Integration of protein sequence and protein-protein interaction data by hypergraph learning to identify novel protein complexes.

Protein-protein interactions (PPIs) are the basis of many important biological processes, with protein complexes being the key forms implementing these interactions. Understanding protein complexes and their functions is critical for elucidating mechanisms of life processes, disease diagnosis and treatment and drug development. However, experimental methods for identifying protein complexes have many limitations. Therefore, it is necessary to use computational methods to predict protein complexes. Protein sequences can indicate the structure and biological functions of proteins, while also determining their binding abilities with other proteins, influencing the formation of protein complexes. Integrating these characteristics to predict protein complexes is very promising, but currently there is no effective framework that can utilize both protein sequence and PPI network topology for complex prediction. To address this challenge, we have developed HyperGraphComplex, a method based on hypergraph variational autoencoder that can capture expressive features from protein sequences without feature engineering, while also considering topological properties in PPI networks, to predict protein complexes. Experiment results demonstrated that HyperGraphComplex achieves satisfactory predictive performance when compared with state-of-art methods. Further bioinformatics analysis shows that the predicted protein complexes have similar attributes to known ones. Moreover, case studies corroborated the remarkable predictive capability of our model in identifying protein complexes, including 3 that were not only experimentally validated by recent studies but also exhibited high-confidence structural predictions from AlphaFold-Multimer. We believe that the HyperGraphComplex algorithm and our provided proteome-wide high-confidence protein complex prediction dataset will help elucidate how proteins regulate cellular processes in the form of complexes, and facilitate disease diagnosis and treatment and drug development. Source codes are available at https://github.com/LiDlab/HyperGraphComplex.

Mediation of White Matter Alterations in the Association Between Ventricular Dilation and Cognitive Decline in Hydrocephalus Patients: An MRI Study.

BACKGROUND: Cognitive impairment is commonly observed in hydrocephalus patients. Ventricular enlargement compresses brain parenchyma, especially the white matter (WM). PURPOSE: To investigate whether the relationship between ventricular dilation and cognitive decline in hydrocephalus patients is mediated by WM alterations. STUDY TYPE: Retrospective. POPULATION: 51 communicating hydrocephalus patients (median age, 54 years), 50 obstructive hydrocephalus patients (median age, 49 years), and 53 control subjects (median age, 50 years). FIELD STRENGTH/SEQUENCE: Diffusion tensors imaging, 3D T1 BRAVO, 3D FIESTA, CUBE T2, and FLAIR sequences at 3T. ASSESSMENT: DTI parameters (skeletonized fractional anisotropy (FA), skeletonized mean diffusivity (MD), and peak width of skeletonized mean diffusivity p(PSMD)) were extracted using FSL software. Global, periventricular, and deep white matter hyperintensity (WMH) volumes, degree of ventricular enlargement (Evans index), and other conventional imaging markers (number of lacunes and perivascular spaces, intracranial and brain volume) were extracted using united imaging intelligence. Cognitive tests included Montreal cognitive assessment (MoCA), clock drawing test (CDT), and vocabulary fluency test (VFT). STATISTICAL TESTS: Multivariable linear regression analysis, mediation analyses, and dominance analysis. P-value <0.05 was considered significant. RESULTS: The degree of ventricular dilation, DTI parameters, and cognitive function scores were interrelated. The skeletonized FA values (ß = -0.0917, 95% confidence interval (CI): -0.205, -0.024) and normalized global WMH volume (ß = -0.0635, 95% CI: -0.13, -0.0005) together mediated 37.2% of the association between Evans index and MoCA. A comparable causal pathway was found for periventricular WMHs but not for deep WMHs. Dominance analysis indicated skeletonized FA values had a greater impact on cognition than WMH volume. The skeletonized FA values also mediated the association between Evans index and CDT (ß = -0.0897, 95% CI: -0.165, -0.026) and VFT (ß = -0.1589, 95% CI: -0.27, -0.083). CONCLUSION: WM alterations were causal mediators between ventricular dilation and cognitive decline in hydrocephalus patients. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Primitive new termites (Blattodea, Termitoidae) in Cretaceous amber from Myanmar.

Mastotermitidae, the first-diverging extant family of termites, has only one relic extant species; however, this family had greater richness during the Mesozoic and Cenozoic eras. Fossil termites from the Cretaceous provide information on the early evolution of termites and the transition between extinct families. Herein, two new Mastotermitidae species found in upper Cretaceous (Cenomanian) Kachin amber are reported. One is a female imago described as Angustitermesreflexusgen. et sp. nov. and assigned to the subfamily Mastotermitinae. The other is Mastotermesreticulatussp. nov., which is described from an isolated forewing. With the comparison especially of the antenna and venation, these new mastotermitids further increase our knowledge of the diversity and morphology of Mastotermitidae during the Mesozoic.

Dyadic coping, resilience, and quality of life in young and middle-aged couples after gynecologic cancer: An actor-partner interdependence mediation model.

PURPOSE: To examine the effects of dyadic coping on quality of life (QoL) and the mediating role of resilience in these effects among young and middle-aged couples after gynecologic cancer (GC). METHODS: A cross-sectional study was conducted between July 2022 and June 2023 from one tertiary hospital in Wuhan, China. 240 pairs of young and middle-aged GC couples were recruited. The demographic and clinical characteristics questionnaire, the Dyadic Coping Inventory, the 10-item Connor-Davidson Resilience Scale, and the 12-item Short-Form Health Survey were used to collect data. The process of dyadic analysis was based on the actor-partner interdependence mediation model. RESULTS: GC patients' dyadic coping had an actor effect on both their own physical and mental QoL, while spouses' dyadic coping only exerted an actor effect on their own mental QoL. The mediating effects of resilience on the relationship between dyadic coping and QoL were identified in dyads. Moreover, spouses' dyadic coping could indirectly influence patients' QoL through their own and patients' resilience. CONCLUSION: The findings confirm the dyadic relationships between dyadic coping, resilience, and QoL among young and middle-aged couples facing GC. These results suggest that it is necessary to develop couple-based interventions to improve dyadic coping and resilience, thus enhancing the QoL of both members.

Three-dimensional pseudocontinuous arterial spin labeling with dual postlabeling delay for reflecting cerebral blood flow regulation in patients with hydrocephalus: a retrospective cross-sectional study.

Background: Three-dimensional pseudo-continuous arterial spin-labeling (3D pCASL) with dual postlabeling delay (PLD) captures both early and delayed cerebral blood flow (CBF), yet its potential in reflecting blood flow regulation in hydrocephalus patients remains uncertain. This study investigated the hemodynamic characteristics in patients with hydrocephalus and whether the difference in cerebral blood flow using short and long PLDs (ΔCBF = CBFPLD =2.5 s - CBFPLD =1.5 s) could reflect cerebral regulation and further aimed to demonstrate the associations between regional ΔCBF and the degree of ventricular dilatation. Methods: This retrospective study included consecutive patients with hydrocephalus and control participants attending The Second Affiliated Hospital of Nanchang University from December 2017 to December 2022. The CBF in 18 brain regions was manually delineated by two radiologists. Regional CBF and ΔCBF were compared via covariance analyses. The associations between ΔCBF and the degree of ventricular dilatation were investigated using linear regression analyses and interaction analysis. Results: In total, 58 patients with communicating hydrocephalus, 57 patients with obstructive hydrocephalus, and 52 controls were analyzed. CBF of the hydrocephalus groups was lower than that of the control group at the shorter PLD. CBF was higher at a longer PLD, with no difference between the hydrocephalus groups and the control group in some regions. The hydrocephalus groups showed a higher ΔCBF compared to the control group. Furthermore, in the left medial watershed (10.6±5.66 vs. 7.01±5.88 mL/100 g/min; P=0.038), communicating hydrocephalus exhibited greater ΔCBF than did obstructive hydrocephalus. ΔCBF of the right posterior external watershed [adjusted ß: 0.276; 95% confidence interval (CI): 0.047-0.505; P=0.019] and right parietal cortex (adjusted ß: 0.277; 95% CI: 0.056-0.498; P=0.015) in the obstructive hydrocephalus group and ΔCBF of the left internal watershed (adjusted ß: 0.274; 95% CI: 0.013-0.536; P=0.040) in the communicating hydrocephalus group were associated with the degree of ventricular dilatation, respectively. Conclusions: Patients with hydrocephalus showed cerebral regulation in maintaining adequate CBF, resulting in longer arterial transit times. The ability to regulate CBF in brain regions represented by the watershed was associated with the degree of ventricular dilation.

Alteration in gut microbiota is associated with immune imbalance in Graves' disease.

Background: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. Objective: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. Methods: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. Results: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. Conclusion: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.