 structures in the original sample, while no differences were observed in the TIV‐matched sample. Among the four correction methods, the residual method had highest consistency (similarity 94.4%) with the TIV‐matched group. Data Conclusion: The variation in intracranial structure sizes between genders was largely attributable to TIV. The residual method offers a more accurate and effective approach for correcting the effects of TIV on intracranial structures. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

A systematic study was conducted on the impact of annealing treatments on the microstructure and properties of cold-rolled Ti50Ni47Fe3 alloys using optical microscopy, scanning electron microscopy, electron backscattered diffraction, and an electronic universal testing machine. It was found that, during low-temperature annealing (400 °C and 500 °C), the annealing time had no significant effect on the microstructure or properties of the Ti50Ni47Fe3 alloy. Only elongation (δ) increased with the increase in the annealing time, and the grain orientation of the Ti50Ni47Fe3 alloy was <111>//RD (rolling direction). When annealing at medium–high temperature (600 °C), as the annealing time increased, recrystallization and grain growth processes occurred, resulting in a continuous decrease in strength and an increase in δ. Meanwhile, it was found that the grain orientation of the cold-rolled Ti50Ni47Fe3 alloy changed from <111>//RD during the recovery and recrystallization processes to <101>//RD after the grain growth process. The orientation distribution function cross-section φ2 = 45° results indicate that the texture was mainly distributed along the γ orientation line (φ1 = 0~90°, Φ = 54.7°, φ2 = 45°). When annealed at 400 °C and 500 °C, the texture of the Ti50Ni47Fe3 alloys was (111)[uvw]. When the annealing treatment was 600 °C for 120 min, a (110)[uvw] texture occurred. Additionally, ductile fracture occurred in all specimens, and the crack origin was located on one side of the fracture surface, with obvious "Y"-shaped propagation. This article studied annealing treatments of cold-rolled Ti50Ni47Fe3 alloys, providing corresponding theoretical guidance for subsequent production applications. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. Aims: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. Methods: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. Results: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. Conclusions: This review is distinguished by synthesizing cutting‐edge mechanisms linking inflammation to DPN and identifying innovative, inflammation‐targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

Dormancy is an adaptive trait which prevents seeds from germinating under unfavorable environmental conditions. Seeds with weak dormancy undergo pre‐harvest sprouting (PHS) which decreases grain yield and quality. Understanding the genetic mechanisms that regulate seed dormancy and resistance to PHS is crucial for ensuring global food security. In this study, we illustrated the function and molecular mechanism of TaSRO1 in the regulation of seed dormancy and PHS resistance by suppressing TaVP1. The tasro1 mutants exhibited strong seed dormancy and enhanced resistance to PHS, whereas the mutants of tavp1 displayed weak dormancy. Genetic evidence has shown that TaVP1 is epistatic to TaSRO1. Biochemical evidence has shown that TaSRO1 interacts with TaVP1 and represses the transcriptional activation of the PHS resistance genes TaPHS1 and TaSdr. Furthermore, TaSRO1 undermines the synergistic activation of TaVP1 and TaABI5 in PHS resistance genes. Finally, we highlight the great potential of tasro1 alleles for breeding elite wheat cultivars that are resistant to PHS. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains one of the top three causes of death. Currently, the only licensed vaccine against TB is the bacillus Calmette-Guerin (BCG), which lacks efficacy in preventing and controlling pulmonary TB in adults. We aimed to evaluate a nasal TB vaccine formulation composed of the Mtb-specific vaccine antigen ESAT-6, an Mtb-associated protein that can trigger protective immune responses, and S100A4, a recently characterized novel mucosal adjuvant. Mice were intranasally given recombinant ESAT-6 in the presence or absence of S100A4 as an adjuvant. We have provided experimental evidence demonstrating that S100A4 admixed to ESAT-6 could induce Mtb-specific adaptive immune responses after intranasal immunization. S100A4 remarkably augmented the levels of anti-ESAT-6 IgG in serum and IgA in mucosal sites, including lung exudates, bronchoalveolar lavage fluid (BALF) and nasal lavage. Furthermore, in both lung and spleen tissues, S100A4 strongly promoted ESAT-6-specific expansion of CD4 T cells. Both CD4 and CD8 T cells from these tissues expressed increased levels of IFN-γ, TNF-α, and IL-17, cytokines critical for antimicrobial activity. Antigen-reencounter-induced T cell proliferative responses, a key vaccine performance indicator, were augmented in the spleen of S100A4-adjuvanted mice. Furthermore, CD8 T cells from the spleen and lung tissues of these mice expressed higher levels of granzyme B upon antigen re-stimulation. S100A4-adjuvanted immunization may predict good mucosal protection against TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of "MCCA+jICA" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the "MCCA+jICA" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from "MCCA+jICA" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.