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DNA base editing technologies predominantly utilize engineered deaminases, limiting their ability to edit thymine and guanine directly. In this study, we successfully achieve base editing of both cytidine and thymine by leveraging the translesion DNA synthesis pathway through the engineering of uracil-DNA glycosylase (UNG). Employing structure-based rational design, exploration of homologous proteins, and mutation screening, we identify a Deinococcus radiodurans UNG mutant capable of effectively editing thymine. When fused with the nickase Cas9, the engineered DrUNG protein facilitates efficient thymine base editing at endogenous sites, achieving editing efficiencies up to 55% without enrichment and exhibiting minimal cellular toxicity. This thymine base editor (TBE) exhibits high editing specificity and significantly restores IDUA enzyme activity in cells derived from patients with Hurler syndrome. TBEs represent efficient, specific, and low-toxicity approaches to base editing with potential applications in treating relevant diseases., (© 2024. The Author(s).)

Fossil fuel (FF) CO 2 emissions account for the largest portion of human-related CO 2 emissions. It is essential to accurately understand the spatial distribution of high-resolution FFCO 2 emissions to formulate different carbon emission reduction policies in different regions. Therefore, a sectoral allocation approach was proposed to estimate FFCO 2 emissions in China from 2000 to 2021 based on multi-source data. Furthermore, the spatiotemporal characteristics of FFCO 2 emissions in different sectors were analyzed at different scales, and the spatial correlation of FFCO 2 emissions in the service sector and industrial sector was also evaluated through Moran's index. The results showed that the mean R 2 value of the sectoral allocation approach (0.89) exceeds that of the approach using only nighttime light (0.72). Moreover, the calculated results were utilized to analyze the Spatiotemporal variation of FFCO 2 emissions. The analysis revealed that China's FFCO 2 emissions increased from 3173 Mt in 2000-10662 Mt in 2021. The high emissions of FFCO 2 mainly come from the industrial sectors in North China and Central China, as well as the service sectors in the eastern coastal cities and other provincial capital cities. The spatial dependence of FFCO 2 emissions in the industrial sector was stronger than that in the service sector, but the spatial dependence of FFCO 2 emissions in the service sector showed an increasing trend from 2000 to 2021. These results have important references and implications for region-specific carbon emission reduction policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Long-term, high-resolution regional drought records contribute to understanding the impacts of drought on environmental and social systems in central China. Here, we develop a regional tree-ring width chronology of Pinus tabulaeformis Carr from the northern slope of Funiu Mountains on the north-south transition zone in central China. Monthly correlation analyses showed that temperature and humidity in current May and June are main limiting factors on tree growth. Despite that, the highest correlation with tree growth was found to be precipitation from previous December to current June (Pre DJ , 0.718, p < 0.001), which was chosen for reconstruction. The reconstructed Pre DJ revealed six drought periods and five wet periods over the past 220 years, and the recent dry spell would likely to continue. Spectral analyses indicated that the reconstructed Pre DJ was closely related to the El Nino-Southern Oscillation (ENSO, 2-7a) and 35a climatic oscillation of Bruckner, and was also affected by the Quasi-Biennial Oscillation (QBO). Wavelet analyses showed that the quasi-cycle of 2-7a persisted over the past 220 years and strengthened after the 1980s, and the QBO signals appeared from the 1860s to 1970s and wear off thereafter, and 35a cycle only appeared during 1820-1920. Spatial analysis found that the reconstructed Pre DJ had good spatial representation of precipitation in the central-eastern China. Therefore, the results of this study provide reliable information for understanding long-term drought impacts on environmental conditions and socioeconomic development in central China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A number of mitochondrial diseases in humans are caused by point mutations that could be corrected by base editors, but delivery of CRISPR guide RNAs into the mitochondria is difficult. In this study, we present mitochondrial DNA base editors (mitoBEs), which combine a transcription activator-like effector (TALE)-fused nickase and a deaminase for precise base editing in mitochondrial DNA. Combining mitochondria-localized, programmable TALE binding proteins with the nickase MutH or Nt.BspD6I(C) and either the single-stranded DNA-specific adenine deaminase TadA8e or the cytosine deaminase ABOBEC1 and UGI, we achieve A-to-G or C-to-T base editing with up to 77% efficiency and high specificity. We find that mitoBEs are DNA strand-selective mitochondrial base editors, with editing results more likely to be retained on the nonnicked DNA strand. Furthermore, we correct pathogenic mitochondrial DNA mutations in patient-derived cells by delivering mitoBEs encoded in circular RNAs. mitoBEs offer a precise, efficient DNA editing tool with broad applicability for therapy in mitochondrial genetic diseases., (© 2023. The Author(s).)

With the significant growth in the production and installation of photovoltaic (PV) systems, the recycling of end-of-life PV modules has become a critical concern. Thermal treatment is a promising approach to decompose all the polymer and separate different layers rapidly. However, the combustion of the backsheet can lead to the release of hazardous fluorinated compounds. This paper proposes a novel method combining low-temperature and thermal treatment to separate different layers in PV modules. This method leverages the back metallization of solar cells for PV module separation, providing a fresh separation perspective. The focus lies on investigating a low-temperature separation process, and the separation interfaces are characterized using SEM and EDS, shedding light on the separation position and physical separation mechanisms. Subsequently, the effects of different freezing temperatures, freezing times, and different laminated parts were investigated, and the processing parameters were optimized. Compared to direct thermal treatment, the proposed process eliminates the generation of hazardous fluorides and mitigates mass losses caused by thermal treatment effectively. This research provides valuable insights into the green and sustainable resource recovery of waste PV modules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Hydrogenolysis is an effective method for converting polyolefins into high-value chemicals. For the supported catalysts commonly used, the size of active metals is of great importance. In this study, it is discovered that the activity of CeO 2 -supported Ru single atom, nanocluster, and nanoparticle catalysts shows a volcanic trend in low-density polyethylene (LDPE) hydrogenolysis. Compared with CeO 2 supported Ru single atoms and nanoparticles, CeO 2 -supported Ru nanoclusters possess the highest conversion efficiency, as well as the best selectivity toward liquid alkanes. Through comprehensive investigations, the metal-support interactions (MSI) and hydrogen spillover effect are revealed as the two key factors in the reaction. On the one hand, the MSI is strongly related to the Ru surface states and the more electronegative Ru centers are beneficial to the activation of CH and CC bonds. On the other hand, the hydrogen spillover capability directly affects the affinity of catalysts and active H atoms, and increasing this affinity is advantageous to the hydrogenation of alkane species. Decreasing the Ru sizes can promote the MSI, but it can also reduce the hydrogen spillover effect. Therefore, only when the two effects achieve a balance, as is the case in CeO 2 -supported Ru nanoclusters, can the hydrogenolysis activity be promoted to the optimal value., (© 2023 Wiley-VCH GmbH.)

The Tongbai Mountains are an ecologically sensitive region to climate change, where there lies a climatic transitional zone from a subtropical to a warm−temperate monsoon climate. The northern boundary of Pinus taiwanensis Hayata is here; thus, climate information is well recorded in its tree rings. Based on developed earlywood width (EWW), latewood width (LWW) and total ring width (RW) chronologies (time period: 1887−2014 year) of Pinus taiwanensis Hayata in the Tongbai Mountains in central China, this paper analyzed characteristics of these chronologies and correlations between these chronologies and climate factors. The correlation results showed that earlywood width chronology contains more climate information than latewood width chronology and total ring width chronology, and mean temperature and mean maximum temperature in May−June were the main limiting factors for radial growth of Pinus taiwanensis Hayata. The highest significant value in all correlation analyses is −0.669 (p < 0.05) between earlywood width chronology and May−June mean temperature (TMJ) in the pre-mutation period (1958−2005) based on mutating in 2006. Thus, this paper reconstructed May−June mean temperature using earlywood width chronology from 1901 to 2005 (reliable period of earlywood width chronology is 1901−2014). The reconstructed May−June mean temperature experienced eight warmer periods and eight colder periods and also showed 2−3a cycle change over the past 105 years. The spatial correlation showed that the reconstructed series was representative of the May−June mean temperature variation in central and eastern China and significant positive/negative correlation with the sea surface temperature (SST) of the subtropical Pacific Ocean and the tropical Western Pacific Ocean and Indian Ocean from the previous October to the current June. This also indicated that May−June mean temperature periodic fluctuations might be related to the quasi-biennial oscillation (QBO) in the tropical Western Pacific Ocean and Indian Ocean. The results of this study have extended and supplemented the meteorological records of the Tongbai Mountains and have a guiding significance for forest tending and management in this area.

In order to adapt the development of vehicle driving automation technology for driving conditions under different levels of automation and based on the independently invented LF automatic pressure regulating valve (LF-APRV) for electronically controlled pneumatic brake systems (ECPBS), the dynamic PWM coupling pressure regulation method is proposed. This method realizes pressure regulation by adjusting the duty cycle of the control signal of the LF-APRV at different stages in the pressure regulation cycle. A co-simulation model was established to verify the feasibility of the method, and a test system was built to verify the correctness of the co-simulation model. Through the test, the pressure regulation performance of dynamic PWM coupling pressure regulation method and conventional on/off pressure regulation method was compared. The results show that the new method can improve the stability of pressure regulation, although the response time increases; under the new method, the overshoot of the pressure rising from 0 to 0.5 MPa was reduced by 69%, and the overshoot of the pressure decreasing from 0.5 MPa to 0.2 MPa was basically 0. Finally, tests and simulations showed that the dynamic PWM coupling pressure regulation method can meet the continuous graded braking requirements of vehicles, and the pressure response has good tracking performance on the target pressure.

Aiming at the engineering requirements of reducing the volume and improving the vibration characteristics of gears in the three-cylinder engine balanced system, a design and optimization method of gear structure is proposed based on the Design of Experiments (DOE) and proxy models. The paper analyzes the structure improvement process based on the gear design model and technical index requirements. By designing the plane characteristics of the weight-increasing module, the weight-reducing module and the elastic module, the calculation model of balance performance indices such as mass, moment of inertia and unbalance of new balanced vibration reduction gear are constructed. Then, a more efficient design method is proposed based on dynamic simulation and multidisciplinary optimization design platform (Isight). The results show that the new design method of gear structure can effectively reduce the structure improvement cycle. At the same time, the improved structure can reduce the thickness of the weight-increasing module by 6.3 mm and the vibration attenuation by more than 90%., Competing Interests: The authors have declared that no competing interests exist.

Background: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM., Main Body: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis., Conclusion: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

The Sanjiangyuan region is the source of the Yangtze, Yellow, and Lantsang rivers and is an important water conservation area in China. Due to the high altitude and cold climate in the region, the vegetation ecosystem has become very sensitive to environmental changes. In recent decades, due to the impact of climate change and human activities, the grassland degradation and desertification in this region have become very serious. In order to study the changes in aeolian desertification of grassland (ADG) in Sanjiangyuan, the Landsat images and GIS technology were used to monitor the dynamics of ADG from 1975 to 2015, and the driving factors behind this were analyzed. The results revealed that from 1975 to 2000, the area of ADG increased by 2855.8 km 2 , and the growth rate was 114.23 km 2  a -1 . In contrast, the ADG was restored from 2000 to 2015, with a decrease of 1286.54 km 2 and a rate of 85.77 km 2  a -1 . The main reasons for the expansion of ADG in the early stage were the rising temperature, the fluctuation of precipitation and wind speed, and the increase in intensified human activities. The main reasons for the reversal of ADG in the later stage were the warming and humidification of the climate, the reduction in wind speed, and the reduction in human activities and restoration of grassland caused by the ecological protection project.

Lots of research studies reveal that the surface atoms on the top/bottom facets of the nanosheets are the key features in enhancing electrocatalytic activity while the edge and corner sites of electrocatalysts often possess superior activity. Herein, we report 2D dendritic PdAgPt ternary nanoalloys with abundant crystal defects such as steps, twin boundary, and atomic holes, which can effectively work as catalytic active-sites. The morphology of PdAgPt nanoalloys can be regulated readily from dendritic nanosheets to nanowheels. Compared with binary Pd 68 Ag 32 nanodendrites, Pd 62 Pt 38 nanospheres, and Pt/C catalyst, the composition- and morphology-optimized Pd 43 Ag 21 Pt 36 nanowheels exhibit the best mass/specific activity and stability for methanol/ethanol oxidation reaction (MOR/EOR). The mass peak current density for EOR/MOR of Pd 43 Ag 21 Pt 36 is 7.08/3.50 times of the Pt/C catalyst. Simultaneously, the hydrogen evolution reaction performance of the Pd 43 Ag 21 Pt 36 nanowheels in terms of the lowest overpotential of 9 mv at a current density of 10 mA/cm 2 and high electrochemical stability is much better than that of binary Pd 68 Ag 32 nanodendrites, Pd 62 Pt 38 nanospheres, and Pt/C.

Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.

The combination of high-quality Al2 O3 dielectric and thiol chemistry passivation can effectively reduce the density of interface traps and Coulomb impurities, leading to a significant improvement of the mobility and a transition of the charge transport from the insulating to the metallic regime. A record high mobility of 83 cm(2) V(-1) s(-1) (337 cm(2) V(-1) s(-1) ) is reached at room temperature (low temperature) for monolayer WS2 . A theoretical model for electron transport is also developed., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)