Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.

TANK-binding kinase 1 (TBK1) is a potential therapeutic target in multiple cancers, including clear cell renal cell carcinoma (ccRCC). However, targeting TBK1 in clinical practice is challenging. One approach to overcome this challenge would be to identify an upstream TBK1 regulator that could be targeted therapeutically in cancer specifically. In this study, we perform a kinome-wide small interfering RNA (siRNA) screen and identify doublecortin-like kinase 2 (DCLK2) as a TBK1 regulator in ccRCC. DCLK2 binds to and directly phosphorylates TBK1 on Ser172. Depletion of DCLK2 inhibits anchorage-independent colony growth and kidney tumorigenesis in orthotopic xenograft models. Conversely, overexpression of DCLK2203, a short isoform that predominates in ccRCC, promotes ccRCC cell growth and tumorigenesis in vivo. Mechanistically, DCLK2203 elicits its oncogenic signaling via TBK1 phosphorylation and activation. Taken together, these results suggest that DCLK2 is a TBK1 activator and potential therapeutic target for ccRCC.

Deep integration of metabolome and transcriptome characterizes alkaloid metabolism in Houttuynia cordata.

Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties.

Identification of the genetic characteristics of copy number variations in experimental specific pathogen-free ducks using whole-genome resequencing.

BACKGROUND: Specific pathogen-free ducks are a valuable laboratory resource for waterfowl disease research and poultry vaccine development. High throughput sequencing allows the systematic identification of structural variants in genomes. Copy number variation (CNV) can explain the variation of important duck genetic traits. Herein, the genome-wide CNVs of the three experimental duck species in China (Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)) were characterized using resequencing to determine their genetic characteristics and selection signatures. RESULTS: We obtained 4,810 CNV regions (CNVRs) by merging 73,012 CNVs, covering 4.2% of the duck genome. Functional analysis revealed that the shared CNVR-harbored genes were significantly enriched for 31 gene ontology terms and 16 Kyoto Encyclopedia of Genes and Genomes pathways (e.g., olfactory transduction and immune system). Based on the genome-wide fixation index for each CNVR, growth (SPAG17 and PTH1R), disease resistance (CATHL3 and DMBT1), and thermoregulation (TRPC4 and SLIT3) candidate genes were identified in strongly selected signatures specific to JD, SM, and SX, respectively. CONCLUSIONS: In conclusion, we investigated the genome-wide distribution of experimental duck CNVs, providing a reference to establish the genetic basis of different phenotypic traits, thus contributing to the management of experimental animal genetic resources.

Complete Mitochondrial Genomes of Nedyopus patrioticus: New Insights into the Color Polymorphism of Millipedes.

There has been debate about whether individuals with different color phenotypes should have different taxonomic status. In order to determine whether the different color phenotypes of Nedyopus patrioticus require separate taxonomic status or are simply synonyms, here, the complete mitochondrial genomes (mitogenomes) of two different colored N. patrioticus, i.e., red N. patrioticus and white N. patrioticus, are presented. The two mitogenomes were 15,781 bp and 15,798 bp in length, respectively. Each mitogenome contained 13 PCGs, 19 tRNAs, 2 rRNAs, and 1 CR, with a lack of trnI, trnL2, and trnV compared to other Polydesmida species. All genes were located on a single strand in two mitogenomes. Mitochondrial DNA analyses revealed that red N. patrioticus and white N. patrioticus did not show clear evolutionary differences. Furthermore, no significant divergence was discovered by means of base composition analysis. As a result, we suggest that white N. patrioticus might be regarded as a synonym for red N. patrioticus. The current findings confirmed the existence of color polymorphism in N. patrioticus, which provides exciting possibilities for future research. It is necessary to apply a combination of molecular and morphological methods in the taxonomy of millipedes.

High-Entropy Fluorite Oxide-Modified CaO-Based Sorbent Pellets for Enhanced High-Temperature CO2 Capture.

The calcium looping technology employing CaO-based sorbents is pivotal for capturing CO2 from flue gas. However, the intrinsic low thermodynamic stability of CaO-based sorbents and the requisite molding step induce severe sintering issues, diminishing their cyclic stability. Herein, a high-entropy fluorite oxide (HEFO) inert stabilizer premised on entropy stabilization and synergistic effect strategies is introduced. HEFO-modified, CaO-based sorbent pellets are synthesized via a rapid cigarette butt-assisted combustion process (15 min) combined with the graphite molding method. Post-multiple cycles, their CO2 capture capacity reaches 0.373 g g-1, which is 2.6-fold superior to that of pure CaO, demonstrating markedly enhanced anti-sintering properties. First, the subtle morphological and crystallographic modifications suggest that the inherent entropy stability of HEFO imparts robust thermal resistance. Concurrently, the disordered structure of single-phase HEFO exhibits a high affinity for CaO, resulting in an interface binding energy of -1.83 eV, in sharp contrast to the -0.112 eV of pure CaO, thereby restricting CaO migration. Additionally, the multi-element synergistic effect of HEFO reduces the energy barrier by 0.15 eV, leading to a 40% and 140% increase in carbonation and calcination rates, respectively. This work presents highly efficient and rapidly synthesized CaO-based sorbent pellets, showcasing promising potential for industrial application.

Comprehensive Multiomics Analyses Establish the Optimal Prognostic Model for Resectable Gastric Cancer : Prognosis Prediction for Resectable GC.

BACKGROUND: Prognostic models based on multiomics data may provide better predictive capability than those established at the single-omics level. Here we aimed to establish a prognostic model for resectable gastric cancer (GC) with multiomics information involving mutational, copy number, transcriptional, methylation, and clinicopathological alterations. PATIENTS AND METHODS: The mutational, copy number, transcriptional, methylation data of 268, 265, 226, and 252 patients with stages I-III GC were downloaded from the TCGA database, respectively. Alterations from all omics were characterized, and prognostic models were established at the individual omics level and optimized at the multiomics level. All models were validated with a cohort of 99 patients with stages I-III GC. RESULTS: TTN, TP53, and MUC16 were among the genes with the highest mutational frequency, while UBR5, ZFHX4, PREX2, and ARID1A exhibited the most prominent copy number variations (CNVs). Upregulated COL10A1, CST1, and HOXC10 and downregulated GAST represented the biggest transcriptional alterations. Aberrant methylation of some well-known genes was revealed, including CLDN18, NDRG4, and SDC2. Many alterations were found to predict the patient prognosis by univariate analysis, while four mutant genes, two CNVs, five transcriptionally altered genes, and seven aberrantly methylated genes were identified as independent risk factors in multivariate analysis. Prognostic models at the single-omics level were established with these alterations, and optimized combination of selected alterations with clinicopathological factors was used to establish a final multiomics model. All single-omics models and the final multiomics model were validated by an independent cohort. The optimal area under the curve (AUC) was 0.73, 0.71, 0.71, and 0.85 for mutational, CNV, transcriptional, and methylation models, respectively. The final multiomics model significantly increased the AUC to 0.92 (P < 0.05). CONCLUSIONS: Multiomics model exhibited significantly better capability in predicting the prognosis of resectable GC than single-omics models.

An Imine-Functionalized Silicone-Based Epoxy Coating with Stable Adhesion and Controllable Degradation for Enhanced Marine Antifouling and Anticorrosion Properties.

Biofouling and corrosion of submerged equipment caused by marine organisms severely restrict the rapid development of the marine industry. Traditional antifouling or anticorrosion coatings typically serve a sole purpose and exhibit limited degradability upon failure, rendering them inadequate for current demands. Herein, a novel imine-functionalized command-degradable bio-based epoxy coating (SAHPEP-DDM) with enhanced integrated antifouling and anticorrosion performances was synthesized utilizing 1,3-bis (3-aminopropyl)-1,1,3,3-tetramethyldisiloxane and syringaldehyde. Compared with commercial epoxy resins (E51-DDM) and polydimethylsiloxanes (PDMS), the SAHPEP-DDM coating exhibits superior antifouling and anticorrosion properties due to the existence of -C=N- and Si-O-Si chain segments in the cross-linking network. The coating achieves resistance rates of 99.59 % and 99.20 % against E. coli and S. aureus, respectively, and shows promising resistance against algae and proteins, as well as excellent corrosion resistance in artificial seawater (with |Z|0.01 Hz and arc radius of about 1011â€…Ω and exceeding 1010â€…Ω respectively). The coating also exhibits excellent chemical resistance in organic solvents as well as neutral and alkaline environments. Moreover, its controlled degradation after coating failure can be achieved in acid aqueous solutions through temperature and acidity adjustments, facilitated by the presence of -C=N-. This work presents a novel degradable coating successfully coupled the dual functions of antifouling and anticorrosion coatings, avoiding the employment of intermediate coat, indicating vast potential for application in various marine engineering fields.

Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/P53 signaling pathway.

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Reinvestigation of Classic T Cell Subsets and Identification of Novel Cell Subpopulations by Single-Cell RNA Sequencing.

Classic T cell subsets are defined by a small set of cell surface markers, while single-cell RNA sequencing (scRNA-seq) clusters cells using genome-wide gene expression profiles. The relationship between scRNA-seq clustered populations (scCPops) and cell surface marker-defined classic T cell subsets remains unclear. In this article, we integrated six bead-enriched T cell subsets with 62,235 single-cell transcriptomes from human PBMCs and clustered them into nine scCPops. Bead-enriched CD4+/CD45RA+/CD25- naive T and CD8+/CD45RA+ naive T cells were mainly clustered into their scCPop counterparts, while cells from the other T cell subsets were assigned to multiple scCPops, including mucosal-associated invariant T cells and NKT cells. The multiple T cell subsets forming one scCPop exhibit similar expression patterns, but not vice versa, indicating scCPop is a more homogeneous cell population with similar cell states. Interestingly, we discovered and named IFN signaling-associated gene (ISAG) high T (ISAGhi T) cells, a T cell subpopulation that highly expressed ISAGs. We further enriched ISAGhi T cells from human PBMCs by FACS of BST2 for scRNA-seq analyses. The ISAGhi T cell cluster disappeared on t-distributed stochastic neighbor embedding plot after removing ISAGs, whereas the ISAGhi T cell cluster showed up by analysis of ISAGs alone, indicating ISAGs are the major contributor of the ISAGhi T cell cluster. BST2+ and BST2- T cells showing different efficiencies of T cell activation indicate that a high level of ISAGs may contribute to quick immune responses.

Dental pulp mesenchymal stem cell-derived exosomes inhibit neuroinflammation and microglial pyroptosis in subarachnoid hemorrhage via the miRNA-197-3p/FOXO3 axis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS: The expressions of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.

The aneurysm occlusion and recurrence of posterior communicating artery aneurysms following the treatment with the pipeline embolization device.

Despite advancements in treatment modalities such as flow diverters, the optimal management of posterior communicating artery (PComA) aneurysms remains uncertain. While PComA aneurysms treated with the Pipeline Embolization Device (PED) has been reported, the characteristics and progression of incomplete occluded aneurysms remain unclear. Therefore, our study aims to investigate the occlusion status and recurrence rates of PComA aneurysms treated with PED. A retrospective review of consecutive PComA aneurysm patients treated with PED was conducted between January 2015 and December 2020. Only patients with radiological follow-up were included. PComA aneurysms were categorized into incomplete occlusion and complete occlusion group. The primary outcomes included the characteristics of incomplete occlusion at the follow-up angiography. Among 121 PComA aneurysms treated with PED at our institution, 80 aneurysms were eligible in our study. During the follow-up period, 19 (23.8%) aneurysms demonstrated incomplete occlusion. Notably, there were no instances of recurrence among the 80 followed-up cases. Baseline characteristics of patients and aneurysms were comparable between the groups with complete and incomplete occlusion. However, the incomplete occlusion group showed a lower rate of assisted coils embolization (21.2% vs. 55.7%, P = 0.017) and shorter median operative time (91.0 vs. 145.5 min, P = 0.039). Differences in functional outcomes, complications, and PComA occlusion status between the groups were not significant. Multivariate analysis revealed the use of coils was associated with lower odds of incomplete PComA aneurysm occlusion (OR 0.01, 95% CI 0.001-0.12; P = 0.001), while aneurysm size was associated with higher odds of incomplete occlusion (OR 1.25, 95% CI 1.10-1.46; P = 0.002). The treatment of PED for PComA aneurysm demonstrated favorable outcomes, with an acceptable rate of incomplete occlusion and no instances of recurrence observed. However, further research is needed to explore the optimal procedural strategy for large-sized PComA aneurysms.

Macroevolution of avian T cell receptor C segments using genomic data.

All jawed vertebrates have four T cell receptor (TCR) chains expressed by thymus-derived lymphocytes that play a significant role in animal immune defense. However, avian TCR studies have been limited to a few species, although their co-functional major histocompatibility complexes (MHCs) have been studied for decades, showing various copy numbers and polymorphisms. Here, using public genome data, we characterized the copy numbers, the phylogenic relationship and selection of T cell receptor complex (TCR-C) segments, and the genomic organization of TCR loci across birds. Various numbers of C segments were found in the TCRα/TCRδ, TCRß, and TCRγ loci, and phylogenetic analysis reflected both ancient gene duplication events (two Cß segments and Cδ segments divergent into CδI and CδII) and contemporary evolution (lineage-specific and species-specific characteristics). Most passerines lack CδII segments and a second TRD locus, except Meliphagidae and Maluridae. A relatively stable structure was verified in four TCR loci of birds, except for the arrangement of V segment groups. In this study, we explored the phylogenetic relationships of TCR-C segments across avians for the first time. We inferred gene duplication and loss events during the evolution process. The finding of diverse TCR germline repertoires provides a better understanding of the immune systems of birds.

Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet ß cells in mice.

BACKGROUND: Albumin is the most abundant protein in serum and serves as a transporter of free fatty acids (FFA) in blood vessels. In type 2 diabetes mellitus (T2DM) patients, the reduced serum albumin level is a risk factor for T2DM development and progression, although this conclusion is controversial. Moreover, there is no study on the effects and mechanisms of albumin administration to relieve T2DM. We examined whether the administration of young and undamaged recombinant albumin can alleviate T2DM in mice. METHODS: The serum albumin levels and metabolic phenotypes including fasting blood glucose, glucose tolerance tests, and glucose-stimulated insulin secretion were studied in db/db mice or diet-induced obesity mice treated with saline or young, undamaged, and ultrapure rMSA. Apoptosis assays were performed at tissue and cell levels to determine the function of rMSA on islet ß cell protection. Metabolic flux and glucose uptake assays were employed to investigate metabolic changes in saline-treated or rMSA-treated mouse hepatocytes and compared their sensitivity to insulin treatments. RESULTS: In this study, treatment of T2DM mice with young, undamaged, and ultrapure recombinant mouse serum albumin (rMSA) increased their serum albumin levels, which resulted in a reversal of the disease including reduced fasting blood glucose levels, improved glucose tolerance, increased glucose-stimulated insulin secretion, and alleviated islet atrophy. At the cellular level, rMSA improved glucose uptake and glycolysis in hepatocytes. Mechanistically, rMSA reduced the binding between CAV1 and EGFR to increase EGFR activation leading to PI3K-AKT activation. Furthermore, rMSA extracellularly reduced the rate of fatty acid uptake by islet ß-cells, which relieved the accumulation of intracellular ceramide, endoplasmic reticulum stress, and apoptosis. This study provided the first clear demonstration that injections of rMSA can alleviate T2DM in mice. CONCLUSION: Our study demonstrates that increasing serum albumin levels can promote glucose homeostasis and protect islet ß cells, which alleviates T2DM.

Molecular Hinges by Fusion of Pyrrole and Dithiin: Synthesis, Structure, Redox Chemistry and Host-Guest Complexation of Dipyrrolo-1,4-dithiins.

A series of novel hinge-like molecules, namely dipyrrolo-1,4-dithiins (PDs), were prepared and fully characterized by NMR, UV/vis, cyclic voltammogram, ESR, and single crystal X-ray diffraction (SCXRD) analysis. The lateral fusion of pyrroles with 1,4-dithiins has led to not only retained key features of a dithiin, but also enhanced redox-activity with increased susceptibility to radical cations via redox or chemical oxidation. Stabilization of their radicals are observed for the N,N-tert-butyl or N,N-triphenylmethyl PD as evidenced by ESR measurements. DFT calculations and SCXRD analysis revealed PDs are extremely flexible with adaptive molecular geometries that can be mechanically regulated via crystal packing or host-guest complexation. The excellent donor nature of PDs renders inclusion complexes with the cyclophane bluebox (cyclobis(paraquat-p-phenylene)), featuring association constants up to 104  M-1 . Additionally, a planarized transition intermediate associated with inversion dynamics of a PD has been preserved in the pseudorotaxane structure with assistances of π⋅⋅⋅π and S⋅⋅⋅π interactions. The hinged structure, excellent redox-activity, and adaptive nature of PDs could further enable accesses to exotic redox switchable host-guest chemistry and functional materials.

Aspartoacylase promotes the process of tumour development and is associated with immune infiltrates in gastric cancer.

BACKGROUND: Aspartoacylase (ASPA) is a gene that plays an important role in the metabolic reprogramming of cancer. However, the clinical relevance of ASPA in gastric cancer (GC) has not been demonstrated. METHODS: The link between ASPA and the clinical features of GC was determined using two public genomic databases. The multivariate Cox proportional hazard model and generalised linear regression model were applied to examine whether the ASPA level is associated with the prognosis and other pathological factors. In addition, the role of specific genes in the infiltration of immune cells in the setting of GC was investigated using a further immunological database. The expression level of various proteins was detected using a western blotting assay. Transwell and methyl thiazolyl tetrazolium tests were applied for the detection of cellular invasion and proliferation, with small hairpin ribonucleic acid used to knockdown ASPA. RESULTS: According to the multivariate Cox regression results, the down-regulated ASPA expression is a distinct prognostic factor. Furthermore, ASPA has significant positive correlations with the infiltration of immune cells in GC lesions. Compared to the non-cancer tissues, the GC tissues had a significantly lower level of ASPA expression (p < 0.05). Using knockdown and overexpression techniques, it was demonstrated that ASPA affects the capacity of cell lines for GC to both proliferate and invade. CONCLUSION: Overall, ASPA could promote the occurrence and development of GC and presents a promising predictive biomarker for the disease since it is favourably connected with immune infiltrates and negatively correlated with prognosis.

Radiogenomics to characterize the immune-related prognostic signature associated with biological functions in glioblastoma.

OBJECTIVES: The tumor microenvironment and immune cell infiltration (ICI) associated with glioblastoma (GBM) play a vital role in cancer development, progression, and prognosis. This study aimed to establish an ICI-related prognostic biomarker and explore the associations between ICI signatures and radiomic features in patients with GBM. METHODS: The gene expression and survival data of patients with GBM were obtained from three databases. Based on the ICI pattern, an individualized ICI score for each GBM patient was developed in the discovery set (n = 400) and independently verified in the validation set (n = 374). A total of 5915 radiomic features were extracted from the intratumoral and peritumoral regions. Recursive feature elimination and support vector machine methods were performed to select the key features and generate a model predictive of low- or high- ICI scores. The prognostic value of the identified radio genomic model was examined in an independent dataset (n = 149) using imaging and survival data. RESULTS: We found that higher ICI scores often indicated worse patient prognosis (multivariable hazard ratio: 0.48 and 0.63 in discovery and validation set, respectively) and higher expression levels of immune checkpoint-related genes. A model that combined 11 radiomic features could well distinguish tumors with different ICI scores (AUC = 0.96, accuracy = 94%). This model was proven to be helpful for noninvasive prognostic stratification in an independent validation cohort. CONCLUSIONS: ICI scores may serve as an effective prognostic biomarker to characterize potential biological processes in patients with GBM. This ICI signature can be evaluated noninvasively through radiogenomic analysis. KEY POINTS: • Immune cell infiltration (ICI) scores can serve as an effective prognostic biomarker in patients with glioblastoma. • The ICI signature can be evaluated noninvasively through radiomic features derived from the intratumoral and peritumoral regions. • The prognostic value of the radiogenomic model can be verified by independent survival and MRI data.

Structural plasticity of the contralesional hippocampus and its subfields in patients with glioma.

OBJECTIVES: To characterize the structural plasticity of the contralesional hippocampus and its subfields in patients with unilateral glioma. METHODS: 3D T1-weighted MRI images were collected from 55 patients with tumors infiltrating the left (HipL, n = 27) or right (HipR, n = 28) hippocampus, along with 30 age- and sex-matched healthy controls (HC). Gray matter volume differences of the contralesional hippocampal regions and three control regions (superior frontal gyrus, caudate nucleus, and superior occipital gyrus) were evaluated using voxel-based morphometry (VBM) analyses. Volumetric differences in the hippocampus and its subregional volume were measured using the FreeSurfer software. RESULTS: Compared with HC, patients with unilateral hippocampal glioma exhibited significantly larger gray matter volume in the contralesional hippocampus and parahippocampal regions (cluster = 571 voxels for HipL; cluster 1 = 538 voxels and cluster 2 = 88 voxels for HipR; family-wise error corrected p < 0.05). No significant alterations were found in control regions. Volumetric analyses showed the same trend in the contralesional hippocampal subregions for both patient groups, including the CA1 head, CA3 head, hippocampus amygdala transition area (HATA), fimbria, and the granule cell molecular layer of the dentate gyrus head (GC-ML-DG head). Notably, the differences of the contralesional HATA (HipL: η2 = 0.418, corrected p = 0.002; HipR: η2 = 0.313, corrected p = 0.052) and fimbria (HipL: η2 = 0.450, corrected p < 0.001; HipR: η2 = 0.358, corrected p = 0.012) still held after the Bonferroni correction. CONCLUSIONS: Our findings provide evidence for macrostructural plasticity of the contralateral hippocampus in patients with unilateral hippocampal glioma. Specifically, HATA and fimbria exhibit great potential in this process. KEY POINTS: • Glioma infiltration of the hippocampal regions induces a significant increase in gray matter volume on the contralateral side. • Specifically, the HATA and fimbria regions exhibit favorable plastic potential in the process of lesion-induced structural remolding.

Fused expression of Sm1-Chit42 proteins for synergistic mycoparasitic response of Trichoderma afroharzianum on Botrytis cinerea.

Sm1 and Chit42 of Trichoderma have been universally confirmed as crucial biocontrol factors against pathogen infection through induced resistance and mycoparasitism, respectively. However, not enough work has been conducted to understand the novel function of fused expression of these two proteins in Trichoderma. The results of this study demonstrated that Sm1-Chit42 protein (SCf) engineered T. afroharzianum strain OE:SCf exerted synergistic inhibition to Botrytis cinerea growth at multiple stages of mycoparasitic interaction of T. afroharzianum and B. cinerea including chemotropism sensing, hyphal coiling, hydrophobicity modulation, cell wall adhesion, virulence reduction and pathogen killing by ROS. These results highlight a novel mycoparasitic system in Trichoderma strains engineered with Sm1-Chit42 chimeric protein to combat B. cinerea growth and reproduction, which would lay a strong foundation for exploring a new engineered Trichoderma biofungicide created with chimeric proteins in the future.

Efficient Exploration of Chemical Compound Space Using Active Learning for Prediction of Thermodynamic Properties of Alkane Molecules.

We introduce an exploratory active learning (AL) algorithm using Gaussian process regression and marginalized graph kernel (GPR-MGK) to sample chemical compound space (CCS) at minimal cost. Targeting 251,728 enumerated alkane molecules with 4-19 carbon atoms, we applied the AL algorithm to select a diverse and representative set of molecules and then conducted high-throughput molecular simulations on these selected molecules. To demonstrate the power of the AL algorithm, we built directed message-passing neural networks (D-MPNN) using simulation data as the training set to predict liquid densities, heat capacities, and vaporization enthalpies of the CCS. Validations show that D-MPNN models built on the smallest training set considered in this work, which consists of 313 molecules or 0.124% of the original CCS, predict the properties with R2 > 0.99 against the computational data and R2 > 0.94 against the experimental data. The advantage of the presented AL algorithm is that the predicted uncertainty of GPR depends on only the molecular structures, which renders it compatible with high-throughput data generation.

Neurovascular coupling changes in patients with magnetic resonance imaging negative focal epilepsy.

Brain neuron activity is closely related to cerebral blood flow (CBF) changes. Alterations in the regional homogeneity (ReHo) and CBF occur in patients with magnetic resonance imaging negative focal epilepsy (FEP-MRI-). However, the coupling alterations of ReHo and CBF in FEP-MRI- remain unclear. The study aims to explore neurovascular coupling alterations and their clinical implication in FEP-MRI-. We collected resting-state magnetic resonance imaging (MRI) data from 31 healthy controls (HCs) and 48 patients with FEP-MRI-,including three-dimensional (3D) T1-weighted imaging, 3D arterial spin labeling (ASL) imaging,and resting-state functional MRI (rs-fMRI). The CBF and ReHo values were calculated from the ASL and rs-fMRI data, respectively. The CBF/ReHo ratio per voxel and whole-brain CBF-ReHo coupling were compared between the two groups. Correlation analysis involved the CBF/ReHo ratio and clinical indicators in FEP-MRI-. Patients with FEP-MRI- showed significantly increased cross-subject CBF-ReHo and global cross-voxel CBF-ReHo coupling. The CBF/ReHo ratio was higher in the bilateral orbitofrontal gyrus, right parietal lobe, and right middle frontal gyrus of patients with FEP-MRI-. Nevertheless, this ratio was lower in the bilateral supplementary motor areas, the left middle and posterior cingulate gyrus, and the right central sulcus cover. The CBF/ReHo ratio was markedly correlated with cognitive function, memory, intelligence, and epilepsy duration in the above abnormal brain regions. CBF/ReHo ratio may be useful as an indicator of neuropathological mechanisms. These results support the hypothesis that CBF/ReHo ratio relates to the neuropathological mechanisms of FEP-MRI-. Furthermore, it offers new perspectives for studying the mechanisms of MRI-negative epilepsy.