Preoperative prediction power of radiomics and non-radiomics methods based on MRI for early recurrence in hepatocellular carcinoma: a systemic review and meta-analysis.

OBJECTIVE: To compare radiomics and non-radiomics in predicting early recurrence (ER) in patients with hepatocellular carcinoma (HCC) after curative surgery. METHODS: We systematically searched PubMed and Embase databases. Studies with clear reference criteria were selected. Data were extracted and assessed for quality using the quality in prognosis studies tool (QUIPS) by two independent authors. All included radiomics studies underwent radiomics quality score (RQS) assessment. We calculated sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) using random or fixed models with a 95%CI. Forest maps visualized the data, and summary receiver operating characteristic (sROC) curves with the area under the curve (AUC) were generated. Meta-regression and subgroup analyses explored sources of heterogeneity. We compared sensitivity, specificity, PLR, and NLR using the z-test and compared AUC values using the Delong test. RESULTS: Our meta-analysis included 10 studies comprising 1857 patients. For radiomics, the pooled sensitivity, specificity, AUC of sROC, PLR and NLR were 0.84(95%CI: 0.78-0.89), 0.80(95%CI: 0.75-0.85), 0.89(95%CI: 0.86-0.91), 4.28(95%CI: 3.48-5.27) and 0.20(95%CI: 0.14-0.27), respectively, but with significant heterogeneity (I2 = 60.78% for sensitivity, I2 = 55.79% for specificity) and potential publication bias (P = 0.04). The pooled sensitivity, specificity, AUC of sROC, PLR, NLR for non-radiomics were 0.75(95%CI:0.68-0.81), 0.78(95%CI:0.72-0.83), 0.83(95%CI: 0.80-0.86), 3.45(95%CI: 2.68-4.44) and 0.32(95%CI: 0.24-0.41), respectively. There was no significant heterogeneity in this group (I2 = 0% for sensitivity, I2 = 17.27% for specificity). Radiomics showed higher diagnostic accuracy (AUC: 0.89 vs. 0.83, P = 0.0456), higher sensitivity (0.84 vs. 0.75, P = 0.0385) and lower NLR (0.20 vs. 0.32, P = 0.0287). CONCLUSION: The radiomics from preoperative MRI effectively predicts ER of HCC and has higher diagnostic accuracy than non-radiomics. Due to potential publication bias and suboptimal RQS scores in radiomics, these results should be interpreted cautiously.

Genetically determined blood pressure, antihypertensive drug classes, and frailty: A Mendelian randomization study.

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One-sample Mendelian randomization (MR) and summary data-based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one-sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65-0.90; p = 0.001) and CCB use (0.83; 0.72-0.95; p = 0.007), equivalent to a 10-mm Hg reduction in systolic BP, was significantly associated with lower risk of pre-frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39-1.33; p = 0.296) or thiazides variants (0.74; 0.53-1.03; p = 0.072) on pre-frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta -0.02, p = 2.87 × 10-4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty.

The Role of Astrocytes in Migraine with Cortical Spreading Depression: Protagonists or Bystanders? A Narrative Review.

Cortical spreading depression (CSD) is a slow wave of cortical depolarization closely associated with migraines with an aura. Previously, it was thought that CSD depolarization was mainly driven by neurons, with characteristic changes in neuronal swelling and increased extracellular potassium (K+) and glutamate. However, the role of astrocytes, a member of the neurovascular unit, in migraine with CSD has recently received increasing attention. In the early stages of CSD, astrocytes provide neurons with energy support and clear K+ and glutamate from synaptic gaps. However, in the late stages of CSD, astrocytes release large amounts of lactic acid to exacerbate hypoxia when the energy demand exceeds the astrocytes' compensatory capacity. Astrocyte endfoot swelling is a characteristic of CSD, and neurons are not similarly altered. It is primarily due to K+ influx and abnormally active calcium (Ca2+) signaling. Aquaporin 4 (AQP-4) only mediates K+ influx and has little role as an aquaporin. Astrocytes endfoot swelling causes perivascular space closure, slowing the glymphatic system flow and exacerbating neuroinflammation, leading to persistent CSD. Astrocytes are double-edged swords in migraine with CSD and may be potential targets for CSD interventions.

Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis.

BACKGROUND: Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM: To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS: 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS: Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION: Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

CRISPR/Cas9-mediated editing of GmDWF1 brassinosteroid biosynthetic gene induces dwarfism in soybean.

KEY MESSAGE: The study on the GmDWF1-deficient mutant dwf1 showed that GmDWF1 plays a crucial role in determining soybean plant height and yield by influencing the biosynthesis of brassinosteroids. Soybean has not adopted the Green Revolution, such as reduced height for increased planting density, which have proven beneficial for cereal crops. Our research identified the soybean genes GmDWF1a and GmDWF1b, homologous to Arabidopsis AtDWF1, and found that they are widely expressed, especially in leaves, and linked to the cellular transport system, predominantly within the endoplasmic reticulum and intracellular vesicles. These genes are essential for the synthesis of brassinosteroids (BR). Single mutants of GmDWF1a and GmDWF1b, as well as double mutants of both genes generated through CRISPR/Cas9 genome editing, exhibit a dwarf phenotype. The single-gene mutant exhibits moderate dwarfism, while the double mutant shows more pronounced dwarfism. Despite the reduced stature, all types of mutants preserve their node count. Notably, field tests have shown that the single GmDWF1a mutant produced significantly more pods than wild-type plants. Spraying exogenous brassinolide (BL) can compensate for the loss in plant height induced by the decrease in endogenous BRs. Comparing transcriptome analyses of the GmDWF1a mutant and wild-type plants revealed a significant impact on the expression of many genes that influence soybean growth. Identifying the GmDWF1a and GmDWF1b genes could aid in the development of compact, densely planted soybean varieties, potentially boosting productivity.

Opportunities and perspectives of small molecular phosphodiesterase inhibitors in neurodegenerative diseases.

Phosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy. From this point of view, PDE inhibition will provide a promising therapeutic strategy for treating neurodegenerative disorders. Herein, we summarized the PDE inhibitors that have entered the clinical trials or been discovered in recent five years. Well-designed clinical or preclinical investigations have confirmed the effectiveness of PDE inhibitors, such as decreasing Aß oligomerization and tau phosphorylation, alleviating neuro-inflammation and oxidative stress, modulating neuronal plasticity and improving long-term cognitive impairment.

The Diagnostic Accuracy Between Radiomics Model and Non-radiomics Model for Preoperative of Microvascular Invasion of Solitary Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: Microvascular invasion (MVI) is a key prognostic factor for hepatocellular carcinoma (HCC). The predictive models for solitary HCC could potentially integrate more comprehensive tumor information. Owing to the diverse findings across studies, we aimed to compare radiomic and non-radiomic methods for preoperative MVI detection in solitary HCC. MATERIALS AND METHODS: Articles were reviewed from databases including PubMed, Embase, Web of Science, and the Cochrane Library until April 7, 2023. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model within a 95% confidence interval (CI). Diagnostic accuracy was assessed using summary receiver-operating characteristic curves and the area under the curve (AUC). Meta-regression and Z-tests identified heterogeneity and compared the predictive accuracy. Subgroup analyses were performed to compare the AUC of two methods according to study type, study design, tumor size, modeling methods, and imaging modality. RESULTS: The analysis incorporated 26 studies involving 3539 patients with solitary HCC. The radiomics models showed a pooled sensitivity and specificity of 0.79 (95%CI: 0.72-0.85) and 0.78 (95%CI: 0.73-0.82), with an AUC at 0.85 (95%CI: 0.82-0.88). Conversely, the non-radiomics models had sensitivity and specificity of 0.74 (95%CI: 0.65-0.81) and 0.88 (95%CI: 0.82-0.92) and an AUC of 0.88 (95%CI: 0.85-0.91). Subgroups with preoperative MRI, larger tumors, and functional imaging had higher accuracy than those using preoperative CT, smaller tumors, and conventional imaging. CONCLUSION: Non-radiomic methods outperformed radiomic methods, but high heterogeneity calls across studies for cautious interpretation.

The critical role of residues Phe120 and Val161 of (2 R,3 R)­2,3­butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site-directed mutagenesis.

NAD+-dependent (2 R,3 R)­2,3­butanediol dehydrogenase (BDH) from Neisseria gonorrhoeae (NgBDH) is a representative member of the medium-chain dehydrogenase/reductase (MDR) superfamily. To date, little information is available on the substrate binding sites and catalytic residues of BDHs from this superfamily. In this work, according to molecular docking studies, we found that conserved residues Phe120 and Val161 form strong hydrophobic interactions with both (2 R,3 R)­2,3­butanediol (RR-BD) and meso-2,3­butanediol (meso-BD) and that mutations of these residues to alanine or threonine impair substrate binding. To further evaluate the roles of these two residues, Phe120 and Val161 were mutated to alanine or threonine. Kinetic analysis revealed that, relative to those of wild type, the apparent KM values of the Phe120Ala mutant for RR-BD and meso-BD increased 36- and 369-fold, respectively; the catalytic efficiencies of this mutant with RR-BD and meso-BD decreased approximately 586- and 3528-fold, respectively; and the apparent KM values of the Val161Ala mutant for RR-BD and meso-BD increased 4- and 37-fold, respectively, the catalytic efficiencies of this mutant with RR-BD and meso-BD decreased approximately 3- and 28-fold, respectively. Additionally, the Val161Thr mutant slightly decreased catalytic efficiencies (twofold with RR-BD; 7.3-fold with meso-BD) due to an increase in KM (sixfold for RR-BD; 24-fold for meso-BD) and a slight increase (2.8-fold with RR-BD; 3.3-fold with meso-BD) in kcat. These findings validate the critical roles of Phe120 and Val161 of NgBDH in substrate binding and catalysis. Overall, the current study provides a better understanding of the substrate binding and catalysis of BDHs within the MDR superfamily.

Evolution of the FLOWERING LOCUS T-like genes in angiosperms: a core-Lamiales-specific diversification.

Plant life-history is determined by two transitions, the germination and the flowering times, in which the phosphatidylethanolamine-binding proteins (PEBP) FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) play key regulatory roles. Compared to the highly conserved TFL1-likes, FT-like genes vary in copy numbers significantly in gymnosperms and monocots of the angiosperms, while sporadic duplications can be observed in eudicots. Here, via a systematic analysis of the PEBPs in angiosperms with a special focus on twelve representative species featuring high-quality genomes in the Lamiales order, we identified a successive lineage-specific but systematic expansion of FT-like genes in the families of core Lamiales. The first expansion event generated FT1-likes mainly via a core-Lamiales-specific whole-genome-duplication (cL-WGD), while on the other hand, a likely random duplication produced the FT2-likes in the lineages containing Scrophulariaceae and rest of the core Lamiales. Both FT1- and FT2-like genes were further amplified tandemly in some families. These expanded FT-likes featured highly diverged expression patterns and structural variation, indicating functional diversification. Intriguingly, some core Lamiales contained the relict MOTHER OF FT AND TFL1 like 2 (MFT2) that likely expanded in the common ancestor of angiosperms. Our data showcase the highly dynamic lineage-specific expansion of the FT-like genes, thus provide important and fresh evolutionary insights into the gene-regulatory-network underpinning flowering time diversity in Lamiales, and more generally, in angiosperms.

A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Desmoglein 2 and desmocollin 2 depletions promote malignancy through distinct mechanisms in triple-negative and luminal breast cancer.

BACKGROUND: Aberrant expressions of desmoglein 2 (Dsg2) and desmocollin 2(Dsc2), the two most widely distributed desmosomal cadherins, have been found to play various roles in cancer in a context-dependent manner. Their specific roles on breast cancer (BC) and the potential mechanisms remain unclear. METHODS: The expressions of Dsg2 and Dsc2 in human BC tissues and cell lines were assessed by using bioinformatics analysis, immunohistochemistry and western blotting assays. Wound-healing and Transwell assays were performed to evaluate the cells' migration and invasion abilities. Plate colony-forming and MTT assays were used to examine the cells' capacity of proliferation. Mechanically, Dsg2 and Dsc2 knockdown-induced malignant behaviors were elucidated using western blotting assay as well as three inhibitors including MK2206 for AKT, PD98059 for ERK, and XAV-939 for ß-catenin. RESULTS: We found reduced expressions of Dsg2 and Dsc2 in human BC tissues and cell lines compared to normal counterparts. Furthermore, shRNA-mediated downregulation of Dsg2 and Dsc2 could significantly enhance cell proliferation, migration and invasion in triple-negative MDA-MB-231 and luminal MCF-7 BC cells. Mechanistically, EGFR activity was decreased but downstream AKT and ERK pathways were both activated maybe through other activated protein tyrosine kinases in shDsg2 and shDsc2 MDA-MB-231 cells since protein tyrosine kinases are key drivers of triple-negative BC survival. Additionally, AKT inhibitor treatment displayed much stronger capacity to abolish shDsg2 and shDsc2 induced progression compared to ERK inhibition, which was due to feedback activation of AKT pathway induced by ERK inhibition. In contrast, all of EGFR, AKT and ERK activities were attenuated, whereas ß-catenin was accumulated in shDsg2 and shDsc2 MCF-7 cells. These results indicate that EGFR-targeted therapy is not a good choice for BC patients with low Dsg2 or Dsc2 expression. Comparatively, AKT inhibitors may be more helpful to triple-negative BC patients with low Dsg2 or Dsc2 expression, while therapies targeting ß-catenin can be considered for luminal BC patients with low Dsg2 or Dsc2 expression. CONCLUSION: Our finding demonstrate that single knockdown of Dsg2 or Dsc2 could promote proliferation, motility and invasion in triple-negative MDA-MB-231 and luminal MCF-7 cells. Nevertheless, the underlying mechanisms were cellular context-specific and distinct.

Associations of birth weight, plasma metabolome in adulthood and risk of type 2 diabetes.

AIMS: We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. MATERIALS AND METHODS: A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. RESULTS: Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: -0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large-sized very low-density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls. CONCLUSIONS: We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk.

MB16 - (M=Sc, Y, La): Perfect Bowl-Like Boron Clusters.

The introduction of transition-metal doping has engendered a remarkable array of unprecedented boron motifs characterized by distinctive geometries and bonding, particularly those heretofore unobserved in pure boron clusters. In this study, we present a perfect (no defects) boron framework manifesting an inherently high-symmetry, bowl-like architecture, denoted as MB16 - (M=Sc, Y, La). In MB16 -, the B16 is coordinated to M atoms along the C5v-symmetry axis. The bowl-shaped MB16 - structure is predicted to be the lowest-energy structure with superior stability, owing to its concentric (2 π+10 π) dual π aromaticity. Notably, the C5v-symmetry bowl-like B16 - is profoundly stabilized through the doping of an M atom, facilitated by strong d-pπ interactions between M and boron motifs, in conjunction with additional electrostatic stabilization by an electron transfer from M to the boron motifs. This concerted interplay of covalent and electrostatic interactions between M and bowl-like B16 renders MB16 - a species of exceptional thermodynamic stability, thus making it a viable candidate for gas-phase experimental detection.

Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity.

The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

Bioengineering Full-scale auricles using 3D-printed external scaffolds and decellularized cartilage xenograft.

Reconstruction of the human auricle remains a formidable challenge for plastic surgeons. Autologous costal cartilage grafts and alloplastic implants are technically challenging, and aesthetic and/or tactile outcomes are frequently suboptimal. Using a small animal "bioreactor", we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimics the size, shape, and biomechanical properties of the native human auricle. The full-scale polylactic acid ear scaffolds were 3D-printed based upon data acquired from 3D photogrammetry of an adult ear. Ovine costal cartilage was processed either through mincing (1 mm3) or zesting (< 0.5 mm3), and then fully decellularized and sterilized. At explantation, both the minced and zested neoears maintained the size and contour complexities of the scaffold topography with steady tissue ingrowth through 6 months in vivo. A mild inflammatory infiltrate at 3 months was replaced by homogenous fibrovascular tissue ingrowth enveloping individual cartilage pieces at 6 months. All ear constructs were pliable, and the elasticity was confirmed by biomechanical analysis. Longer-term studies of the neoears with faster degrading biomaterials will be warranted for future clinical application. STATEMENT OF SIGNIFICANCE: Accurate reconstruction of the human auricle has always been a formidable challenge to plastic surgeons. In this article, we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimic the size, shape, and biomechanical properties of the native human auricle. Longer-term studies of the neoears with faster degrading biomaterials will be warranted for future clinical application.

Enhancing Iodine Capture of Porous Organic Cages through N-Heteroatom Engineering.

Iodine radioisotopes, produced or released during nuclear-related activities, severely affect human health and the environment. The efficient removal of radioiodine from both aqueous and vapor phases is crucial for the sustainable development of nuclear energy. In this study, we propose an "N-heteroatom engineering" strategy to design three porous organic cages with N-containing functional groups for efficient iodine capture. Among the molecular cages investigated, FT-Cage incorporating tertiary amine groups and RT-Cage with secondary amine groups show higher adsorption capacity and much faster iodine release compared to IT-Cage with imine groups. Detailed investigations demonstrate the superiority of amine groups, along with the influence of crystal structures and porosity, for iodine capture. These findings provide valuable insights for the design of porous organic cages with enhanced capabilities for capturing iodine.

Molecular and genetic regulation of petal number variation in plants.

Floral forms with an increased number of petals, also known as double flower (DF) with great agronomic and economic values, have been selected and conserved in many domesticated plants, particularly in ornamentals. The molecular and genetic mechanisms that control this trait are therefore a hot topic, not only for scientists, but also for breeders. In this review, we summarize the current knowledge on the gene regulatory networks of flower initiation and development and known mutations that lead to variation of petal number in many species. Besides the well-accepted miR172/AP2-like module, for which many questions remain unanswered, we also discuss the current knowledge of other pathways in which mutations also lead to extra-petals formation, such as those involved in meristem development, hormones signaling, epigenetic regulations, and responses to environmental signals. We discuss how the concept of "natural mutants" and the recent advances in genomics and genome editing makes it possible to explore the molecular mechanisms underlying the DF formation, and how such knowledge could contribute to the future breeding and selection of this trait in more crops.

Comprehensive exercise reduces traumatic brain injury deficits via improving the neural network function of hippocampal CA1 and medial entorhinal cortex.

The present study aimed to investigate the alterations in functional interaction between hippocampal CA1 and medial entorhinal cortex (MEC) after moderate traumatic brain injury (TBI) in C57BL/6J mice, and the possible beneficial effects of comprehensive exercise (CE). Following TBI, two microelectrodes were implanted into CA1 and MEC for extracellular recording. We found a clear synchronization of neuronal firing in CA1 and MEC, particularly within 100 Hz and peaked at 20-30 Hz range. TBI induced a significant reduction (P < 0.001) of the coherences of firing between 20-40 Hz frequency band. The mean power spectral densities (PSD) of all group mice in MEC were steadily larger than the values in CA1 in both 20-40 Hz and 56-100 Hz ranges. TBI induced significant and consistent increases of averaged 20-40 Hz or 56-100 Hz PSD (P < 0.001 or P < 0.01) in both CA1 and MEC. Injured mice displayed more varied firing patterns, and showed increased burst frequency (BF), burst duration (BD), inter-spike intervals (ISI) and inter-burst interval (IBI). Injured mice also showed worsened neurological function, sleep, gait performance, and working memory. CE facilitated the restoration of aforementioned electrophysiological characteristics and functional deficits in TBI mice. These results suggest that the beneficial effects of CE on TBI functional deficits may be partly attributed to improved neuronal network interaction between CA1 and MEC.

Causal role of the frontal eye field in attention-induced ocular dominance plasticity.

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the 'dichoptic-backward-movie' adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.