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Introduction: Medullary thyroid carcinoma (MTC) is aggressive and difficult to distinguish from papillary thyroid carcinoma (PTC) using traditional ultrasound. Objective to establish a standard-based ultrasound imaging model for preoperative differentiation of MTC from PTC. Methods: A retrospective study was conducted on the case data of 213 thyroid cancer patients (82 MTC, 90 lesions; 131 PTC, 135 lesions) from the Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital. We constructed clinical model, radiomics model and comprehensive model by executing machine learning algorithms based on baseline clinical, pathological characteristics and ultrasound image data, respectively. Results: The study showed that the comprehensive model observed the highest diagnostic efficacy in differentiating MTC from PTC with AUC, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 0.93, 0.88, 0.82, 0.77, 0.91, 85.8%. Delong test results showed that the comprehensive model was significantly better than the clinical model (Z=-3.791, P<0.001) and the radiomics model (Z=-2.017, P =0.044). Calibration curves indicated the comprehensive model and the radiomics model exhibited better stability than the clinical model. Decision curves analysis (DCA) demonstrated that the comprehensive model had the highest clinical net benefit. Discussions: Radiomics model is effective in identifying MTC and PTC preoperatively, and the comprehensive model is better. This approach can aid in identifying the pathologic types of thyroid nodule before clinical operation, supporting personalized medicine in the decision-making process. [ABSTRACT FROM AUTHOR]

Childhood maltreatment stands out as a pivotal risk factor for depression, with gene-by-environment interaction serving as a crucial mechanism. Here we perform genome-wide interaction analyzes of childhood maltreatment in the UK Biobank, integrating methylation evidence through colocalization analysis and identifying associated brain structure abnormalities from childhood to adulthood. A genome-wide significant genomic region interacting with childhood maltreatment is identified at 8p11.21 (IDO2 rs7846217, P = 2.02e–08), implicating the tryptophan-kynurenine pathway. Colocalization analysis reveals that IDO2 rs11777027, rs2340953 and rs28631334 are associated with depression in individuals exposed to childhood maltreatment and colocalize with methylation signals in both blood and brain for IDO2. These interactions affect cortical thickness of the left supramarginal gyrus in children (P = 9.72e–04) and adults (P = 1.34e–04), as well as cortical volume in the right angular gyrus in children (P = 1.02e–04). Furthermore, the interactions significantly predict new-onset depression at a 2-year follow-up in children. Stunted increase in cortical thickness of the left middle-anterior cingulate gyrus and sulcus significantly mediates the interaction between childhood maltreatment and IDO2 on childhood depression. These interactions also moderate antidepressant treatment efficacy at 4–6 weeks. Childhood maltreatment interacts with genes to increase depression risk. Here, Sun et al. use a genome-wide approach to identify variants of IDO2 associated with depression in individuals who have undergone child maltreatment. [ABSTRACT FROM AUTHOR]

Background and Aims: Cystatin B (CSTB) has been demonstrated to play a significant role in the pathogenesis of a number of diseases, including the evolution and progression of multiple cancers. Nevertheless, the function of CSTB in intrahepatic cholangiocarcinoma (iCCA) is yet to be fully elucidated. Methods: By analyzing transcriptome sequencing data from the FU-iCCA cohort, the iCCA-27 cohort, and three public databases, we identified genes associated with iCCA prognosis and selected CSTB as the subject of our study. The expression of CSTB was examined between tumor tissues and adjacent normal tissues obtained from iCCA patients via Western blot analysis. The clinical significance of CSTB was analyzed through immunohistochemical staining of a tissue microarray. Subsequently, the biological effects of CSTB overexpression or knockdown on iCCA cells were evaluated in vitro and in vivo. Results: CSTB expression was markedly elevated in the CCA pathological tissues in comparison to the corresponding adjacent normal tissues. A correlation was identified between higher CSTB expression and poorer patient prognosis in the analysis of 176 iCCA patients. It is noteworthy that overexpression or knockdown experiments demonstrated that CSTB plays a role in the proliferation, migration, and invasion of cells. In subcutaneous tumor models in nude mice, the knockdown of CSTB resulted in smaller tumors in terms of size and weight, and a slower growth rate. Conclusions: CSTB plays a significant function in the regulation of iCCA progression and may serve as a promising biomarker for iCCA. [ABSTRACT FROM AUTHOR]

Relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are frequently aggressive and associated with unfavorable prognoses. Pan-targeted Chimeric Antigen Receptor (CAR) T-cell therapy have shown promising results in clinical trials. In recent years, CD7 CAR T-cell and CD5 CAR T-cell demonstrate effectiveness in treating r/r T-ALL/LBL patients with bone marrow infiltration. However, nearly half of r/r T-ALL/T-LBL patients are accompanied by extramedullary disease (EMD), where comprehensive data on the efficacy and safety of CAR T-cell therapy remain limited. Additionally, CD7 CAR T-cell and CD5 CAR T-cell therapy can cause severe immunodeficiency and hematologic toxicity, complicating with difficult immune reconstitution. This review provides an in-depth analysis of the safety profile and adverse events associated with CAR T-cell therapy in r/r T-ALL/LBL, with a a particular emphasis on its impact in patients with EMD. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis. [ABSTRACT FROM AUTHOR]

Background: Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear. Aims: To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease. Method: A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes. Results: Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03–2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002–1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74–6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16–3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22–3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01–2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease. Conclusions: This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake. [ABSTRACT FROM AUTHOR]

The active deforming southeastern margin of the Tibetan Plateau has developed series of fault basins filled with fluvial-lacustrine sediment deposited by drainage systems during every stage of its uplifting, the records of Cenozoic sedimentary sequence and detrital provenance in these basins are often obscure, making the interpretation of the drainage reorganization quite difficult. This research discovered the earliest Late Cenozoic fluvial conglomerate in the Yuanmou Basin, one of the fault basins in SE Tibet, and named the conglomerate as 'the Yuanmou Gravel Layer (YMG)'. Clast petrography, morphology and paleocurrent directions of the YMG indicate that the conglomerate is the remain of a large paleo river traversing through the Yuanmou Basin from north to south. Detrital zircon U-Pb ages can imply the YMG has similar provenance areas with Anning, Dadu and Yalong rivers at age peaks of 175–275, 600–1 000, and 2 100–2 700 Ma, but the lack of the age peak of 30–100 Ma from Qiangtang Block implies that the paleo-river was not yet connected with the Jinsha River during the YMG's accumulation. The fluvial-lacustrine strata with gravel beds containing paleosimian fossils comparable to the YMG were deposited ∼7–11 Ma, further suggesting that the pre-formed south-flowing river was active during the Late Miocene. [ABSTRACT FROM AUTHOR]

Background and Aims: The immune microenvironment (IME) plays a crucial role in the progression of hepatocellular carcinoma (HCC). In HCC, the IME is often compromised by hepatitis B virus (HBV) infection, chronic inflammation, and fibrosis. Both antiviral therapy (AVT) and the alleviation of inflammation and fibrosis (AIF) have been shown to improve prognosis. However, the relationship among the IME of HCC, AVT, and AIF remains unclear. Methods: A total of 140 and 110 primary HBV‐related HCC patients were enrolled as training and validation sets, respectively, to establish a HCC‐immune microenvironment score (H‐IME score). Immunohistochemistry was performed to assess the number of granzyme B+ (GrB+) and Foxp3+ cells, as well as the expression of CTLA‐4, PD‐1, LAG3, TIGIT, TIM3, and VISTA. Another cohort consisting of 114 recurrent HBV‐related HCC patients with paired primary and recurrent tissues was used to study the relationship among the IME of HCC, AVT, and AIF. Results: The H‐IME score, including GrB, Foxp3, CTLA‐4, PD‐1, LAG3, and TIGIT, was established to evaluate the IME. A higher H‐IME score indicates stronger immunosuppressive activities. Both AVT and AIF were found to inhibit immunosuppressive activities in the IME. Compared to primary tumors, the H‐IME scores of recurrent tumors in the effective AVT group (e‐AVT, classified by HBV DNA) with AIF decreased, while the scores increased in the non‐AVT group without AIF. Conclusions: The IME of HCC is closely related to AVT and AIF. e‐AVT can enhance anti‐tumor activities in the IME by alleviating inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Enhancing forest ecological functioning by optimizing stand structure is essential in high-quality, sustainable forests. We examined this in 38 plots (20 m × 20 m) of Pinus tabuliformis forests in the mountainous area of Beijing. We investigated and analyzed the spatial structure and functional characteristics of these plots. Structural equation modeling and response surface methodology were used to identify spatial structural stand factors affecting soil nutrient levels and understory biodiversity. We examined the pathways and strengths of the coupling relationships between structure and function and the ranges and thresholds of changes in these structural factors. Mingling degree, openness degree, competition index, and forest layer index substantially affected the understory herbaceous species diversity and soil nutrient levels. Mingling degree significantly impacted understory biodiversity and soil nutrient levels (direct path coefficient (DPC), 0.48 and 0.70, respectively). Openness degree significantly affected understory species diversity (DPC, 0.37). The competition index and forest layer index exerted less significant direct impacts on these functions; competition influenced herbaceous diversity primarily indirectly. The optimal features were as follows: mingling degree, 0.8; openness degree, 1.1; competition index, 0.3; and forest layer index, 0.5. Average understory herbaceous species diversity and soil nutrient levels are projected to increase by ca. 47.74% and 52.29%, respectively, post optimization. These findings provide a reference for precise regulated stand structures and establish multifunction management optimization objectives in Beijing's mountainous Pinus tabuliformis forests. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe psychiatric disorder with high heritability, characterized by positive and negative symptoms as well as cognitive abnormalities. Dysfunction in glutamate synapse is strongly implicated in the pathophysiology of schizophrenia. However, the precise role of the perturbed glutamatergic system in contributing to the cognitive abnormalities of schizophrenia at the synaptic level remains largely unknown. Although our previous work found that Opcml promotes spine maturation and Opcml-deficient mice exhibit schizophrenia-related cognitive impairments, the synaptic mechanism remains unclear. By using whole-cell patch clamp recording, we found that decreased neuronal excitability and alterations in intrinsic membrane properties of CA1 PNs in Opcml-deficient mice. Furthermore, Opcml deficiency leads to impaired glutamatergic transmission in hippocampus, which is closely related to postsynaptic AMPA/NMDA receptors dysfunction, resulting in the disturbances of E/I balance. Additionally, we found that the aripiprazole which we used to ameliorate abnormal cognitive behaviors also rescued the impaired glutamatergic transmission in Opcml-deficient mice. These findings will help to understand the synaptic mechanism in schizophrenia pathogenesis, providing insights into schizophrenia therapeutics with glutamatergic disruption. [ABSTRACT FROM AUTHOR]

In this article, a compact and portable microwave atmospheric pressure plasma jet (MW‐APPJ) generator based on a coaxial transmission line resonator (CTLR) was proposed. Based on the electromagnetic simulations, the jet generator was designed as a tapered inner conductor structure that ensures plasma generation at low power. A self‐igniting argon (Ar) plasma jet of 10 mm length was generated at an input power of ~20 W and maintained at 2 W. Thanks to the high efficiency of the CTLR structure, plasmas of mixed reactive gases were also realized. Intrinsic plasma parameters and active species were determined using optical emission spectroscopy. Furthermore, the MW‐APPJ device was used to modify the polytetrafluoroethylene surface, and improvement of hydrophilicity was achieved without thermal damage. [ABSTRACT FROM AUTHOR]

Background: Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism in hepatocellular carcinoma (HCC), however, remains to be further investigated. Methods: Bioinformatics approaches were harnessed to scrutinize CBX1's expression profile, its association with tumor staging, and its potential impact on patient outcomes across various cancers. Single-cell RNA sequencing data facilitated the investigation of CBX1 expression patterns at the individual cell level. The CBX1 expression levels in HCC and adjacent non-tumor tissues were quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), and Immunohistochemical analyses. A tissue microarray was employed to explore the relationship between CBX1 levels, patient prognosis, and clinicopathological characteristics in HCC. Various in vitro assays—including CCK-8, colony formation, Transwell invasion, and scratch tests—were conducted to assess the proliferative and motility properties of HCC cells upon modulation of CBX1 expression. Moreover, the functional impact of CBX1 on HCC was further discerned through xenograft studies in nude mice. Results: CBX1 was found to be upregulated in most cancer forms, with heightened expression correlating with adverse patient prognoses. Within the context of HCC, elevated levels of CBX1 were consistently indicative of poorer clinical outcomes. Suppression of CBX1 through knockdown methodologies markedly diminished HCC cell proliferation, invasive capabilities, migratory activity, Epithelial−mesenchymal transition (EMT) processes, and resistance to Tyrosine kinase inhibitors (TKIs). Contrastingly, CBX1 augmentation facilitated the opposite effects. Subsequent investigative efforts revealed CBX1 to be a promoter of EMT and a contributor to increased TKI resistance within HCC cells, mediated via the IGF-1R/AKT/SNAIL signaling axis. The oncogenic activities of CBX1 proved to be attenuable either by AKT pathway inhibition or by targeted silencing of IGF-1R. Conclusions: The broad overexpression of CBX1 in pan-cancer and specifically in HCC positions it as a putative oncogenic entity. It is implicated in forwarding HCC progression and exacerbating TKI resistance through its interaction with the IGF-1R/AKT/SNAIL signaling cascade. [ABSTRACT FROM AUTHOR]

Based on the high-quality observation data and the numerical simulation, the evolution characteristics of internal solitary waves (ISWs) and the load on the suspend submerged body are studied on the continental shelf and slope separately. The observed ISWs exhibit the first mode depression ISWs. The amplitudes of ISWs on the shelf and slope areas reach 50 m and 80 m, respectively. The upper layer velocity in the westward direction is about 0.8 m/s on the continental shelf and 0.9 m/s on the continental slope during the passing through of ISWs. The lower layer is dominated by the eastward compensating flow. In the vertical direction, the water in front of the wave flows downward, while the water behind the wave flows upward, and the maximum vertical velocity exceeds 0.2 m/s. Numerical simulation results show that the larger the amplitude of ISWs, the larger the load on the submerged body. The force on the submerged body by ISWs is dominated by the vertical force, and the corresponding maximum vertical forces on the continental shelf and slope are −25 kN and −27 kN. The submerged body is subjected to a large counterclockwise moment and the sudden change of the moment will also cause the submerged body to capsize. This paper not only gives a deeper understanding of the characteristics of ISWs from the deep continental slope to the shallow continental shelf, but also has a certain guiding value for the prediction of ISWs and for marine military activities. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the interaction between the free surface and a semi/shallowly submerged underwater vehicle, especially when the submergence depth h is smaller than 0.75D (D: submarine maximum diameter). In this respect, the straight-ahead simulations of the generic SUBOFF underwater vehicle geometry are conducted with constant forward velocities using the Unsteady Reynolds-Averaged Navier–Stokes (URANS) equations with a Shear-Stress Transport (SST) k−ω turbulence model in commercial code Fluent, at submergence depths and Froude numbers ranging from h = 0 to h = 3.3D and from Fn = 0.205 to Fn = 0.512, respectively. The numerical models are verified against the existing experimental data. The analysis of the obtained results indicates that in the case of the semi and shallowly submerged underwater vehicle (UV), both the submergence depth and forward velocity have a great effect on the behaviors of hydrodynamic forces acting on the UV. The magnitude of maximum total resistance may reach almost five times the value of resistance exerted on the totally submerged hull. Both the forces acting on the UV and the generated waves when the submergence depth h is smaller than 0.75D are significantly different from those whenr h is larger than 0.75D. The conclusions can be used as reference for future research on near free surface motions of underwater vehicles and the design of small water-plane area twin hull. [ABSTRACT FROM AUTHOR]

Arithmetic ability is critical for daily life, academic achievement, career development, and future economic success. Individual differences in arithmetic skills among children and adolescents are related to variations in brain structures. Most existing studies have used hypothesis-driven region of interest analysis. To identify distributed brain regions related to arithmetic ability, we used data-driven cross-validated predictive models to analyze cross-sectional behavioral and structural MRI data in children and adolescents. The gray matter volume (GMV) of widespread brain regions reliably predicted arithmetic abilities measured by the Comprehensive Mathematical Abilities Test. Furthermore, we applied neuroimaging-transcriptome association analysis to explore transcriptional signatures associated with structural patterns of arithmetic ability. Structural patterns of arithmetic ability primarily correlated with transcriptional profiles enriched for genes involved in transmembrane transport and synaptic signaling. Our findings enhance our understanding of the neural and genetic mechanisms underlying children's arithmetic ability and offer a practical predictor for arithmetic skills during development. [ABSTRACT FROM AUTHOR]

Background : Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. Methods: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 μm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. Results: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. Conclusions: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network. [ABSTRACT FROM AUTHOR]

To elucidate the brain‐wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information‐resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time‐series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally‐specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole‐brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean‐field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms. [ABSTRACT FROM AUTHOR]

The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index < 8.62 and hsCRP < 2 mg/L, patients in the group of TyG index ≥ 8.62 and hsCRP ≥ 2 mg/L had a 3.9 times higher hazard ratio for developing MACE. The addition of both TyG index and hsCRP had an incremental effect on the predictive ability of the GRACE risk score-based prognostic model for MACE (C-statistic: increased from 0.631 to 0.661; cNRI: 0.146, P = 0.012; IDI: 0.009, P < 0.001). In conclusion, there was a significant interaction between the TyG index and hsCRP for the risk of MACE, and the TyG index was reliably and independently associated with MACE only when hsCRP levels were less than 2 mg/L. Furthermore, high TyG index and high hsCRP levels synergistically increased the risk of MACE, suggesting that the prognostic value of TyG index combined with hsCRP might be promising in patients with ACS undergoing PCI. [ABSTRACT FROM AUTHOR]

Objectives: Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma. Dual-energy computed tomography (DECT) is a highly sensitive technique that can determine the iodine concentration (IC) in tumour and provide an indirect evaluation of internal microcirculatory perfusion. This study aimed to assess whether the combination of DECT with laboratory data can improve preoperative MVI prediction. Methods: This retrospective study enrolled 119 patients who underwent DECT liver angiography at 2 medical centres preoperatively. To compare DECT parameters and laboratory findings between MVI-negative and MVI-positive groups, Mann-Whitney U test was used. Additionally, principal component analysis (PCA) was conducted to determine fundamental components. Mann-Whitney U test was applied to determine whether the principal component (PC) scores varied across MVI groups. Finally, a general linear classifier was used to assess the classification ability of each PC score. Results: Significant differences were noted (P < .05) in alpha-fetoprotein (AFP) level, normalized arterial phase IC, and normalized portal phase IC between the MVI groups in the primary and validation datasets. The PC1-PC4 accounted for 67.9% of the variance in the primary dataset, with loadings of 24.1%, 16%, 15.4%, and 12.4%, respectively. In both primary and validation datasets, PC3 and PC4 were significantly different across MVI groups, with area under the curve values of 0.8410 and 0.8373, respectively. Conclusions: The recombination of DECT IC and laboratory features based on varying factor loadings can well predict MVI preoperatively. Advances in knowledge: Utilizing PCA, the amalgamation of DECT IC and laboratory features, considering diverse factor loadings, showed substantial promise in accurately classifying MVI. There have been limited endeavours to establish such a combination, offering a novel paradigm for comprehending data in related research endeavours. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the lipemia removal efficiency of highspeed centrifugation, lipid scavengers, and dilution for biochemical analytes. Methods: We collected 30 cases of lipemic plasma in an emergency laboratory and divided them into 4 aliquots. Lipemia was removed by highspeed centrifugation, lipid scavenger, dilution, and ultracentrifugation, then analytes were measured by an AU5800 analyzer. Taking ultracentrifugation as reference, the efficiencies of the other three methods were evaluated based on the deviation. Results: When highspeed centrifugation was used for lipemia removal, DBIL (18.62%), and Magnesium (6.09%) could not satisfy the criterion. When lipid scavengers were applied to remove lipemia, CRP (-86.70%), TP (-8.29%), CKMB (-44.85%), DBIL (37.96%), Glu (4.20%) and phosphate (14.32%) were not suggested as lipid scavengers. For dilution, nearly half of the analytes could satisfy the criterion, including AMY (2.41%), CRP (5.54%), ALT (2.85%), GGTL (-1.73%), ALP (-0.04%), Glu (-0.84%), LDH (0.06%), CK (0.68%), BUN (3.80%), CREA (-1.54%), UA (5.42%), and magnesium (0.43%). Conclusions: Neither of the methods for lipid removal could satisfy all emergency department tests for lipid removal. This finding suggests that removing lipemia in the clinical laboratory should be based on the characteristics and the method of testing. [ABSTRACT FROM AUTHOR]

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Objective: To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. Methods: This retrospective observational cohort study included 196 patients, 75–102‐years‐old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini‐Nutritional Assessment—Short Form (MNA‐SF). Patients with MNA‐SF scores of 0–11 and 12–14 were included in the malnutrition and nonmalnutrition groups, respectively. Results: The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p <.05). The incidence of all‐cause death in the malnutrition group was higher than that in the nonmalnutrition group (p =.007). Kaplan–Meier curve indicated that malnutrition patients have a higher risk of all‐cause death (log‐rank test, p =.001) and major bleeding events (p =.017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all‐cause death (HR = 1.780, 95%CI:1.039–3.050, p =.036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p =.026), and there was no significant difference in the proportion of anticoagulation therapy (p =.082) and the incidence of ischemic stroke/systemic embolism (p =.310) between the two groups. Conclusions: Malnutrition is an independent risk factor of all‐cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious. [ABSTRACT FROM AUTHOR]

Background & aims: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. Methods: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. Results: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3β/β-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. Conclusions: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response. [ABSTRACT FROM AUTHOR]

The etiology and pathophysiology of heart failure are still unknown. Increasing evidence suggests that abnormal microRNAs (miRNAs) and transcription factors (TFs) expression may be associated with the development of heart failure. Therefore, this study aims to explore key miRNAs, TFs, and related genes in heart failure to gain a greater understanding of the pathogenesis of heart failure. To search and download the dataset of mRNA chips related to heart failure from the GEO database (GSE59867, GSE9128, and GSE134766), we analyzed differential genes and screened the common differentially expressed genes on two chips using R language software. The binary interactions and circuits among miRNAs, TFs, and corresponding genes were determined by Pearson correlation coefficient. A regulatory network of miRNAs, TFs, and target genes was constructed based on bioinformatics. By comparing the sequences of patients with and without heart failure, five downregulated genes with hypermethylated mRNA and three upregulated genes with hypomethylated mRNA were identified. The miRNA-TF gene regulatory network consisted of 26 miRNAs, 22 TFs and six genes. GO and KEGG analysis results revealed that BP terms like cellular response to organic substance, cellular response to cytokine stimulus, and KEGG pathways like osteoclast differentiation, MAPK signaling pathway, and legionellosis were enriched of the DEGs. TMEM87A, PPP2R2A, DUSP1, and miR-92a have great potential as biomarkers for heart failure. The integrated analysis of the mRNA expression spectrum and microRNA-transcription factor-gene revealed the regulatory network of heart failure, which may provide clues to its alternative treatment. [ABSTRACT FROM AUTHOR]

Three-dimensional inversion based on source growing uses systematic searches. Compared with the regularization inversion, this method has lower computational requirements and faster processing speed. The criteria determining the source growth is crucial for the quality of the results. This study proposes an inversion based on source growing with full-tensor gravity gradiometry data to improve vertical inversion effectiveness. First, a depth weighting function is introduced for the criteria to optimize the determination of source growing at different depths. Second, the weights of different data are adjusted based on the inversion results of single-component gradient data, and a joint inversion method is established. Finally, matrix compression reduces memory occupation and improves computational efficiency. By the tests of synthetic data and real data from Vinton Dome, it is demonstrated that the proposed method can effectively guide source growing, providing stronger ability for distinguishing deep targets and being suitable for the inversion of complex-shaped targets. Furthermore, the method has high computational efficiency and anti-noise ability. [ABSTRACT FROM AUTHOR]

Ionogels, with wide applications in tissue engineering, soft robotics, and flexible iontronic devices, require tunable optical, mechanical, and electrical properties for advanced functionality applications. Here, a facile strategy is reported to tune a set of properties of ionogels via tuning the redox states of the added polyoxometalate (POM) clusters. Upon external electrical stimuli, the POM clusters in the ionogels can be reversibly tuned from a transparent, oxidized state to a blue, reduced state. The redox states of the POM anions influence the POM-polymer interactions, which promotes the in situ modulation of the ionogel properties reversibly over a large window: optical transparency from 91% to 7%, dissipated energy from 0.9 to 3.1 MJ m-3, elastic modulus from 1.5 to 2 MPa, conductivity from 1.6 x 10-4 to 2.2 x 10-4 S cm[sup -1]. Meanwhile, the sensory properties of the ionogels can be modulated simultaneously. For strain sensing and pressure sensing, the GF can be tuned from 2.3 to 7.2, and the sensitivity can be tuned from 0.8 to 1.2 kPa-1. Such an ionogel with tunable optical, mechanical, and electrical properties may find a variety of applications meeting specific demands. The POM functionalization strategy may also bring new insights into the design of the stimuli-responsive ionogels. [ABSTRACT FROM AUTHOR]

As multivalent ion batteries, aluminum ion batteries (AIBs) have broad application prospects. In addition, with the further development of new electrolytes, deep eutectic electrolytes are expected to become a green, inexpensive, safe, and ideal electrolytic liquid system to replace traditional ionic liquid electrolytic systems commonly used in AIBs. Herein, we prepared an AlCl3–acetamide (AcAm) electrolyte and systematically analyzed its ion transport capacity at different molar ratios of its components. Consequently, a compositional ratio of 1 : 1.4 of AcAm : AlCl3 provided the best ion transport capacity, exhibiting an exceptional electrochemical performance with high reversible capacity, excellent rate performance, and excellent cycling performance. The graphite material in the electrolytic liquid system showed a typical charge storage mechanism dominated by diffusion-controlled processes, indicating that the charge storage behavior of the graphite electrode in this type of electrolyte battery is dependent on ion intercalation. Additionally, the main structure of the graphite material showed little to no change during a long electrochemical test cycle, suggesting its high structural stability. This research shows that the amide electrolyte has great potential for electrochemical application and broad application prospect. [ABSTRACT FROM AUTHOR]

Background: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals' choices of residence but also modulate how the living environment affects responses to episodic memory. Methods: We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments. Results: Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10−6). These findings were confirmed in the replication sample. Conclusions: We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes. [ABSTRACT FROM AUTHOR]

Confocal optical microscopy and tip-enhanced optical microscopy are applied to characterize the defect distributions in chemical vapor deposition-grown WS2 monolayer triangles qualitatively and quantitatively. The presence of defects in individual monolayer WS2 triangles is revealed with diffraction-limited spatial resolution in their photoluminescence (PL) images, from which the inhomogeneous defect density distribution is calculated, showing an inverse relationship to the PL intensity. The defect-related surface-enhanced Raman spectroscopy (SERS) effect is investigated by depositing a thin copper phthalocyanine layer (5 nm) as the probe molecule on the monolayer WS2 triangles surface. Higher SERS enhancement effects are observed at the defect-rich areas. Furthermore, tip-enhanced optical measurements are performed, which can reveal morphologically defected areas invisible in the confocal optical measurements. Furthermore, the area with high defect density appears brighter than the low-defected area in the tip-enhanced optical measurements, which are different from the observation in the confocal optical measurements. The underlying reasons are attributed to the near-field enhancement of the defect exciton emission induced by the optically excited tip and to an improved coupling efficiency between the tip-generated near-field with the altered dipole moment orientation at the local defect. [ABSTRACT FROM AUTHOR]

An analytic model is used to calculate the Raman and fluorescence enhancement of a molecule in between two closely spaced gold nanospheres. Instead of using the conventional approach that only the dipolar plasmonic mode is considered, we calculate the electric field enhancement in the nanometre sized gap, by taking account of the higher order modes in one gold sphere, which couples to the dipolar mode of the other sphere. The experimental confirmation is performed by gap-dependent tip-enhanced Raman spectroscopy (TERS) measurements. The photoluminescence and Raman enhancement are both observed with different growing trends as the gap width decreases. Red-shift of the background spectra is observed and implies the increasing coupling between the nanospheres. This analytic model is shown to be able to interpret the enhancement mechanisms underlying gap-dependent TERS experimental results. [ABSTRACT FROM AUTHOR]

This study explored whether anticoagulation is safe for frail and non-frail elderly patients who have nonvalvular atrial fibrillation (NVAF). Methods: At hospital discharge, the anticoagulant regimen and frailty status were recorded for 361 elderly patients (aged ≥ 75 y) with NVAF. The patients were followed for 12 months. The endpoints included occurrence of thrombosis; bleeding; all-cause death; and cardiovascular events. Results: At hospital discharge, frailty affected 50.42% of the population and the anticoagulation rate was 44.04%. At discharge, age (OR 0.948, P = 0.006), paroxysmal NVAF (OR 0.384, P < 0.001), and bleeding history (OR 0.396, P = 0.001) were associated with a decrease in rate of receiving anticoagulation, while thrombotic events during hospitalization (OR 2.281, P = 0.021) were associated with an increase. Relative to non-frail patients, those with frailty showed a higher rate of ischemic stroke (5.33% cf. 3.01%), bleeding (P = 0.006) events, and all-cause mortality (P = 0.001). Relative to the group without anticoagulation, in those with anticoagulation the rate of thrombotic events was lower (6.99 cf. 10.98%) and bleeding events were higher (20.98 cf. 12.72%), but the risk of major bleeding was comparable. Conclusion: In the elderly patients with NVAF, the decision toward anticoagulation therapy at hospital discharge was influenced by age, bleeding history, paroxysmal atrial fibrillation diagnosis, and absence of thrombosis. Frail patients were at greater risk of bleeding and all-cause mortality. Anticoagulation tended to reduce the risk of thrombotic events. [ABSTRACT FROM AUTHOR]

To realize the low-resistance shape optimization design of amphibious robots, an efficient optimization design framework is proposed to improve the geometric deformation flexibility and optimization efficiency. In the proposed framework, the free-form deformation parametric model of the flat slender body is established and an analytical calculation method for the height constraints is derived. CFD method is introduced to carry out the high-precision resistance calculation and a constrained Kriging-based optimization method is built to improve the optimization efficiency by circularly infilling the new sample points which satisfying the constraints. Finally, the shape of an amphibious robot example is optimized to get the low-resistance shape and the results demonstrate that the presented optimization design framework has the advantages of simplicity, flexibility and high efficiency. [ABSTRACT FROM AUTHOR]

Background: Alterations in surface area (SA) in specific regions of the cortex have been reported in many individuals with autism spectrum disorder (ASD), however, the genetic background between ASD and SA is still unclear. This study estimated the genetic correlation and causal effect of ASD and cortical SA. Methods: Summarized data of genome-wide association studies (GWAS) were separately downloaded from the Psychiatric Genomics Consortium (18,381 cases of ASD, and 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 participants of Europeans). We used Linkage disequilibrium score regression (LDSC) and Heritability Estimation from Summary Statistics (HESS) to calculate the heritability of each trait. As for the genetic correlation between ASD and SA, LDSC was used for global correlation and HESS was used to examine the local genetic covariance further. We used three Mendelian randomization (MR) methods, Inverse-variance weighted, MR-Egger, and weighted median to estimate the causal relationship. Results: LDSC observed a nominal significant genetic correlation (rg = 0.1229, P-value = 0.0346) between ASD and SA of the rostral anterior cingulate gyrus whereas analysis through HESS did not reveal any significant loci having genetic covariance. Based on MR results, statistically meaningful estimations were found in the following areas, postcentral cortex (β (SE) = 21.82 (7.84) mm, 95% CI: 6.46 to 37.19 mm, PIVW = 5.38 × 10− 3, PFDR = 3.09 × 10− 2), posterior cingulate gyrus (β (SE) = 6.23 (2.69) mm, 95% CI: 0.96 to 11.49 mm, PIVW = 2.05 × 10− 2, PFDR = 4.26 × 10− 2), supramarginal gyrus (β (SE) = 19.25 (8.43) mm, 95% CI: 29.29 to 35.77 mm, PIVW = 2.24 × 10− 2, PFDR = 4.31 × 10− 2). Conclusion: Our results provided genetic evidence to support the opinion that individuals with ASD tend to develop differences in cortical SA of special areas. The findings contributed to understanding the genetic relationship between ASD and cortical SA. [ABSTRACT FROM AUTHOR]

2D in‐plane ferroelectric NbOI2 exhibits strong second harmonic generation (SHG) and ultrahigh effective susceptibility. To push forward their applications in nonlinear photonics and optoelectronics, it is highly desirable to understand the emission dipole orientation and tunability of SHG, which is not achieved. Here, by integrating tight focusing from parabolic mirror with back focal plane (BFP) imaging technique, for the first time it is demonstrated that SHG emission of NbOI2 presents purely in‐plane dipole orientation in consistent with numerical simulations, suggesting the in‐plane components of the SHG susceptibility tensor in NbOI2 dominate the emission. Moreover, with the aid of ab‐initio calculations, it is found that the hydrostatic pressure can dramatically change the structure and resultant SHG intensity of NbOI2. Explicitly, SHG intensity endures a slight increase due to the distortion of octahedral at low pressure pressure, and then monotonously decreases due to the improvement of structural symmetry with further increasing pressure, and drastically quenching resulting from the ferroelectric to paraelectric phase transition. This work unambiguously demonstrates the dipole emission behavior of SHG and the relationship between structural evolution and SHG intensity, which provides an avenue for tunable nonlinear optics and optoelectronics. [ABSTRACT FROM AUTHOR]

Avalanche multiphoton photoluminescence (AMPL) is observed from coupled Au–Al nanoantennas under intense laser pumping, which shows more than one order of magnitude emission intensity enhancement and distinct spectral features compared with ordinary metallic photoluminescence. The experiments are conducted by altering the incident laser intensity and polarization using a home-built scanning confocal optical microscope. The results show that AMPL originates from the recombination of avalanche hot carriers that are seeded by multiphoton ionization. Notably, at the excitation stage, multiphoton ionization is shown to be assisted by the local electromagnetic field enhancement produced by coupled plasmonic modes. At the emission step, the giant AMPL intensity can be evaluated as a function of the local field environment and the thermal factor for hot carriers, in accordance with a linear relationship between the power law exponent coefficient and the emitted photon energy. The dramatic change in the spectral profile is explained by spectral linewidth broadening mechanisms. This study offers nanospectroscopic evidence of both the potential optical damages for plasmonic nanostructures and the underlying physical nature of light–matter interactions under a strong laser field; it illustrates the significance of the emerging topics of plasmonic-enhanced spectroscopy and laser-induced breakdown spectroscopy. [ABSTRACT FROM AUTHOR]

In this work, the self-nucleation effect on crystallization was studied for polypropylene with various nucleating agents. The talc was employed to accelerate crystallization of monoclinic α-crystallites, while N, N′-dicyclohexyl-2,6-naphthalenedicarboxamide TMB-5 was used to accelerate the crystallization kinetics and also induce formation of trigonal β-crystallites. To induce self-nucleation effect, the occurrence criterion was assessed by the transition temperatures from various domains and the available temperature width. More importantly, the resulting influences of self-nucleation effect were quantified by the change of crystallization kinetics and the potential polymorphism variation. It was found that the α-nucleating agents of talc broadened the temperature window for inducing Domain II by elevating the transition temperature from Domain I to Domain II. Although β-nucleating agent (β-NA) of N, N′-dicyclohexyl-2,6-naphthalenedicarboxamide TMB-5 elevated cooling crystallization temperature obviously, the temperature window for Domain II was narrowed. It should be emphasized that in presence of β-NA TMB-5, the self-nucleation effect enhances the crystallization of α-crystallite, which show the competition with β-NA TMB-5. At last, the ternary PP/talc/TMB-5 blend was prepared with the same amounts of α-NA talc and β-NA TMB-5 and it exhibits a similar self-nucleation effect of crystallization, indicating the dominant role of β-NA TMB-5. [ABSTRACT FROM AUTHOR]

Background: Brachyura crab is the largest branch of Decapoda crustacean. Phylogenetic relationships within Brachyura remain controversial to be investigated. The mitochondrial genome (mitogenome) is an important molecular marker for studying the phylogenetic relationships of Brachyura. Methods and results: To understand the phylogeny of Brachyura, the three complete mitogenomes from Charybdis annulata, Leptodius exaratus, and Spider crab were sequenced and annotated. Their full length was 15,747, 15,716, and 16,608 bp long, respectively. The first two crabs both contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. However, Spider crab contained 13 PCGs, two rRNA genes, 25 tRNA genes and a control region. The mitogenomes of each of the three crabs exhibited high AT content (67.8%, 69.1%, and 70.8%), with negative AT skews (–0.014, − 0.028, and − 0.017) and GC skews (–0.269, − 0.286, and − 0.341). The gene order of C. annulata was identical to the ancestor of Brachyura. Compared with the ancestor of Brachyura, L. exaratus exhibited the gene rearrangements of Val (V)-rrnS-control region, and Spider crab had the four copies of Lys (K). Phylogenetic analyses indicated that C. annulata belonged to Portunidae family, Portunoidea superfamilies, L. exaratus belonged to Xanthidae family, Xanthoidea superfamilies, and Spider crab belonged to Mithracidae family, Majoidea superfamilies. Phylogenetic analyses showed that the two species (Somanniathelphusa boyangensis and Huananpotamon lichuanense) belonging to the Potamoidea were sister groups to the Thoracotremata, thus supporting the conclusion that Heterotremata is polyphyletic. Conclusion: The results of this study enriched the crab mitogenome database and enabled us to better understand the phylogenetic relationships of Brachyura. [ABSTRACT FROM AUTHOR]

Soil quality is a very important indicator used to assess ecosystem restoration states in terms of vegetation recovery and establishment. Evaluating the soil quality of different vegetation restoration types in mountainous areas of Beijing and identifying their influencing factors would provide a scientific basis and be helpful for vegetation restoration in the future. Six vegetation types (or communities), including Platycladus orientalis (L.) Franco pure forest (POP), Pinus tabulaeformis Carr. pure forest (PTP), Platycladus orientalis–Pinus tabulaeformis mixed forest (PPM), Platycladus orientalis coniferous and broadleaved mixed forest (POCB), Pinus tabulaeformis coniferous and broadleaved mixed forest (PTCB), deciduous broadleaved mixed forest (DBMF), and one area of non-afforested land (NF), with similar stand conditions were selected and fourteen factors of soil physical and chemical characteristics were measured and used to establish a total data set (TDS), while a minimum data set (MDS) was obtained by using the principal component analysis (PCA) and Pearson correlation analysis methods. Two scoring methods, linear (L) and non-linear (NL), were used to calculate the soil quality index (SQI), and the key factors influencing soil quality by vegetation were identified by a general linear model (GLM), PCA, and correlation analysis. The results showed that: (1) The screened MDS indicators which showed good relationships with the SQIs in the study areas were total nitrogen (TN), sand content, total potassium (TK), pH, and available water capacity (AWC). The SQI–NLM method has better applicability. (2) The contribution rates of vegetation to different soil factors accounted for 28.644% (TN), 21.398% (sand content), 24.551% (TK), 16.075% (pH), and 9.332% (AWC). (3) TN showed a positive relationship with all vegetation types; the content of TN in PTCB and DBMF was obviously larger than in the other types in the 0–10 cm layer; PPM, PTCB, and POCB affected the sand content, which showed negative correlativity; and DBMF showed positive correlativity with AWC. The mechanism of how different species affect TN, sand content, and AWC should be focused on and taken into consideration in further studies. [ABSTRACT FROM AUTHOR]

A hallmark of Alzheimer's disease (AD) is the senile plaque, which contains β‐amyloid peptides (Aβ). Ganglioside GM1 is the most common brain ganglioside. However, the mechanism of GM1 in modulating Aβ processing is rarely known. Aβ levels are detected by using Immunohistochemistry (IHC) and enzyme‐linked immune‐sorbent assay (ELISA). Cryo‐electron microscopy (Cryo‐EM) is used to determine the structure of γ‐secretase supplemented with GM1. The levels of the cleavage of amyloid precursor protein (APP)/Cadherin/Notch1 are detected using Western blot analysis. Y maze, object translocation, and Barnes maze are performed to evaluate cognitive functions. GM1 leads to conformational change of γ‐secretase structure and specifically accelerates γ‐secretase cleavage of APP without affecting other substrates including Notch1, potentially through its interaction with the N‐terminal fragment of presenilin 1 (PS1). Reduction of GM1 levels decreases amyloid plaque deposition and improves cognitive dysfunction. This study reveals the mechanism of GM1 in Aβ generation and provides the evidence that decreasing GM1 levels represents a potential strategy in AD treatment. These results provide insights into the detailed mechanism of the effect of GM1 on PS1, representing a step toward the characterization of its novel role in the modulation of γ‐secretase activity and the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Observational studies have investigated the impact of calcium homeostasis on psychiatric disorders; however, the causality of associations is yet to be established. Bidirectional Mendelian randomization (MR) analysis of calcium homeostasis hormones was conducted on nine psychiatric disorders. Calcium, serum 25-hydroxyvitamin D levels (25OHD), parathyroid hormone, and fibroblast growth factor 23 are the major calcium homeostasis hormones. The causality was evaluated by the inverse variance weighted method (IVW) and the MR Steiger test, while Cochran's Q test, the MR-Egger intercept test, funnel plot, and the leave-one-out method were used for sensitivity analyses. Bonferroni correction was used to determine the causative association features (p < 6.94 × 10−4). Schizophrenia (SCZ) was significantly associated with decreased 25OHD concentrations with an estimated effect of −0.0164 (Prandom-effect IVW = 2.39 × 10−7). In the Multivariable MR (MVMR) analysis adjusting for potentially confounding traits including body mass index, obesity, mineral supplements (calcium, fish oil, and vitamin D) and outdoor time (winter and summer), the relationship between SCZ and 25OHD remained. The genetically predicted autism spectrum disorder and bipolar disorder were also nominally associated with decreased 25OHD. This study provided evidence for a causal effect of psychiatric disorders on calcium homeostasis. The clinical monitoring of 25OHD levels in patients with psychiatric disorders is beneficial. [ABSTRACT FROM AUTHOR]

Myelin, a lipid-enriched multi-layer membrane structure, allows for rapid long-distance saltatory conduction of neuronal impulses. Although glycolipids are the predominant types of lipids in the myelin bilayer, the role of glycolipid transfer protein (GLTP), which selectively mediates the transfer of various glycolipids between phospholipid bilayer, in myelin development and maintenance remains unknown at present. In this study, we identified Gltp as the key lipid metabolism gene in myelin-forming oligodendrocytes (OLs) through integrated omics analysis across independent transcriptomic and single-cell sequencing studies. Gene expression analysis revealed that Gltp is selectively expressed in the differentiated OLs. Functional study demonstrated that its expression is essential for the differentiation of OLs, and promotes the outgrowth of OL membrane. Moreover, we found that the expression of Gltp is regulated by OL-lineage transcriptional factors, such as NKX2.2, OLIG2, SOX10, and MYRF. These findings provide important insights into the unrecognized functions of Gltp in OL differentiation and maturation. [ABSTRACT FROM AUTHOR]

Aim: This study identified discrepant therapeutic outcomes of antipsychotics. Methods: A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi‐ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables. Results: In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21–2.86), liver dysfunction (OR: 1.75–2.33), sedation (OR: 1.76–2.86), increased lipid level (OR: 2.04–2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14–0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45–20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09–0.11), and EPS (OR: 0.15–0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09–0.14), AIWG (OR = 0.44), sedation (OR: 0.33–0.47), and QTc prolongation (β = −2.17); ziprasidone related to higher risk of increased QT interval (β range: 3.11–3.22), nausea (OR: 3.22–3.91), lower risk of AIWG (OR: 0.27–0.46), liver dysfunction (OR: 0.41–0.38), and increased lipid level (OR: 0.41–0.55); haloperidol related to higher risk of EPS (OR: 2.64–6.29), hyperprolactinemia (OR: 5.45–9.44), and increased salivation (OR: 3.50–3.68). Perphenazine related to higher risk of EPS (OR: 1.89–2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi‐ancestry validation cohort. Conclusion: Future precision medicine should focus on personalized side‐effects. [ABSTRACT FROM AUTHOR]