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Abstract Alzheimer’s disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aβ-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aβ and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aβ and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aβ and pTau in 3xTg transgenic mice. It significantly eradicated Aβ plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aβ and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.

With the escalation of global climate change and human activity, geohazards become increasingly frequent which cause severe casualties and property losses to local communities. To alleviate this situation and provide scientific guidance for risk reduction, it is imperative to address some of the basic questions related to geohazards, including: i) how to detect active geohazards (AGs) rapidly and automatically over a wide area; ii) how to determine the region with a high level of hazard activity; iii) what are the primary conditioning factors (CFs) of AGs; and iv) do factors operate independently or are they interconnected. To tackle these issues, we propose a universally applicable framework for wide area automated detection of AGs. The framework is based on multi-source Earth observations which capture surface deformation ranging from millimeters to meters. Our study has focused on the Hexi Corridor (HXC) in Gansu Province, China, covering an area of 210,000 km2 with a length of 1100 km. First, we construct an AGs database for the HXC with high automatic and rapid update capabilities, including a total of 4492 AGs (3652 active landslides and 840 land subsidence areas). Second, using the Geographic Detectors method, we determine the primary CFs including elevation, land surface temperature, and precipitation. We find that faults exert greater control over very slow-moving landslides, but are less effective over slow-moving landslides. Third, we analyzed the interactive effects of dual CFs on geohazard actives. Any interaction effect of dual CFs contributes to the bivariate enhancement of geohazard activity. This study significantly enhances the capabilities of the wide area automated detection of AGs, and provides a crucial dataset for hazard prediction and mitigation along the HXC.

Emergency response after earthquakes, especially rapid access to building damage information, is of great significance to ensure timely rescue and reduce casualties. However, manual field surveys of building damages are inefficient and dangerous, and optical satellite data are more susceptible to cloud interference after earthquakes. Synthetic aperture radar (SAR) is now widely used in disaster response efforts due to its full-time and all-weather capability. According to the change in coherence between SAR images before and after earthquakes, it is possible to identify damaged buildings that cause coherence loss. However, the accuracy of traditional coherence-based damage detection methods is relatively low due to biases in coherence estimation and inconsistency in spatio-temporal baselines. In this study, we propose a new method to produce a postearthquake building damage proxy map (BDPM) based on multitemporal Sentinel-1 coherence, which incorporates homogeneous SAR pixel coherence estimation and histogram matching techniques. The former is used to reduce estimation biases and the latter to reduce the effect of baseline inconsistencies in adjacent coherence maps. We successfully applied this method to the 2022 Mw 6.2 Afghanistan earthquake, the 2023 strong earthquake sequence in Turkey, and the 2023 Ms 6.2 Jishishan, China earthquake. We also verified its accuracy (over 80%) by comparing the BDPM with results from the United Nations Institute for Training and Research and analyzed various factors affecting the distribution of damaged buildings. These analyses confirm the effectiveness of our method for generating BDPM using free medium-resolution Sentinel-1 data, which will greatly assist in earthquake emergency response.

Integrated geochemical, U-Pb zircon, and Pb isotopic data from granitoids of the Wulandele porphyry molybdenum deposit, northeastern Inner Mongolia, are reported to disclose the possible magmatic process and Mo ore-forming process. LA-ICP-MS zircon U-Pb dating constrains the timing of the quartz diorite and monzonitic granite to 282 ± 2.4 Ma and 135.4 ± 2.1 Ma, respectively. The ages are accordant with geological facts which state that the shallow Permian granitoids are only the ore-hosting rock while the concealed Cretaceous fine-grained granite is the causative intrusion. Whole-rock geochemical data show that the granitoids belong to the high-K calc-alkaline series, and are enriched in LILEs, but depleted in HSFEs. Permian granitoids exhibit I-type characteristics, while Cretaceous granite is akin to A-type granite. Pb isotopic ratios are consistent between Permian granitoids and Cretaceous granite with ratios of 206Pb/204Pb = 18.048–18.892, 207Pb/204Pb = 15.488–15.571, and 208Pb/204Pb = 37.066–38.441. Considering geological and geochemical features together, Permian granitoids are interpreted as subduction-related continental margin high-K calc-alkaline rocks, while Cretaceous granite may be the result of the remelting of the relic Permian arc in an extensional environment induced by the rollback of the Paleo-Pacific plate. Different from classical porphyry-type deposits, the Wulandele Mo deposit, which formed in an intraplate tectonic setting, indicates that the intraplate porphyry Mo deposit should be one of the important exploration targets in the Central Asian Orogenic Belt, especially its eastern segment.

Abstract Background The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. Objective We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). Methods We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X‐ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first‐attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. Results Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first‐attempt success rate of lead placement was obviously increased in CSV group (both p .05). Conclusion TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.