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To enable personalized medicine, it is important yet highly challenging to accurately predict disease-causing mutations in target proteins at high throughput. Previous computational methods have been developed using evolutionary information in combination with various biochemical and structural features of protein residues to discriminate neutral vs. deleterious mutations. However, the power of these methods is often limited because they either assume known protein structures or treat residues independently without fully considering their interactions. To address the above limitations, we build upon recent progress in machine learning, network analysis, and protein language models, and develop a sequences-based variant site prediction workflow based on the protein residue contact networks: 1. We employ and integrate various methods of building protein residue networks using state-of-the-art coevolution analysis tools (RaptorX, DeepMetaPSICOV, and SPOT-Contact) powered by deep learning. 2. We use machine learning algorithms (Random Forest, Gradient Boosting, and Extreme Gradient Boosting) to optimally combine 20 network centrality scores to jointly predict key residues as hot spots for disease mutations. 3. Using a dataset of 107 proteins rich in disease mutations, we rigorously evaluate the network scores individually and collectively (via machine learning). This work supports a promising strategy of combining an ensemble of network scores based on different coevolution analysis methods (and optionally predictive scores from other methods) via machine learning to predict hotspot sites of disease mutations, which will inform downstream applications of disease diagnosis and targeted drug design. [ABSTRACT FROM AUTHOR]

The Longshou Shan, located in western China, plays a crucial role in connecting the Tarim Continent with the North China Craton. It provides valuable insights into the Cenozoic intracontinental deformation, the complex dynamics of Eurasian tectonics, and the relationship between the pre-Cenozoic Tethys and Central Asian orogenic systems. Consequently, comprehending the evolution of the Phanerozoic era in this region holds immense significance. Zircon (U-Th)/He (ZHe) dating was conducted on three granite samples (n = 18) collected from the Longshou Shan. The ZHe dates of these granite rocks range from 7.2 to 517.7 Ma, showing a negative correlation with eU values. Furthermore, a limestone sample from the Longshou Shan yielded ZHe (n = 4) ages of 172.0–277.1 Ma and AHe (n = 4) ages of 17–111.9 Ma. The area has undergone complex tectonic processes involving multiple phases of uplift and burial. Using both forward and inverse modeling methods, we aim to establish plausible thermal histories. Our models reveal: (1) Late Paleozoic unroofing; (2) Early Mesozoic cooling and Late Mesozoic regional stabilization; and (3) Cenozoic reheating and subsequent cooling. By investigating the intricate thermal history of the Longshou Shan through multi-method modeling, we compare different approaches and assess the capabilities of single ZHe dating for understanding a thermal history. This research contributes to unraveling the region's geological complexities and aids in evaluating various modeling methods. [ABSTRACT FROM AUTHOR]

• The Huangcheng basin has undergone three compression events since 100 Ma. • Slickenside analysis reveals north–south and east–west compression stresses. • Cretaceous sedimentary rocks in the area are sourced from the Qilian Shan-Nan Shan Block and Alashan Block. The sedimentary rocks in the Hexi Corridor, north-eastern Tibetan Plateau, contain information about crustal deformation during and after the closure of the Meso-Tethys Ocean and the growth of the Tibetan Plateau. This study examines the origin and deformation of Late Mesozoic sedimentary rocks in the Huangcheng basin where the source of Late Mesozoic sedimentary rocks and deformation styles of faults and folds remain controversial. Results from field mapping, fault kinematic analysis, and detrital zircon analysis suggest that the study region might have experienced three episodes of compression events since 100 Ma. The first episode is characterized by north–south compression, which could reflect the convergence between the Alashan and the Qilian Shan-Nan Shan. The second episode reflects the reactivation of the thrust faults related to the far-field effect resulting from the closure of the Neo-Tethys Ocean. The third episode is the regional east–west trending thrust due to the block extrusion. One set of slickensides indicates north–south compression while a second set implies nearly east–west compression, which could represent different stress orientations between the first two episodes and the third episode. Eleven detrital zircon samples from the Cretaceous to Neogene strata were collected for detrital zircon U-Pb dating and rare earth element analysis. Zircon U-Pb ages show major peaks around 265 Ma and 455 Ma with a notable lack of ages around 1.0 Ga. We infer that the source of the Neogene sedimentary rocks was the Qilian Shan while the sources of the Cretaceous sedimentary rocks were the Qilian Shan and Alashan. [ABSTRACT FROM AUTHOR]

• The Riganpei Co fault is divided into four segments based on the distribution of displacements. • The COPD within 0–30 m for each segment reveals that at least four large earthquakes ruptured this fault. • Reconstructed slip distribution shows a complex pattern of strong earthquake activities on different segments of the fault. High-resolution topographic datasets are useful for revealing offset features of fault geomorphology and are thus important for reconstructing the evolution history of faults. The Riganpei Co fault, located in the central Tibetan Plateau, is an important active fault on the northern boundary of the Bangong-Nujiang suture zone. In this study, WorldView-2 stereo images were used to generate high-resolution topographic data in a 1 km range on both flanks of the middle section of the Riganpei Co fault. We interpreted the tectonic geomorphology along the fault, classified it into distinct units, and measured the horizontal displacement of each unit. Within approximately 70 km along the fault, we obtained 396 displacement measurements ranging from 0 to 60 m. Given the evident uneven distribution of displacement, the fault was divided into four segments. In each fault segment, the reconstructed slip distributions revealed a tendency of larger displacements in the center and smaller displacements toward the ends. The cumulative offset probability distribution (COPD) of displacements displays 4–5 offset clusters in the range of 0–30 m for each segment, suggesting that at least four large earthquakes ruptured this fault. The binned COPD demonstrated that there are differences in the displacement accumulation modes among these fault segments, where the middle segment follows a characteristic slip accumulation mode. Reconstructed cumulative slip profiles revealed a complex pattern of strong earthquake activities along the Riganpei Co fault. [ABSTRACT FROM AUTHOR]

Active fault zones are areas impacted by intense tectonic activity, where geohazards such as landslides occur and their distribution characteristics vary across segments. Using the Litang fault zone in the eastern Tibetan Plateau as an example, this study cataloged landslides within a 10 km range on both sides of the fault zone. The Litang fault zone was divided into four sections based on landform characteristics and the spatial distribution of active faults. A comprehensive analysis was conducted on the relationship between landslide distribution and topography, lithology, and active faults in different sections. Additionally, the study employed a random forest model to compare landslide susceptibility between the whole-region and its sub-regions. The results show that lithology and topography significantly influence the distribution of landslide types. The Upper Triassic sandstone, Slate exhibit more debris flows in areas with slopes ranging from 5° to 35°, while slopes >35° in the Upper Triassic sandstone, Slate are prone to unstable slopes. Rock avalanche occur in Upper Triassic sandstone, Slate, and Quaternary sand and gravel. Active faults play a key role in control ling landslides distribution through distance, hanging wall, locked segment, and direction effects. The number of landslides is positively correlated with the activity of faults. Additionally, the dip angle and motion characteristics of faults have significant influence on the distribution of landslides. The results of landslide susceptibility evaluation show that sub-region models have higher accuracy than the whole-region model. This study provides a new method for exploring the spatial distribution of landslides and can provide scientific reference for reducing landslide disasters in active fault zones. • Landslides is significantly influenced by distance, hanging wall, locked section, and directionality of the active fault • Fault activity is positively correlated with landslide numbers, while the dip angle and motion affect distribution pattern • Sub-regional model can effectively reveal the spatial differences in landslide susceptibility along the active fault zone [ABSTRACT FROM AUTHOR]

Mibavademab (previously known as REGN4461), a fully human monoclonal antibody, is being investigated for the treatment of conditions associated with leptin deficiency. Here, we report pharmacokinetics (PKs), pharmacodynamics, and immunogenicity from a phase I study in healthy participants (NCT03530514). In part A, lean or overweight healthy participants were randomized to single‐ascending‐dose cohorts of 0.3, 1.0, 3.0, 10, and 30 mg/kg intravenous (i.v.), or 300 and 600 mg subcutaneous doses of mibavademab or placebo. In part B, overweight or obese participants were randomized to receive multiple doses of mibavademab (15 mg/kg i.v. loading dose and 10 mg/kg i.v. at weeks 3, 6, and 9) or placebo, stratified by body mass index and baseline leptin levels: low leptin (<5 ng/mL) or relatively low leptin (5–8 ng/mL in men and 5–24 ng/mL in women). Fifty‐six and 55 participants completed the single‐ascending‐dose and multiple‐dose parts, respectively. In the single‐ascending‐dose cohorts, mibavademab PKs were nonlinear with target‐mediated elimination, greater than dose‐proportional increases in exposure, and there were no dose‐dependent differences in total soluble leptin receptor (sLEPR) levels in serum over time. Following multiple‐dose administration of mibavademab in participants with leptin <8 ng/mL, lower mean mibavademab concentrations, higher mean total sLEPR concentrations, and larger mean decreases in body weight than in the relatively low leptin cohorts were observed. Baseline leptin was correlated with mibavademab PKs and pharmacodynamics. No treatment‐emergent anti‐mibavademab antibodies were observed in any mibavademab‐treated participant. Results from this study collectively inform further development of mibavademab to treat conditions associated with leptin deficiency. [ABSTRACT FROM AUTHOR]

In recent years, the rare earth doped upconversion luminescent materials have been widely used in many fields. In practical applications, we observed that various dopants have distinct effects on different substances to some extent. In this context, we have successfully synthesized a dual-mode-excited Ca3TeO6 double perovskite. After introduce the Yb3+/Er3+ ions pair, the designed phosphor can emit green and red luminescence under 980 nm and 1550 nm excitation, respectively, making it suitable for diverse scientific and technological applications. The potential up-conversion mechanisms driven by different excitation sources have been investigated. Moreover, it was discovered that adjusting the molar ratio of Er3+ and Yb3+ ions enhances the performance of the studied materials, rendering them well-suited for application as a high-quality optical thermometer based on the FIR technique. Our results clearly indicate that Er3+/Yb3+ co-doped Ca3TeO6 phosphors allows for multiple optimizations and control of material properties, showcasing great potential for applications in various field. [ABSTRACT FROM AUTHOR]

Font classification of oracle bone inscriptions serves as a crucial basis for determining the historical period to which they belong and holds significant importance in reconstructing significant historical events. However, conventional methods for font classification in oracle bone inscriptions heavily rely on expert knowledge, resulting in low efficiency and time-consuming procedures. In this paper, we proposed a novel recurrent graph neural network (R-GNN) for the automatic recognition of oracle bone inscription fonts. The proposed method used convolutional neural networks (CNNs) to perform local feature extraction and downsampling on oracle bone inscriptions. Furthermore, it employed graph neural networks (GNNs) to model the complex topologiure and global contextual information of oracle bone inscriptions. Finally, we used recurrent neural networks (RNNs) to effectively combine the extracted local features and global contextual information, thereby enhancing the discriminative power of the R-GNN. Extensive experiments on our benchmark dataset demonstrate that the proposed method achieves a Top-1 accuracy of 88.2%, significantly outperforming the competing approaches. The method presented in this paper further advances the integration of oracle bone inscriptions research and artificial intelligence. The code is publicly available at: https://github.com/yj3214/oracle-font-classification. [ABSTRACT FROM AUTHOR]

In this paper, a series of Sr0.96Al2Si2O8 phosphors doped with 0.02Eu2+ and 0.02Re3+ (where Re = Tm, Dy, Er, Nd, Sm, La, Ho) were synthesized using the high-temperature solid-phase method at 1350 °C for 4 hours. The samples underwent characterization for structural and phase analysis using XRD-6000. Fluorescence and photostimulated properties were evaluated with F-4600. The pyroluminescence curve indicates a trap depth of 0.6-0.8 eV for Sr0.96Al2Si2O8: 0.02Eu2+, 0.02Re3+ (where Re = Dy, Er, Sm, La, Ho), making it suitable for prolonged afterglow luminescence. In comparison with deep trap material Sr0.96Al2Si2O8: 0.02Eu2+, 0.02Nd3+, the generated traps approach or exceed 1 eV, suggesting its potential for use as a light excitation and optical storage material. Additionally, the correlation between sample TL and PSL was examined, confirming that the augmentation of initial photostimulated luminescence intensity is closely associated with the generation of new traps. Furthermore, considering the effect of different trivalent lanthanide rare earth ion doping on trap depth from a trap regulation perspective offers a potential avenue for elucidating the nuanced processes underlying photostimulated luminescence. [ABSTRACT FROM AUTHOR]

Cases of atopic dermatitis (AD)‐like rash induced by IL‐17A inhibitor secukinumab treatment (SI‐AD) have been recently reported in psoriasis patients. To identify immune and inflammatory factors expression in SI‐AD. A panel of 15 immune and inflammatory factors in peripheral blood samples from various groups, including patients with patients with SI‐AD, psoriasis with secukinumab (S‐stable), advanced psoriasis patients (Advanced) and healthy controls (HC). Interleukin‐10 (IL‐10), IL‐4 and IL‐17A were detected in skin tissue biopsy samples by immunohistochemistry and real‐time quantitative polymerase chain reaction. The immunoglobulin E levels in the SI‐AD patients exceeded normal values. The IL‐10 levels in SI‐AD patients were higher than those in S‐stable patients, advanced patients and HC. The IL‐4 levels in SI‐AD patients were higher than that in S‐stable patients and HC. The IL‐17A levels in SI‐AD patients were higher than those in advanced psoriasis patients and HC, but no significant differences were observed between SI‐AD patients and S‐stable patients. IL‐10 and IL‐4 levels were higher in AD‐like rashes than in healthy skin, while IL‐17A did not differ significantly between the two. Upon discontinuing secukinumab, and switching to oral cyclosporine, antihistamines, Janus kinase 1 inhibitor and topical glucocorticoids, SI‐AD patients experienced significant improvement in their skin lesions. Upon reexamination, all 15 immune and inflammatory factors returned to normal levels. Immune shift from Th17 towards Th2 may occur in SI‐AD, as indicated by abnormal expression of multiple immune and inflammatory factors observed in peripheral blood and skin tissues. [ABSTRACT FROM AUTHOR]

[Display omitted] A new catalyst system for the Heck reaction consisting of PdCl 2 and 2,6-bis(1,2,4-diazaphosphol-1-yl)pyridine as a ligand is proposed. This system is efficient for the coupling of styrene with aryl bromides (K 3 PO 4 , DMA, 130 °C) at 0.1 mol% catalyst loading. [ABSTRACT FROM AUTHOR]