Immunity to pathogenic fungi in the eye.

Fusarium, Aspergillus and Candida are important fungal pathogens that cause visual impairment and blindness in the USA and worldwide. This review will summarize the epidemiology and clinical features of corneal infections and discuss the immune and inflammatory responses that play an important role in clinical disease. In addition, we describe fungal virulence factors that are required for survival in infected corneas, and the activities of neutrophils in fungal killing, tissue damage and cytokine production.

Rapid and Repeated Climate Adaptation Involving Chromosome Inversions following Invasion of an Insect.

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.

Correction: FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by silencing a glycosyl hydrolase coding gene expression.

[This corrects the article DOI: 10.1371/journal.ppat.1010157.].

Kynurenine 3-monooxygenase limits de novo NAD+ synthesis through dietary tryptophan in renal proximal tubule epithelial cell models.

Nicotinamide adenine dinucleotide (NAD+) is a pivotal coenzyme, essential for cellular reactions, metabolism, and mitochondrial function. Depletion of kidney NAD+ levels and reduced de novo NAD+ synthesis through the tryptophan-kynurenine pathway are linked to acute kidney injury (AKI), whereas augmenting NAD+ shows promise in reducing AKI. We investigated de novo NAD+ biosynthesis using in vitro, ex vivo, and in vivo models to understand its role in AKI. Two-dimensional (2-D) cultures of human primary renal proximal tubule epithelial cells (RPTECs) and HK-2 cells showed limited de novo NAD+ synthesis, likely due to low pathway enzyme gene expression. Using three-dimensional (3-D) spheroid culture model improved the expression of tubular-specific markers and enzymes involved in de novo NAD+ synthesis. However, de novo NAD+ synthesis remained elusive in the 3-D spheroid culture, regardless of injury conditions. Further investigation revealed that 3-D cultured cells could not metabolize tryptophan (Trp) beyond kynurenine (KYN). Intriguingly, supplementation of 3-hydroxyanthranilic acid into RPTEC spheroids was readily incorporated into NAD+. In a human precision-cut kidney slice (PCKS) ex vivo model, de novo NAD+ synthesis was limited due to substantially downregulated kynurenine 3-monooxygenase (KMO), which is responsible for KYN to 3-hydroxykynurenine conversion. KMO overexpression in RPTEC 3-D spheroids successfully reinstated de novo NAD+ synthesis from Trp. In addition, in vivo study demonstrated that de novo NAD+ synthesis is intact in the kidney of the healthy adult mice. Our findings highlight disrupted tryptophan-kynurenine NAD+ synthesis in in vitro cellular models and an ex vivo kidney model, primarily attributed to KMO downregulation.NEW & NOTEWORTHY Nicotinamide adenine dinucleotide (NAD+) is essential in regulating mitochondrial function. Reduced NAD+ synthesis through the de novo pathway is associated with acute kidney injury (AKI). Our study reveals a disruption in de novo NAD+ synthesis in proximal tubular models, but not in vivo, attributed to downregulation of enzyme kynurenine 3-monooxygenase (KMO). These findings highlight a crucial role of KMO in governing de novo NAD+ biosynthesis within the kidney, shedding light on potential AKI interventions.

FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by silencing a glycosyl hydrolase coding gene expression.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression primarily found in plants and animals. Fungi produce microRNA-like RNAs (milRNAs) that are structurally similar to miRNAs and functionally important in various biological processes. The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Banana Fusarium vascular wilt that threatens global banana production. It remains uncharacterized about the biosynthesis and functions of milRNAs in Foc. In this study, we investigated the biological function of milRNAs contributing to Foc pathogenesis. Within 24 hours post infecting the host, the Argonaute coding gene FoQDE2, and two Dicer coding genes FoDCL1 and FoDCL2, all of which are involved in milRNA biosynthesis, were significantly induced. FoQDE2 deletion mutant exhibited decreased virulence, suggesting the involvement of milRNA biosynthesis in the Foc pathogenesis. By small RNA sequencing, we identified 364 small RNA-producing loci in the Foc genome, 25 of which were significantly down-regulated in the FoQDE2 deletion mutant, from which milR-87 was verified as a FoQDE2-depedent milRNA based on qRT-PCR and Northern blot analysis. Compared to the wild-type, the deletion mutant of milR-87 was significantly reduced in virulence, while overexpression of milR-87 enhanced disease severity, confirming that milR-87 is crucial for Foc virulence in the infection process. We furthermore identified FOIG_15013 (a glycosyl hydrolase-coding gene) as the direct target of milR-87 based on the expression of FOIG_15013-GFP fusion protein. The FOIG_15013 deletion mutant displayed similar phenotypes as the overexpression of milR-87, with a dramatic increase in the growth, conidiation and virulence. Transient expression of FOIG_15013 in Nicotiana benthamiana leaves activates the host defense responses. Collectively, this study documents the involvement of milRNAs in the manifestation of the devastating fungal disease in banana, and demonstrates the importance of milRNAs in the pathogenesis and other biological processes. Further analyses of the biosynthesis and expression regulation of fungal milRNAs may offer a novel strategy to combat devastating fungal diseases.

Topotactic Conversion of Titanium-Oxo Clusters to a Stable TOC-Based Metal-Organic Framework with the Selective Adsorption of Cationic Dyes.

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

Functional brain network alterations in the co-occurrence of autism spectrum disorder and attention deficit hyperactivity disorder.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two highly prevalent and commonly co-occurring neurodevelopmental disorders. The neural mechanisms underpinning the comorbidity of ASD and ADHD (ASD + ADHD) remain unclear. We focused on the topological organization and functional connectivity of brain networks in ASD + ADHD patients versus ASD patients without ADHD (ASD-only). Resting-state functional magnetic resonance imaging (rs-fMRI) data from 114 ASD and 161 typically developing (TD) individuals were obtained from the Autism Brain Imaging Data Exchange II. The ASD patients comprised 40 ASD + ADHD and 74 ASD-only individuals. We constructed functional brain networks for each group and performed graph-theory and network-based statistic (NBS) analyses. Group differences between ASD + ADHD and ASD-only were analyzed at three levels: nodal, global, and connectivity. At the nodal level, ASD + ADHD exhibited topological disorganization in the temporal and occipital regions, compared with ASD-only. At the global level, ASD + ADHD and ASD-only displayed no significant differences. At the connectivity level, the NBS analysis revealed that ASD + ADHD showed enhanced functional connectivity between the prefrontal and frontoparietal regions, as well as between the orbitofrontal and occipital regions, compared with ASD-only. The hippocampus was the shared region in aberrant functional connectivity patterns in ASD + ADHD and ASD-only compared with TD. These findings suggests that ASD + ADHD displays altered topology and functional connectivity in the brain regions that undertake social cognition, language processing, and sensory processing.

Dosimetric validation for prospective clinical trial on GRID collimator-based spatially fractionated radiation therapy: Dose metrics consistency and heterogeneous pattern reproducibility.

PURPOSE: The purpose of this study is to characterize the dosimetric properties of a commercial brass GRID collimator for high energy photon beams including 15 and 10 MV. Then, the difference in dosimetric parameters of GRID beams among different energies and linacs was evaluated. METHOD: A water tank scanning system was used to acquire the dosimetric parameters, including the percentage depth dose (PDD), beam profiles, peak to valley dose ratios (PVDRs), and output factors (OFs). The profiles at various depths were measured at 100 cm source to surface distance (SSD), and field sizes of 10 × 10 cm2 and 20 × 20 cm2 on three linacs. The PVDRs and OFs were measured and compared with the treatment planning system (TPS) calculations. RESULTS: Compared with the open beam data, there were noticeable changes in PDDs of GRID fields across all the energies. The GRID fields demonstrated a maximal of 3 mm shift in dmax (Truebeam STX, 15MV, 10 × 10 cm2). The PVDR decreased as beam energy increases. The difference in PVDRs between Trilogy and Truebeam STx using 6MV and 15MV was 1.5% ± 4.0% and 2.1% ± 4.3%, respectively. However, two Truebeam linacs demonstrated less than 2% difference in PVDRs. The OF of the GRID field was dependent on the energy and field size. The measured PDDs, PVDRs, and OFs agreed with the TPS calculations within 3% difference. The TPS calculations agreed with the measurements when using 1 mm calculation resolution. CONCLUSION: The dosimetric characteristics of high-energy GRID fields, especially PVDR, significantly differ from those of low-energy GRID fields. Two Truebeam machines are interchangeable for GRID therapy, while a pronounced difference was observed between Truebeam and Trilogy. A series of empirical equations and reference look-up tables for GRID therapy can be generated to facilitate clinical applications.

Genome Sequence Resource of Fusarium graminearum TaB10 and Fusarium avenaceum KA13, Causal Agents of Stored Apple Rot.

The filamentous fungus Fusarium graminearum is a well-known cereal pathogen and F. avenaceum is a pathogen with a wide host range. Recently, both species were reported as causal agents of apple rot, raising concerns about postharvest yield losses and mycotoxin contamination. Here, we report genome assemblies of F. avenaceum KA13 and F. graminearum TaB10, both isolated from fruits with symptoms of apple rot. The final F. avenaceum KA13 genome sequence assembly of 41.7 Mb consists of 34 scaffolds, with an N50 value of 2.2 Mb and 15,886 predicted genes. The total size of the final F. graminearum TaB10 assembly is 36.76 Mb, consisting of 54 scaffolds with an N50 value of 1.7 Mb, and it consists of 14,132 predicted genes. These new genomes provide valuable resources to better understand plant-microbe interaction in stored apple rot disease. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Differential Colonization of the Plant Vasculature Between Endophytic Versus Pathogenic Fusarium oxysporum Strains.

Plant xylem colonization is the hallmark of vascular wilt diseases caused by phytopathogens within the Fusarium oxysporum species complex. Recently, xylem colonization has also been reported among endophytic F. oxysporum strains, resulting in some uncertainty. This study compares xylem colonization processes by pathogenic versus endophytic strains in Arabidopsis thaliana and Solanum lycopersicum, using Arabidopsis pathogen Fo5176, tomato pathogen Fol4287, and the endophyte Fo47, which can colonize both plant hosts. We observed that all strains were able to advance from epidermis to endodermis within 3 days postinoculation (dpi) and reached the root xylem at 4 dpi. However, this shared progression was restricted to lateral roots and the elongation zone of the primary root. Only pathogens reached the xylem above the primary-root maturation zone (PMZ). Related to the distinct colonization patterns, we also observed stronger induction of callose at the PMZ and lignin deposition at primary-lateral root junctions by the endophyte in both plants. This observation was further supported by stronger induction of Arabidopsis genes involved in callose and lignin biosynthesis during the endophytic colonization (Fo47) compared with the pathogenic interaction (Fo5176). Moreover, both pathogens encode more plant cell wall-degrading enzymes than the endophyte Fo47. Therefore, observed differences in callose and lignin deposition could be the combination of host production and the subsequent fungal degradation. In summary, this study demonstrates spatial differences between endophytic and pathogenic colonization, strongly suggesting that further investigations of molecular arm-races are needed to understand how plants differentiate friend from foe. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Low-Dose Erythropoietin Amplifies Beneficial Effects of Angiotensin II Blockade on Glomerulosclerosis.

Exogenous erythropoietin (EPO) is used to treat anemia in patients with chronic kidney disease (CKD). Concerns about the possible adverse effect of EPO on the progression of CKD have been raised owing to nonerythroid cell effects. We investigated the effects of low-dose EPO, independent of correcting anemia, on existing glomerulosclerosis. Adult mice underwent 5/6 nephrectomy and were randomized into the following 4 groups at week 8 after surgery: vehicle (VEH), losartan (angiotensin II type 1 receptor blocker [ARB]), darbepoetin-α (DA), or combination (DA+ARB). Four weeks later, mice were euthanized, followed by evaluation of renal structure and function. Glomerular endothelial cells and podocytes were cultured to evaluate the effects of DA on cell migration, apoptosis, and Akt signaling. ARB reduced blood pressure, albuminuria, and the level of serum creatinine and increased hematocrit compared with VEH, whereas low-dose DA only reduced the level of serum creatinine. Combination treatment showed a trend to increase hematocrit and survival compared with ARB alone. Combination treatment but not ARB alone significantly reduced the progression of glomerulosclerosis compared with VEH. Low-dose DA resulted in more preserved glomerular and peritubular capillary endothelial cells with increased p-Akt and even further endothelial cell preservation in combination with ARB. In cultured glomerular endothelial cells, angiotensin II induced more apoptosis, reduced migration, and decreased p-Flk1, a receptor for the proangiogenic vascular endothelial growth factor. DA counteracted these injuries and increased p-Akt, a key factor in angiogenesis and cell survival. DA also protected cultured podocytes against transforming growth factor ß-induced apoptosis and synaptopodin loss. Low-dose EPO directly protects glomerular and peritubular endothelial cells via Akt phosphorylation. Therefore, treatment using a combination of low-dose EPO and ARB results in less progression of glomerulosclerosis in an experimental CKD model.

Near-Infrared Fluorescent Probe for the In Situ Visualization of Oxidative Stress in the Brains of Neuroinflammatory and Schizophrenic Mice.

Schizophrenia is a common mental disorder with unclear mechanisms. Oxidative stress and neuroinflammation play important roles in the pathological process of schizophrenia. Superoxide anion (O2•-) is an important oxidative stress biomarker in vivo. However, due to the existence of the blood-brain barrier (BBB), few near-infrared (NIR) fluorescent probes have been used for the sensing and detection of O2•- in the brain. With this research, we developed the first near-infrared fluorescent probe (named CT-CF3) for noninvasive detection of endogenous O2•- in the brain of mice. Enabling fluorescence monitoring of the dynamic changes in O2•- flux due to the prolonged activation of microglia in neuroinflamed and schizophrenic (SZ) mice brains, thereby providing direct evidence for the relationship between oxidative stress, neuroinflammation, and schizophrenia. Furthermore, we confirmed the O2•- burst in the brains of first-episode schizophrenic mice and assessed the effect of two atypical antipsychotic drugs (risperidone and olanzapine) on redox homeostasis.

RAD51C-RAD51D interplays with MSH5 and regulates crossover maturation in rice meiosis.

Meiotic crossovers ensure accurate chromosome segregation and increase genetic diversity. RAD51C and RAD51D play an early role in facilitating RAD51 during homologous recombination. However, their later function in meiosis is largely unknown in plants. Here, through targeted disruption of RAD51C and RAD51D, we generated three new mutants and revealed their later meiotic role in crossover maturation. The rad51c-3 and rad51d-4 mutants showed a mixture of bivalents and univalents and no chromosomal entanglements, whereas rad51d-5 exhibited an intermediate phenotype with reduced chromosomal entanglements and increased bivalent formation compared with knockout alleles. Comparisons of RAD51 loadings and chromosomal entanglements in these single mutants, rad51c-3 rad51d-4, rad51c-3 dmc1a dmc1b, and rad51d-4 dmc1a dmc1b suggest that the retained level of RAD51 in mutants is required for uncovering their function in crossover formation. Reductions in chiasma frequency and later HEI10 foci in these mutants support that crossover maturation requires RAD51C and RAD51D. Moreover, interaction between RAD51D and MSH5 indicates that RAD51 paralogs may cooperate with MSH5 to ensure accurate Holliday junction processing into crossover products. This finding of the role of RAD51 paralogs in crossover control may be conserved from mammals to plants and advances our current understanding of these proteins.

Testing for adaptive changes linked to range expansion following a single introduction of the fall webworm.

Adaptive evolution following colonization can affect the impact of invasive species. The fall webworm (FWW) invaded China 40 years ago through a single introduction event involving a severe bottleneck and subsequently diverged into two genetic groups. The well-recorded invasion history of FWW, coupled with a clear pattern of genetic divergence, provides an opportunity to investigate whether there is any sign of adaptive evolution following the invasion. Based on genome-wide SNPs, we identified genetically separated western and eastern groups of FWW and correlated spatial variation in SNPs with geographical and climatic factors. Geographical factors explained a similar proportion of the genetic variation across all populations compared with climatic factors. However, when the two population groups were analysed separately, environmental factors explained more variation than geographical factors. SNP outliers in populations of the western group had relatively stronger response to precipitation than temperature-related variables. Functional annotation of SNP outliers identified genes associated with insect cuticle protein potentially related to desiccation adaptation in the western group and genes associated with lipase biosynthesis potentially related to temperature adaptation in the eastern group. Our study suggests that invasive species may maintain the evolutionary potential to adapt to heterogeneous environments despite a single invasion event. The molecular data suggest that quantitative trait comparisons across environments would be worthwhile.

Optical metasurfaces for multiplex high-performance grating-type structural colors.

Optical metasurfaces provide a significant approach for the production of structural colors due to their excellent optical control abilities. Herein, we propose trapezoidal structural metasurfaces for achieving multiplex grating-type structural colors with high comprehensive performance originating from the anomalous reflection dispersion in the visible band. Single trapezoidal metasurfaces with different x-direction periods can tune the angular dispersion regularly from 0.036 rad/nm to 0.224 rad/nm to generate various structural colors, and composite trapezoidal metasurfaces with three kinds of combinations can achieve multiplex sets of structural colors. The brightness can be controlled by adjusting the distance between the trapezoids in a pair accurately. The designed structural colors have higher saturation than traditional pigmentary colors, whose excitation purity can reach 1.00. The gamut is about 158.1% of the Adobe RGB standard. This research has application potential in ultrafine displays, information encryption, optical storage, and anti-counterfeit tagging.

Redox-Active Two-Dimensional Tetrathiafulvalene-Copper Metal-Organic Framework with Boosted Electrochemical Performances for Supercapatteries.

Metal-organic frameworks (MOFs) have attracted noticeable attention as promising candidates for electrochemical energy storage. However, the lack of electrical conductivity and the weak stability of most MOFs result in poor electrochemical performances. Here, a tetrathiafulvalene (TTF)-based complex, formulated as [(CuCN)2(TTF(py)4)] (1) (TTF-(py)4 = tetra(4-pyridyl)-TTF), is assembled by in situ generation of coordinated CN- from a nontoxic source. Single-crystal X-ray diffraction analysis reveals that compound 1 possesses a two-dimensional layered planar structure, which is further stacked in parallel to form a three-dimensional supramolecular framework. The planar coordination environment of 1 is the first example of a TTF-based MOF. Attributed to the unique structure and redox TTF ligand, the electrical conductivity of 1 is significantly increased by 5 orders of magnitude upon iodine treatment. The iodine-treated 1 (1-ox) electrode displays typical battery-type behavior through electrochemical characterizations. The supercapattery based on the 1-ox positrode and AC negatrode presents a high specific capacity of 266.5 C g-1 at a specific current of 1 A g-1 with a remarkable specific energy of 62.9 Wh kg-1 at a specific power of 1.1 kW kg-1. The excellent electrochemical performance of 1-ox is one of the best among those reported supercapatteries, demonstrating a new strategy for developing MOF-based electrode materials.

The efficacy of schema therapy for personality disorders: a systematic review and meta-analysis.

OBJECTIVE: Personality disorders (PDs) are prevalent and associated with functional impairment and psychological disability. Studies suggest that schema therapy (ST) may be an effective treatment for PDs. This review aimed to evaluate the efficacy of ST in treating PDs. METHOD: We conducted a comprehensive literature search using PubMed, Embase, Web of Science, CENTRAL, PsycInfo, and Ovid Medline. We identified eight randomized controlled trials (587 participants) and seven single-group trials (163 participants). RESULTS: Meta-analyses revealed that ST had a moderate effect size (g = 0.359) compared to control conditions in reducing symptoms of PDs. Subgroup analysis indicated that the effect of ST on different types of PDs varied slightly, and that group ST (g = 0.859) was more effective than individual ST (g = 0.163) in treating PDs. Secondary outcome analysis revealed a moderate effect size (g = 0.256) for ST compared to control conditions in improving quality of life, and ST was found to reduce early maladaptive schema (g = 0.590). Single-group trials analysis showed that ST had a positive effect on PDs (OR = 0.241). CONCLUSION: ST appears to be an effective treatment for PDs, as it reduces symptoms and improves quality of life. This review provides support for the use of ST in the treatment of PDs.

New Degradable Semiconducting Polymers for Photoacoustic Imaging of λ-Carrageenan-Induced Arthritis Mouse Model.

Semiconducting polymer has a high extinction coefficient and a long band absorption and can be used as a photoacoustic imaging contrast agent. However, nonbiodegradable semiconducting polymers may cause biosafety issues due to being retained in the body. Therefore, developing degradable semiconducting polymers is necessary for in vivo imaging. Herein, we developed three degradable semiconducting polymers with unique optical properties. We adjusted the optical properties of semiconducting polymers by designing the molecular structure of semiconducting polymers. Polymers with a donor-π-acceptor structure could easily improve the optical properties through adjusting the donor or acceptor units. Through adjusting the electron-donor and -acceptor units, three diketopyrrolopyrrole derivative polymers (DPPTz, DPPQu, and DPPWu) were synthesized and converted into nanosize particles. By introducing the degradable chemical groups in the main chain structure of semiconducting polymers, diketopyrrolopyrrole polymers could be degraded by ClO-. Among these nanosize particles, DPPTz NPs and DPPQu NPs were used to achieve the in vivo photoacoustic imaging of λ-carrageenan-induced arthritis mouse model. This work provides a novel design idea for the designing of red-shifted semiconducting polymer with degradable properties.

Uncovering neural distinctions and commodities between two creativity subsets: A meta-analysis of fMRI studies in divergent thinking and insight using activation likelihood estimation.

The dual-process theory that two different systems of thought coexist in creative thinking has attracted considerable attention. In the field of creative thinking, divergent thinking (DT) is the ability to produce multiple solutions to open-ended problems in a short time. It is mainly considered an associative and fast process. Meanwhile, insight, the new and unexpected comprehension of close-ended problems, is frequently marked as a deliberate and time-consuming thinking process requiring concentrated effort. Previous research has been dedicated to revealing their separate neural mechanisms, while few studies have compared their differences and similarities at the brain level. Therefore, the current study applied Activation Likelihood Estimation to decipher common and distinctive neural pathways that potentially underlie DT and insight. We selected 27 DT studies and 30 insight studies for retrospective meta-analyses. Initially, two single analyses with follow-up contrast and conjunction analyses were performed. The single analyses showed that DT mainly involved the inferior parietal lobe (IPL), cuneus, and middle frontal gyrus (MFG), while the precentral gyrus, inferior frontal gyrus (IFG), parahippocampal gyrus (PG), amygdala (AMG), and superior parietal lobe were engaged in insight. Compared to insight, DT mainly led to greater activation in the IPL, the crucial part of the default mode network. However, insight caused more significant activation in regions related to executive control functions and emotional responses, such as the IFG, MFG, PG, and AMG. Notably, the conjunction analysis detected no overlapped areas between DT and insight. These neural findings implicate that various neurocognitive circuits may support DT and insight.

Treatment potential in APOL1-associated nephropathy.

PURPOSE OF REVIEW: More than 5 million African-Americans, and millions more in Africa and worldwide, possess apolipoprotein L1 gene (APOL1) high-risk genotypes with an increased risk for chronic kidney disease. This manuscript reviews treatment approaches for slowing the progression of APOL1-associated nephropathy. RECENT FINDINGS: Since the 2010 discovery of APOL1 as a cause of nondiabetic nephropathy in individuals with sub-Saharan African ancestry, it has become apparent that aggressive hypertension control, renin-angiotensin system blockade, steroids and conventional immunosuppressive agents are suboptimal treatments. In contrast, APOL1-mediated collapsing glomerulopathy due to interferon treatment and HIV infection, respectively, often resolve with cessation of interferon or antiretroviral therapy. Targeted therapies, including APOL1 small molecule inhibitors, APOL1 antisense oligonucleotides (ASO) and inhibitors of APOL1-associated inflammatory pathways, hold promise for these diseases. Evolving therapies and the need for clinical trials support the importance of increased use of APOL1 genotyping and kidney biopsy. SUMMARY: APOL1-associated nephropathy includes a group of related phenotypes that are driven by the same two genetic variants in APOL1. Clinical trials of small molecule inhibitors, ASO, and inflammatory pathway inhibitors may improve outcomes in patients with primary forms of APOL1-associated nephropathy.