Unveiling the role of IGF1R in autism spectrum disorder: a multi-omics approach to decipher common pathogenic mechanisms in the IGF signaling pathway

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Research on the technology of casing inspection through tubing in the Saertu Development Zone of Daqing Oilfield

With the further development of Daqing Oilfield, the occurrence of widespread casing damage in the Saertu Development Area has been on the rise annually.In order to promptly prevent, detect and address casing damage, the management departments of the oil extraction plants must schedule regular casing inspection operations. This approach not only raises production costs but also prolongs the well shutdown period, further impacting crude oil output.This article focuses on the technical needs of oilfield development and has developed tubing and casing detection technology, the radial magnetic scanning system is integrated with the sixteen arm wellbore diameter, the synchronous tubing and casing inspection instrument represents the latest in concurrent inspection technology, developed specifically for the technical demands of oilfield development Without displacing the tubing column, it simultaneously captures data on tubing inner diameter, tubing continuity, the extent of casing damage via magnetic scanning, and continuous 3D imaging of the tubing at standard inspection speeds, the workload of checking and matching tasks were significantly reduced. Between 2022 and 2023, the through-tubing casing inspection technology was utilized in 525 wells, with 356 wells verified by mobilizing the tubing column, achieving a predictive accuracy of 87.6% and generating economic benefits of 69.6 million yuan

Analysis of Carbon Storage and Its Contributing Factors—A Case Study in the Loess Plateau (China)

The Chinese Loess Plateau is an ecologically fragile and sensitive area. The carbon storage dynamics in this region and the contributions from land use/land cover change (LUCC) and carbon density from 2000 to 2010 were analyzed in this paper. Normalized difference vegetation index (NDVI), biomass and soil carbon data in 2000 were used for regression analysis of biomass and soil carbon, and an inversion analysis was used to estimate biomass and soil carbon in 2005 and 2010. Quadrat data, including aboveground biomass and soil organic carbon, were used to calibrate the model output. Carbon storage and sequestration were calculated by the InVEST toolset with four carbon pools, including aboveground biomass, belowground biomass, dead wood and soil carbon. The results showed that carbon storage increased steadily from 2000 to 2010, increasing by 0.260 billion tons, and that woodland area increased and arable land decreased; the overall trend in land cover improved, but the improvement was not pronounced. Carbon storage in the Loess Plateau was correlated with geographical factors. We found that when assuming a constant carbon density, carbon storage decreased, accounting for &minus;1% of the carbon storage dynamics. When assuming no land conversion, carbon storage increased, accounting for 101% of the carbon storage dynamics

A Fast Simulation Approach to the Thermal Recovery Characteristics of Deep Borehole Heat Exchanger after Heat Extraction

Necessary intermittence after heat extraction for a deep borehole heat exchanger (DBHE) is beneficial for sustainable operation. This paper centers on the fast simulation for thermal recovery characteristics of DBHE under intermittent condition. First of all, in view of the existing temperature gradient and multi-layer heterogeneity of rock underground that could never be ignored for DBHE, we extend the classical finite line source model based on heat source theory and superposition principle to account for the vertical heat flux distribution varying along depth and heterogeneous thermal conductivities in the multi-layer rock zone. Moreover, a fast simulation approach for heat transfer analysis inside the borehole coupled with the extended finite line source model is put forward to depict the transient thermal response and dynamic thermal recovery of rock outside borehole. To the authors’ knowledge, no such algorithm for deep BHE has yet been suggested in the previous literature. This approach has proven to be reliable and efficient enough for DBHE simulation under the intermittent condition. Simulation results show that at least 65 days of intermittence for the model in study should be spared after the heating season to achieve sustainable heat extraction in the next cyclic operation. Compared to the detailed solution based on full discretization numerical schemes, the relative error for borehole bottom temperature was 0.79%. In addition, comparison of the simulation results for thermal performance during the heating season in a three-year cyclic operation with 205 days intermittence shows that both the outflow temperature and heat extraction rate in the subsequent cycle after intermittence are in good agreement with the full 3D numerical solution in the reference (with a relative error of 6.36% for the outflow temperature and 9.3% for the heat extraction rate). Regarding the calculation speed, around a 13 times acceleration can be achieved. Finally, it is also promising to be applicable for thermal recovery simulation after heat extraction of vertical closed loop borehole heat exchangers at arbitrary length from shallow to deep.</jats:p

Impacts of Water and Sediment Fluxes into the Sea on Spatiotemporal Evolution of Coastal Zone in the Yellow River Delta

Water and sediment fluxes into the sea are the basis for the stability of the ecological pattern of the Yellow River Delta (YRD). As a Ramsar wetland of international importance, the YRD is facing the huge ecological risk of land degradation due to changes in water&ndash;sediment fluxes into the sea. In this study, we investigated the spatiotemporal dynamics of the coastline and subaerial delta using annual remote sensing images and revealed more detailed and clear relationships between water&ndash;sediment fluxes into the sea and the YRD evolution, including the whole delta and its subregions (e.g., the Qingshuigou and Diaokou regions) from 1976 to 2022. Our results showed that the mean yearly water and sediment fluxes during the study period amounted to 210.50 &times; 108 m3 yr&minus;1 and 367.81 Mt yr&minus;1, respectively. There was an abrupt change in water and sediment fluxes into the sea in 1999, and both decreased significantly from 1976 to 1999, whereas the water discharge has significantly increased and the sediment flux has stabilized since around 2000. The delta area evolutions of the whole YRD and the Qingshuigou region can be characterized by three stages: a rapid growth stage (1976&ndash;1993), a rapid retreat stage (1993&ndash;2002), and a gradual recovery stage (2002&ndash;2022). The area in the Diaokou region displayed a continuous decreasing trend from 1976 to 2022. The regression analysis indicated that the relationships between cumulative sediment flux and cumulative land accretion area presented spatiotemporal differentiation. The cumulative land accretion area increased with the cumulative sediment flux in the whole YRD and its subregions from 1976 to 1992, decreased with the cumulative sediment flux in the YRD from 1993 to 2002, except for the northeast of Qingshuigou, and then expanded with the cumulative sediment flux in the YRD from 2003 to 2022, except for the southeast of Qingshuigou