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Axially chiral biaryl motifs possessing ortho -heteroatom-substituted functionalities exist widely in the structures of natural products and have served as foundation for constructing prominent chiral organocatalysts, ligands, functional materials, and even bioactive molecules. However, a general and enantioselective synthesis of such chiral structures with high synthetic value is rare. Taking advantage of the BaryPhos-facilitated asymmetric Suzuki-Miyaura cross-coupling, we have established a general, efficient and enantioselective construction of the ortho sulfur- or nitrogen-substituted axially chiral biaryls. The protocol shows excellent compatibility to various functional groups and structural features, delivering chiral biaryl structures with ortho -sulfonyl groups or with ortho -nitro groups at a broad range of molecular diversity and complexity. The immobilization of BaryPhos on polyethylene glycol (PEG) support has enabled homogeneous enantioselective cross-coupling in aqueous media and the palladium catalyst recycling for multiple times. The method has enabled a concise 10-step asymmetric synthesis of isoplagiochin D as well as the construction of chiroptical molecules with circularly polarized luminescence (CPL) properties. Ortho-heteroatom-substituted axially chiral biaryls are valuable structures in synthetic and medicinal chemistry. Here, the authors established an efficient synthesis of these chiral structures via asymmetric cross-coupling.

The China Meteorological Forcing Dataset (CMFD) is the first high spatial-temporal resolution gridded near-surface meteorological dataset developed specifically for studies of land surface processes in China. The dataset was made through fusion of remote sensing products, reanalysis datasets and in-situ station data. Its record begins in January 1979 and is ongoing (currently up to December 2018) with a temporal resolution of three hours and a spatial resolution of 0.1°. Seven near-surface meteorological elements are provided in the CMFD, including 2-meter air temperature, surface pressure, and specific humidity, 10-meter wind speed, downward shortwave radiation, downward longwave radiation and precipitation rate. Validations against observations measured at independent stations show that the CMFD is of superior quality than the GLDAS (Global Land Data Assimilation System); this is because a larger number of stations are used to generate the CMFD than are utilised in the GLDAS. Due to its continuous temporal coverage and consistent quality, the CMFD is one of the most widely-used climate datasets for China. Measurement(s) temperature • pressure • humidity • atmospheric wind speed • radiation • precipitation process Technology Type(s) digital curation Factor Type(s) geographic location • time Sample Characteristic - Environment climate system Sample Characteristic - Location China Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.11558439

Chiral N -heterocycles such as piperidines and tetrahydroisoquinolines are privileged structural motifs in drug discovery and pharmaceutical industry. The development of efficient and practical asymmetric synthetic methods towards pharmaceutically important chiral N -heterocycles constitutes an important subject in synthetic chemistry. Asymmetric synthesis of 2,3- cis -disubstituted piperidines bearing two consecutive chiral centers is particularly challenging in terms of both diastereoselective and enantioselective control. In this work, a regiospecific and enantioselective cyclizative aminoboration is designed to tackle this problem by employing Cu/( S , S )-Ph-BPE as the chiral catalyst, leading to a series of 2,3- cis -disubstituted piperidines as well as C1-substituted tetrahydroisoquinolines in moderate to good yields and excellent enantioselectivities. The asymmetric six-membered ring-closing aminoboration features a broad substrate scope, mild reaction conditions, and excellent functional group compatibility. DFT calculation reveals the importance of noncovalent interactions between substrate and Cu catalyst in controlling the enantioselectivity. The synthetic utility and practicality of this cyclization protocol have been exemplified by the synthesis of the key chiral intermediates of avacopan and L-733,060. Chiral N-heterocycles such as piperidines and tetrahydroisoquinolines are privileged structural motifs in drug discovery and pharmaceutical industry. Here, the authors report a regiospecific and enantioselective cyclizative aminoboration leading to a series of 2,3-cis-disubstituted piperidines as well as C1-substituted tetrahydroisoquinolines under copper catalytic conditions.

Amyloid fibril is an important pharmaceutical target for diagnostic and therapeutic treatment of neurodegenerative diseases. However, rational design of chemical compounds that interact with amyloid fibrils is unachievable due to the lack of mechanistic understanding of the ligand–fibril interaction. Here we used cryoelectron microscopy to survey the amyloid fibril-binding mechanism of a series of compounds including classic dyes, (pre)clinical imaging tracers and newly identified binders from high-throughput screening. We obtained clear densities of several compounds in complex with an α-synuclein fibril. These structures unveil the basic mechanism of the ligand–fibril interaction, which exhibits remarkable difference from the canonical ligand–protein interaction. In addition, we discovered a druggable pocket that is also conserved in the ex vivo α-synuclein fibrils from multiple system atrophy. Collectively, these findings expand our knowledge of protein–ligand interaction in the amyloid fibril state, which will enable rational design of amyloid binders in a medicinally beneficial way. Tao et al. reported a series of cryo-EM structures of α-synuclein fibrils in complex with amyloid dyes and imaging tracers, and identified druggable pockets in the fibrils of multiple system atrophy.

Star sensors undergo laboratory calibration before they leave the factory. In addition, recalibration is necessary after they experience vibration, deformation, etc. Using the analysis of attitude-dependent and attitude-independent interstar angular invariance calibration methods (IAICMs) as a reference, an attitude-correlated frame-based calibration method (ACFCM) is proposed in this work, which combines the advantages of both methods. Using outdoor star observations, the ACFCM correlates star image frames obtained at different times via a strapdown gyro unit. As a result, the number of efficient star images for calibration increases rapidly and the distribution of star images becomes much more uniform, thus improving the calibration accuracy of the star sensor. A simulation and experimental tests were designed and carried out. Both the simulation and experimental results verify the feasibility of the proposed ACFCM method. Furthermore, by comparing our method with the IAICMs, the repeatability and reliability of the principal point obtained from the calibration with the ACFCM method proposed in this work were significantly improved.

Quadruped robots, an important class of unmanned aerial vehicles, have broad potential for applications in education, service, industry, military, and other fields. Their independent positioning plays a key role for completing assigned tasks in a complex environment. However, positioning based on global navigation satellite systems (GNSS) may result in GNSS jamming and quadruped robots not operating properly in environments sheltered by buildings. In this paper, a tightly coupled LiDAR vision inertial odometer (LVIO) is proposed to address the positioning inaccuracy of quadruped robots, which have poor mileage information obtained though legs and feet structures only. With this optimization method, the point cloud data obtained by 3D LiDAR, the image feature information obtained by binocular vision, and the IMU inertial data are combined to improve the precise indoor and outdoor positioning of a quadruped robot. This method reduces the errors caused by the uniform motion model in laser odometer as well as the image blur caused by rapid movements of the robot, which can lead to error-matching in a dynamic scene; at the same time, it alleviates the impact of drift on inertial measurements. Finally, the quadruped robot in the laboratory is used to build a physical platform for verification. The experimental results show that the designed LVIO effectively realizes the positioning of four groups of robots with high precision and strong robustness, both indoors or outdoors, which verify the feasibility and effectiveness of the proposed method.

This study investigates the stratification of soil thermal properties induced by soil organic carbon (SOC) and its impacts on the parameterization of the thermal properties. Soil parameters were measured for alpine grassland stations and North China flux stations, with a total of 34 stations and 77 soil profiles. Measured data indicate that the topsoils of alpine grasslands contain high SOC contents than underlying soil layers, which leads to higher soil porosity values and lower thermal conductivity and bulk density values in the topsoils. However, this stratification is not evident at the lowland stations due to low SOC contents. Evaluations against measured data show that three thermal conductivity schemes used in land surface models severely overestimate the values for soils with high SOC content (i.e. topsoils of alpine grassland), but they are better for soils with low SOC content. A new parameterization is then developed to take the impacts of SOC into account. The new one can well estimate the soil thermal conductivity values in both low and high SOC content cases, and therefore, it is a potential candidate of thermal conductivity scheme to be used in land surface models.

Background Non-small cell lung cancer (NSCLC) patients often develop resistance to first-line etoposide/cisplatin (EP) chemotherapy. However, available studies only focus on single-agent resistance to either etoposide or cisplatin in NSCLC. Hence, a notable knowledge gap exists in terms of the mechanisms underlying multidrug resistance, particularly within a system that recapitulates EP resistance in NSCLC. This emphasizes an urgent need for new strategies to tackle this challenge. Methods This study established a chemotherapy-resistant xenograft mouse model that mimicked the clinical chemotherapy regimens used for patients with NSCLC and aimed to explore the molecular mechanisms that contribute to chemotherapy resistance in NSCLC. The key protein that regulates chemotherapy resistance in NSCLC were identified through proteomics and co-immunoprecipitation mass spectrometry (Co-IP/MS) analyses, and revealed its regulatory mechanisms. Results This study identified glutamine-fructose-6-phosphate transaminase 2 (GFAT2,) as a key driver of resistance, upregulated in chemoresistant NSCLC cells. GFAT2 critically regulates the hexosamine biosynthetic pathway (HBP), enhancing uridine diphosphate-GlcNAc (UDP-GlcNAc) synthesis and overall O-GlcNAcylation. Specifically, GFAT2 augments O-GlcNAcylation of heat shock protein family D member 1 (HSPD1) at residue T320. This modification stabilizes HSPD1 by blocking its tripartite motif containing 21 (TRIM21)-mediated ubiquitination and degradation. Stabilized HSPD1 subsequently activates anti-apoptotic signaling, promoting cell survival during chemotherapy. Crucially, knockdown of either GFAT2 or HSPD1 restored chemosensitivity in models. Conclusions These findings elucidate the GFAT2/HSPD1 axis and O-GlcNAcylation as pivotal metabolic mechanisms underlying EP resistance, identifying them as promising therapeutic targets to overcome chemoresistance in NSCLC.

Solar radiation over the Tibetan Plateau has declined over recent three decades, whereas total cloud cover has a decreasing trend. A likely explanation to this paradox is the increase in aerosols over this clean region. However, this study shows that the radiation extinction due to aerosol loading is of one order lower in magnitude than the observed dimming, and the solar dimming is also seen in a satellite product that was produced without considering temporal variations of aerosols. Instead, the inter‐annual variability and decadal change in solar radiation is contrasting to that in water vapor amount and deep cloud cover (but not total cloud cover). Therefore, we suggest that the solar dimming over the Plateau is mainly due to the increase in water vapor amount and deep cloud cover, which in turn are related to the rapid warming and the increase in convective available potential energy. Key Points Solar dimming and total cloud cover decreasing co‐existed Aerosol impact on solar dimming was not significant over TP Deep cloud cover and water vapor content increased

Indian monsoon circulation is the primary driver of the long‐range transboundary mercury (Hg) pollution from South Asia to the Himalayas and Tibet Plateau region, yet the northward extent of this transport remains unknown. In this study, a strong δ202Hg signature overlapping was found between Lake Gokyo and Indian anthropogenic sources, which is an indicative of the Hg source regions from South Asia. Most of the sediment samples were characterized with relatively large positive Δ199Hg values (mean = 0.07‰–0.44‰) and small positive Δ200Hg values (mean = 0.03‰–0.08‰). Notably, the Δ199Hg values in the lake sediments progressively increased from southwest to northeast. Moreover, the Δ199Hg values peaked at Lake Tanglha (mean = 0.44‰ ± 0.04‰) before decreased at Lake Qinghai that is under the influence of the westerlies. Our results suggest that transboundary atmospheric transport could transport Hg from South Asia northwards to at least the Tanglha Mountains in the northern Himalaya‐Tibet. Plain Language Summary The fragile ecosystems of the Himalayas and Tibet Plateau region have been suffering transboundary Hg pollution from South Asia. However, the northward extent of this transport of atmospheric Hg pollution remains poorly understood. In our study, sediment core Hg isotope compositions from four lakes (Gokyo, Namco, and Tanglha in the south of the Tanglha Mountains and Qinghai in the north) along a southwest‐northeast transect in the region were combined to constrain the northward extent of transboundary Hg pollution by examining both mass‐dependent and mass‐independent fractionations. Our results suggest that transboundary atmospheric transport could transport Hg from South Asia northwards to at least the Tanglha Mountains in the northern Himalaya‐Tibet. Key Points The δ202Hg signatures among the three lakes in the north are indistinguishable without spatial distribution differences Most of sediment samples were characterized by positive Δ199Hg and Δ200Hg values The northward extent of atmospheric mercury transboundary transport could be anchored by progressive shifts of Δ199Hg signatures