The next-generation Open Targets Platform: reimagined, redesigned, rebuilt.

The Open Targets Platform (https://platform.opentargets.org/) is an open source resource to systematically assist drug target identification and prioritisation using publicly available data. Since our last update, we have reimagined, redesigned, and rebuilt the Platform in order to streamline data integration and harmonisation, expand the ways in which users can explore the data, and improve the user experience. The gene-disease causal evidence has been enhanced and expanded to better capture disease causality across rare, common, and somatic diseases. For target and drug annotations, we have incorporated new features that help assess target safety and tractability, including genetic constraint, PROTACtability assessments, and AlphaFold structure predictions. We have also introduced new machine learning applications for knowledge extraction from the published literature, clinical trial information, and drug labels. The new technologies and frameworks introduced since the last update will ease the introduction of new features and the creation of separate instances of the Platform adapted to user requirements. Our new Community forum, expanded training materials, and outreach programme support our users in a range of use cases.

The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage.

BACKGROUND: Chronic inflammation significantly contributes to photoreceptor death in blinding retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that act as key proinflammatory factors. We recently found the first-generation BET inhibitor JQ1 alleviated sodium iodate-induced retinal degeneration by suppressing cGAS-STING innate immunity. Here, we investigated the effects and mechanism of dBET6, a proteolysis­targeting chimera (PROTAC) small molecule that selectively degrades BET by the ubiquitin‒proteasome system, in light-induced retinal degeneration. METHODS: Mice were exposed to bright light to induce retinal degeneration, and the activation of cGAS-STING was determined by RNA-sequencing and molecular biology. Retinal function, morphology, photoreceptor viability and retinal inflammation were examined in the presence and absence of dBET6 treatment. RESULTS: Intraperitoneal injection of dBET6 led to the rapid degradation of BET protein in the retina without detectable toxicity. dBET6 improved retinal responsiveness and visual acuity after light damage (LD). dBET6 also repressed LD-induced retinal macrophages/microglia activation, Müller cell gliosis, photoreceptor death and retinal degeneration. Analysis of single-cell RNA-sequencing results revealed cGAS-STING components were expressed in retinal microglia. LD led to dramatic activation of the cGAS-STING pathway, whereas dBET6 suppressed LD-induced STING expression in reactive macrophages/microglia and the related inflammatory response. CONCLUSIONS: This study indicates targeted degradation of BET by dBET6 exerts neuroprotective effects by inhibiting cGAS-STING in reactive retinal macrophages/microglia, and is expected to become a new strategy for treatment of retinal degeneration.

Light damage induces inflammatory factors in mouse retina and vitreous humor.

Purpose: Increased inflammatory factor levels have been reported in the vitreous humor (VH) of diabetic retinopathy and neovascular age-related macular degeneration, ocular diseases generally associated with the formation of new retinal blood vessels and leakage. However, the levels of inflammatory mediators are less known in retinal degeneration without neovascularization. Human retinitis pigmentosa (RP) and animal models of light-induced retinal degeneration (LIRD) share several features, such as photoreceptor death and retinal inflammation. Here, we aimed to determine the levels of inflammatory factors in the VH of the LIRD mouse model. Methods: LIRD was induced by exposing BALB/c mice to white light (15,000 lx, 2 h), and the mice were recovered for 2 days before analysis (n = 50 mice). We assessed retinal morphology using optical coherence tomography and hematoxylin and eosin staining; retinal cell viability was determined using terminal deoxynucleotidyl transferase dUTP nick-end labeling, and retinal responses were measured based on electroretinogram signals. Total retinal RNAs were extracted and subjected to RNA sequencing analysis. VH samples from control (n = 4) and LIRD mice (n = 9) were assayed in triplicate for a panel of four inflammatory mediators using the Simple Plex Cartridge on an Ella System. Results: Retinal degeneration, photoreceptor death, infiltration of microglia/macrophages into the photoreceptor layer, and loss of a- and b-waves were obviously detected after LIRD. RNA sequencing revealed that light damage (LD) led to the significant upregulation of inflammatory factors in mouse retinas. In the VH, LD increased the total protein concentration. Dramatic induction of CCL2 (~3000 fold) and IL6 (~10 fold) was detected in VH in response to LD. Increased but not significant levels of TNFα and IL1ß were also detected in light-exposed VH. Conclusions: Given that the LIRD model mimics RP pathogenesis in some aspects, these results suggest a causative link between retinal degeneration and VH inflammation in RP progression, and the increased CCL2 level in VH may reflect similar elevated CCL2 expression in the degenerative retina.

Study on the Superlubricity Behavior of Ions under External Electric Fields at Steel Interfaces.

Realizing macroscopic superlubricity in the presence of external electric fields (EEFs) at the steel interfaces is still challenging. In this work, macroscopic superlubricity with a coefficient of friction value of approximately 0.008 was realized under EEFs with the lubrication of LiPF6-based ionic liquids at steel interfaces. The roles of cations and anions in the superlubricity realization under EEFs were studied. Based on the experimental results, the macroscopic superlubricity behavior of Li(PEG)PF6 under EEFs at steel interfaces is attributed to the strong hydration effect of Li+ cations and the complete reactions of anions that contributed to the formation of a boundary film on the appropriate surface. Moreover, the reduction in the number of iron oxides in the boundary film on the disc was beneficial for friction reduction. We also provide a calculation model to describe the relationship between the hydration effect and the optimal voltage position, at which the lowest friction might occur. Ultimately, this work proves that macroscopic superlubricity can be realized under EEFs at steel interfaces and provides a foundation for engineering applications of superlubricity in an electrical environment.

[LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis].

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Estimation of Soil Organic Carbon Content in the Ebinur Lake Wetland, Xinjiang, China, Based on Multisource Remote Sensing Data and Ensemble Learning Algorithms.

Soil organic carbon (SOC), as the largest carbon pool on the land surface, plays an important role in soil quality, ecological security and the global carbon cycle. Multisource remote sensing data-driven modeling strategies are not well understood for accurately mapping soil organic carbon. Here, we hypothesized that the Sentinel-2 Multispectral Sensor Instrument (MSI) data-driven modeling strategy produced superior outcomes compared to modeling based on Landsat 8 Operational Land Imager (OLI) data due to the finer spatial and spectral resolutions of the Sentinel-2A MSI data. To test this hypothesis, the Ebinur Lake wetland in Xinjiang was selected as the study area. In this study, SOC estimation was carried out using Sentinel-2A and Landsat 8 data, combining climatic variables, topographic factors, index variables and Sentinel-1A data to construct a common variable model for Sentinel-2A data and Landsat 8 data, and a full variable model for Sentinel-2A data, respectively. We utilized ensemble learning algorithms to assess the prediction performance of modeling strategies, including random forest (RF), gradient boosted decision tree (GBDT) and extreme gradient boosting (XGBoost) algorithms. The results show that: (1) The Sentinel-2A model outperformed the Landsat 8 model in the prediction of SOC contents, and the Sentinel-2A full variable model under the XGBoost algorithm achieved the best results R2 = 0.804, RMSE = 1.771, RPIQ = 2.687). (2) The full variable model of Sentinel-2A with the addition of the red-edge band and red-edge index improved R2 by 6% and 3.2% over the common variable Landsat 8 and Sentinel-2A models, respectively. (3) In the SOC mapping of the Ebinur Lake wetland, the areas with higher SOC content were mainly concentrated in the oasis, while the mountainous and lakeside areas had lower SOC contents. Our results provide a program to monitor the sustainability of terrestrial ecosystems through a satellite perspective.

Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome.

Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10-3 (95% CI 1.94 × 10-3 to 2.48 × 10-3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.

Multi-U-Net: Residual Module under Multisensory Field and Attention Mechanism Based Optimized U-Net for VHR Image Semantic Segmentation.

As the acquisition of very high resolution (VHR) images becomes easier, the complex characteristics of VHR images pose new challenges to traditional machine learning semantic segmentation methods. As an excellent convolutional neural network (CNN) structure, U-Net does not require manual intervention, and its high-precision features are widely used in image interpretation. However, as an end-to-end fully convolutional network, U-Net has not explored enough information from the full scale, and there is still room for improvement. In this study, we constructed an effective network module: residual module under a multisensory field (RMMF) to extract multiscale features of target and an attention mechanism to optimize feature information. RMMF uses parallel convolutional layers to learn features of different scales in the network and adds shortcut connections between stacked layers to construct residual blocks, combining low-level detailed information with high-level semantic information. RMMF is universal and extensible. The convolutional layer in the U-Net network is replaced with RMMF to improve the network structure. Additionally, the multiscale convolutional network was tested using RMMF on the Gaofen-2 data set and Potsdam data sets. Experiments show that compared to other technologies, this method has better performance in airborne and spaceborne images.

Very low-depth whole-genome sequencing in complex trait association studies.

MOTIVATION: Very low-depth sequencing has been proposed as a cost-effective approach to capture low-frequency and rare variation in complex trait association studies. However, a full characterization of the genotype quality and association power for very low-depth sequencing designs is still lacking. RESULTS: We perform cohort-wide whole-genome sequencing (WGS) at low depth in 1239 individuals (990 at 1× depth and 249 at 4× depth) from an isolated population, and establish a robust pipeline for calling and imputing very low-depth WGS genotypes from standard bioinformatics tools. Using genotyping chip, whole-exome sequencing (75× depth) and high-depth (22×) WGS data in the same samples, we examine in detail the sensitivity of this approach, and show that imputed 1× WGS recapitulates 95.2% of variants found by imputed GWAS with an average minor allele concordance of 97% for common and low-frequency variants. In our study, 1× further allowed the discovery of 140 844 true low-frequency variants with 73% genotype concordance when compared to high-depth WGS data. Finally, using association results for 57 quantitative traits, we show that very low-depth WGS is an efficient alternative to imputed GWAS chip designs, allowing the discovery of up to twice as many true association signals than the classical imputed GWAS design. AVAILABILITY AND IMPLEMENTATION: The HELIC genotype and WGS datasets have been deposited to the European Genome-phenome Archive (https://www.ebi.ac.uk/ega/home): EGAD00010000518; EGAD00010000522; EGAD00010000610; EGAD00001001636, EGAD00001001637. The peakplotter software is available at https://github.com/wtsi-team144/peakplotter, the transformPhenotype app can be downloaded at https://github.com/wtsi-team144/transformPhenotype. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Boosting the Quantum Efficiency of Ultralong Organic Phosphorescence up to 52 % via Intramolecular Halogen Bonding.

Ultralong organic phosphorescence (UOP) has attracted increasing attention due to its potential applications in optoelectronics, bioelectronics, and security protection. However, achieving UOP with high quantum efficiency (QE) over 20 % is still full of challenges due to intersystem crossing (ISC) and fast non-radiative transitions in organic molecules. Here, we present a novel strategy to enhance the QE of UOP materials by modulating intramolecular halogen bonding via structural isomerism. The QE of CzS2Br reaches up to 52.10 %, which is the highest afterglow efficiency reported so far. The crucial reason for the extraordinary QE is intramolecular halogen bonding, which can not only effectively enhance ISC by promoting spin-orbit coupling, but also greatly confine motions of excited molecules to restrict non-radiative pathways. This work provides a reasonable strategy to develop highly efficient UOP materials for practical applications.

Evaluating macroscopic sex estimation methods using genetically sexed archaeological material: The medieval skeletal collection from St John's Divinity School, Cambridge.

OBJECTIVES: In tests on known individuals macroscopic sex estimation has between 70% and 98% accuracy. However, materials used to create and test these methods are overwhelming modern. As sexual dimorphism is dependent on multiple factors, it is unclear whether macroscopic methods have similar success on earlier materials, which differ in lifestyle and nutrition. This research aims to assess the accuracy of commonly used traits by comparing macroscopic sex estimates to genetic sex in medieval English material. MATERIALS AND METHODS: Sixty-six individuals from the 13th to 16th century Hospital of St John the Evangelist, Cambridge, were assessed. Genetic sex was determined using a shotgun approach. Eighteen skeletal traits were examined, and macroscopic sex estimates were derived from the os coxae, skull, and os coxae and skull combined. Each trait was tested for accuracy to explore sex estimates errors. RESULTS: The combined estimate (97.7%) outperformed the os coxae only estimate (95.7%), which outperformed the skull only estimate (90.4%). Accuracy rates for individual traits varied: Phenice traits were most accurate, whereas supraorbital margins, frontal bossing, and gonial flaring were least accurate. The preauricular sulcus and arc compose showed a bias in accuracy between sexes. DISCUSSION: Macroscopic sex estimates are accurate when applied to medieval material from Cambridge. However, low trait accuracy rates may relate to differences in dimorphism between the method derivative sample and the St John's collection. Given the sex bias, the preauricular sulcus, frontal bossing, and arc compose should be reconsidered as appropriate traits for sex estimation for this group.

Liquid Superlubricity of Polyethylene Glycol Aqueous Solution Achieved with Boric Acid Additive.

Boric acid is a weak acid and has been used as a lubrication additive because of its special structure. In this study, we report that boric acid could achieve a robust superlubricity (µ < 0.01) as an additive in polyethylene glycol (PEG) aqueous solution at the Si3N4/SiO2 interfaces. The superlow and steady friction coefficient of approximately 0.004-0.006 could be achieved with boric acid under neutral conditions (pH of approximately 6.4), which is different from the acidic conditions leading to superlubricity. The influence of various factors, including boric acid concentration, sliding speed, applied load, PEG molecular weight, and the volume of lubricant on the superlubricity, were investigated. The results reveal that the PEG aqueous solution with the boric acid additive could achieve superlubricity under a wide range of conditions. The surface composition analysis shows that the synergy effect between boric acid and PEG provides sufficient H+ ions to realize the running-in process. Moreover, a composite tribochemical film composed of silica and ammonia-containing compounds were formed on the ball surface, contributing to the superlubricity. The film thickness calculation shows that superlubricity was achieved in a mixed lubrication region, and therefore, the superlubricity state was dominated by both the composite tribochemical film formed via the tribochemical reaction on the contact surfaces and the hydrodynamic lubricating film between the contact surfaces. Such a liquid superlubricity achieved under neutral conditions is of importance for both scientific understanding and engineering applications.

Superlubricity of 1-Ethyl-3-methylimidazolium trifluoromethanesulfonate Ionic Liquid Induced by Tribochemical Reactions.

The robust liquid superlubricity of a room-temperature ionic liquid induced by tribochemical reactions is explored in this study. Here, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM]TFS) could realize stable superlubricity (µ < 0.01) with water at the interfaces of Si3N4/SiO2. A superlow and steady friction coefficient of 0.002-0.004 could be achieved under neutral conditions (pH of 6.9 ± 0.1) after 600 s of running-in process. Various factors that could affect superlubricity were explored, including concentration of [EMIM]TFS, sliding speed, applied load, and volume of the lubricant. The results reveal that superlubricity can be achieved with [EMIM]TFS aqueous solution under a broad scope of conditions. The results of surface analysis show that a steady composite tribochemical layer comprising [EMIM]TFS, silica, ammonia-containing compounds, and sulfides was formed by tribochemical reactions between [EMIM]TFS and Si3N4 during the running-in period. The film thickness calculation reveals that the achieved superlubricity is in a mixed lubrication regime that comprises boundary lubrication and thin film lubrication. The superlubricity state is governed by a firm composite tribochemical layer, a molecular adsorption layer (electric double layer of [EMIM]TFS), and a fluid layer. The liquid superlubricity achieved by the ionic liquid is helpful for the development of new ionic liquids with superlubricity characteristics and is of great significance for scientific understanding as well as engineering applications.

The impacts of economy policy uncertainty on peer effects of firms R&D investment: Based on LDA machine learning and regression statistical modeling approach.

The Latent Dirichlet Allocation (LDA) model is used to extract the text themes of newspaper news and construct the Chinese Economic Policy Uncertainty (EPU) Index. On this basis, based on the relevant data of Chinese A-share listed companies from 2008 to 2020, this paper empirically analyzes the impact of EPU on peer effects of firms R&D investment, and finds that EPU will aggravate the peer effects of firms R&D investment. Furthermore, the moderating effect of manager's motivation to maintain reputation on the process of EPU influencing the peer effects of firms R&D investment was tested, and the mechanism of EPU influencing the peer effects of firms R&D investment through financial frictions was verified.

Responses of vegetation cover to hydro-climatic variations in Bosten Lake Watershed, NW China.

Amidst the backdrop of global climate change, it is imperative to comprehend the intricate connections among surface water, vegetation, and climatic shifts within watersheds, especially in fragile, arid ecosystems. However, these relationships across various timescales remain unclear. We employed the Ensemble Empirical Mode Decomposition (EEMD) method to analyze the multifaceted dynamics of surface water and vegetation in the Bosten Lake Watershed across multiple temporal scales. This analysis has shed light on how these elements interact with climate change, revealing significant insights. From March to October, approximately 14.9-16.8% of the areas with permanent water were susceptible to receding and drying up. Both the annual and monthly values of Bosten Lake's level and area exhibited a trend of initial decline followed by an increase, reaching their lowest point in 2013 (1,045.0 m and 906.6 km2, respectively). Approximately 7.7% of vegetated areas showed a significant increase in the Normalized Difference Vegetation Index (NDVI). NDVI volatility was observed in 23.4% of vegetated areas, primarily concentrated in the southern part of the study area and near Lake Bosten. Regarding the annual components (6 < T < 24 months), temperature, 3-month cumulative NDVI, and 3-month-leading precipitation exhibited the strongest correlation with changes in water level and surface area. For the interannual components (T≥ 24 months), NDVI, 3-month cumulative precipitation, and 3-month-leading temperature displayed the most robust correlation with alterations in water level and surface area. In both components, NDVI had a negative impact on Bosten Lake's water level and surface area, while temperature and precipitation exerted positive effects. Through comparative analysis, this study reveals the importance of temporal periodicity in developing adaptive strategies for achieving Sustainable Development Goals in dryland watersheds. This study introduces a robust methodology for dissecting trends within scale components of lake level and surface area and links these trends to climate variations and NDVI changes across different temporal scales. The inherent correlations uncovered in this research can serve as valuable guidance for future investigations into surface water dynamics in arid regions.

Oligomeric organization of membrane proteins from native membranes at nanoscale spatial and single-molecule resolution.

The oligomeric organization of membrane proteins in native cell membranes is a critical regulator of their function. High-resolution quantitative measurements of oligomeric assemblies and how they change under different conditions are indispensable to understanding membrane protein biology. We report Native-nanoBleach, a total internal reflection fluorescence microscopy-based single-molecule photobleaching step analysis technique to determine the oligomeric distribution of membrane proteins directly from native membranes at an effective spatial resolution of ~10 nm. We achieved this by capturing target membrane proteins in native nanodiscs with their proximal native membrane environment using amphipathic copolymers. We applied Native-nanoBleach to quantify the oligomerization status of structurally and functionally diverse membrane proteins, including a receptor tyrosine kinase (TrkA) and a small GTPase (KRas) under growth-factor binding and oncogenic mutations, respectively. Our data suggest that Native-nanoBleach provides a sensitive, single-molecule platform to quantify membrane protein oligomeric distributions in native membranes under physiologically and clinically relevant conditions.

Genetic history of Cambridgeshire before and after the Black Death.

The extent of the devastation of the Black Death pandemic (1346-1353) on European populations is known from documentary sources and its bacterial source illuminated by studies of ancient pathogen DNA. What has remained less understood is the effect of the pandemic on human mobility and genetic diversity at the local scale. Here, we report 275 ancient genomes, including 109 with coverage >0.1×, from later medieval and postmedieval Cambridgeshire of individuals buried before and after the Black Death. Consistent with the function of the institutions, we found a lack of close relatives among the friars and the inmates of the hospital in contrast to their abundance in general urban and rural parish communities. While we detect long-term shifts in local genetic ancestry in Cambridgeshire, we find no evidence of major changes in genetic ancestry nor higher differentiation of immune loci between cohorts living before and after the Black Death.

[Advances of the novel immunosuppressant brasilicardin A].

Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete Nocardia brasiliensis IFM 0406 with highly potent immunosuppressive activity (IC50=0.057 µg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.

Investigation of the spatial and temporal variation of soil salinity using Google Earth Engine: a case study at Werigan-Kuqa Oasis, West China.

Large-scale soil salinity surveys are time-costly and labor-intensive, and it is also more difficult to investigate historical salinity, while in arid and semi-arid regions, the investigation of the spatial and temporal characteristics of salinity can provide a scientific basis for the scientific prevention of salinity, With this objective, this study uses multi-source data combined with ensemble learning and Google Earth Engine to build a monitoring model to observe the evolution of salinization in the Werigan-Kuqa River Oasis from 1996 to 2021 and to analyze the driving factors. In this experiment, three ensemble learning models, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM), were established using data collected in the field for different years and some environmental variables, After the accuracy validation of the model, XGBoost had the highest accuracy of salinity prediction in this study area, with RMSE of 17.62 dS m-1, R2 of 0.73 and RPIQ of 2.45 in the test set. In this experiment, after Spearman correlation analysis of soil Electrical Conductivity (EC) with environmental variables, we found that the near-infrared band in the original band, the DEM in the topographic factor, the vegetation index based on remote sensing, and the salinity index soil EC had a strong correlation. The spatial distribution of salinization is generally characterized by good in the west and north and severe in the east and south. Non-salinization, light salinization, and moderate salinization gradually expanded southward and eastward from the interior of the western oasis over 25 years. Severe and very severe salinization gradually shifted from the northern edge of the oasis to the eastern and southeastern desert areas during the 25 years. The saline soils with the highest salinity class were distributed in most of the desert areas in the eastern part of the Werigan-Kuqa Oasis study area as well as in smaller areas in the west in 1996, shrinking in size and characterized by a discontinuous distribution by 2021. In terms of area change, the non-salinized area increased from 198.25 in 1996 to 1682.47 km2 in 2021. The area of saline soil with the highest salinization level decreased from 5708.77 in 1996 to 2246.87 km2 in 2021. overall, the overall salinization of the Werigan-Kuqa Oasis improved.

Determination of oligomeric organization of membrane proteins from native membranes at nanoscale-spatial and single-molecule resolution.

The oligomeric organization of membrane proteins in native cell membranes is a critical regulator of their function. High-resolution quantitative measurements of oligomeric assemblies and how they change under different conditions are indispensable to the understanding of membrane protein biology. We report a single-molecule imaging technique (Native-nanoBleach) to determine the oligomeric distribution of membrane proteins directly from native membranes at an effective spatial resolution of ∼10 nm. We achieved this by capturing target membrane proteins in "native nanodiscs" with their proximal native membrane environment using amphipathic copolymers. We established this method using structurally and functionally diverse membrane proteins with well-established stoichiometries. We then applied Native-nanoBleach to quantify the oligomerization status of a receptor tyrosine kinase (TrkA) and a small GTPase (KRas) under conditions of growth-factor binding or oncogenic mutations, respectively. Native-nanoBleach provides a sensitive, single-molecule platform to quantify membrane protein oligomeric distributions in native membranes at an unprecedented spatial resolution.