Identification of shared molecular mechanisms and diagnostic biomarkers between heart failure and idiopathic pulmonary fibrosis.

Background: Heart failure (HF) and idiopathic pulmonary fibrosis (IPF) are global public health concerns. The relationship between HF and IPF is widely acknowledged. However, the interaction mechanisms between these two diseases remain unclear, and early diagnosis is particularly difficult. Through the integration of bioinformatics and machine learning, our work aims to investigate common gene features, putative molecular causes, and prospective diagnostic indicators of IPF and HF. Methods: The Gene Expression Omnibus (GEO) database provided the RNA-seq datasets for HF and IPF. Utilizing a weighted gene co-expression network analysis (WGCNA), possible genes linked to HF and IPF were found. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were then employed to analyze the genes that were shared by HF and IPF. Using the cytoHubba and iRegulon algorithms, a competitive endogenous RNA (ceRNA) network was built based on seven basic diagnostic indicators. Additionally, hub genes were identified using machine learning approaches. External datasets were used to validate the findings. Lastly, the association between the number of immune cells in tissues and the discovered genes was estimated using the CIBERSORT method. Results: In total, 63 shared genes were identified between HF- and IPF-related modules using WGCNA. Extracellular matrix (ECM)/structure organization, ECM-receptor interactions, focal, and protein digestion and absorption, were shown to be the most enrichment categories in GO and KEGG enrichment analysis of common genes. Furthermore, a total of seven fundamental genes, including COL1A1, COL3A1, THBS2, CCND1, ASPN, FAP, and S100A12, were recognized as pivotal genes implicated in the shared pathophysiological pathways of HF and IPF, and TCF12 may be the most important regulatory transcription factor. Two characteristic molecules, CCND1 and NAP1L3, were selected as potential diagnostic markers for HF and IPF, respectively, using a support vector machine-recursive feature elimination (SVM-RFE) model. Furthermore, the development of diseases and diagnostic markers may be associated with immune cells at varying degrees. Conclusions: This study demonstrated that ECM/structure organisation, ECM-receptor interaction, focal adhesion, and protein digestion and absorption, are common pathogeneses of IPF and HF. Additionally, CCND1 and NAP1L3 were identified as potential diagnostic biomarkers for both HF and IPF. The results of our study contribute to the comprehension of the co-pathogenesis of HF and IPF at the genetic level and offer potential biological indicators for the early detection of both conditions.

Climate warming promotes collateral antibiotic resistance development in cyanobacteria.

Both cyanobacterial blooms and antibiotic resistance have aggravated worldwide and posed a great threat to public health in recent years. As a significant source and reservoir of water environmental resistome, cyanobacteria exhibit confusing discrepancy between their reduced susceptibility and their chronic exposure to antibiotic mixtures at sub-inhibitory concentrations. How the increasing temperature affects the adaptive evolution of cyanobacteria-associated antibiotic resistance in response to low-level antibiotic combinations under climate change remains unclear. Here we profiled the antibiotic interaction and collateral susceptibility networks among 33 commonly detected antibiotics in 600 cyanobacterial strains isolated from 50 sites across four eutrophicated lakes in China. Cyanobacteria-associated antibiotic resistance level was found positively correlated to antibiotic heterogeneity across all sites. Among 528 antibiotic combinations, antagonism was observed for 62 % interactions and highly conserved within cyanobacterial species. Collateral resistance was detected in 78.5 % of pairwise antibiotic interaction, leading to a widened or shifted upwards mutant selection window for increased opportunity of acquiring second-step mutations. We quantified the interactive promoting effect of collateral resistance and increasing temperature on the evolution of both phenotypic and genotypic cyanobacteria-associated resistance under chronic exposure to environmental level of antibiotic combinations. With temperature increasing from 16 °C to 36 °C, the evolvability index and genotypic resistance level increased by 1.25 - 2.5 folds and 3 - 295 folds in the collateral-resistance-informed lineages, respectively. Emergence of resistance mutation pioneered by tolerance, which was jointly driven by mutation rate and persister fraction, was found to be accelerated by increased temperature and antibiotic switching rate. Our findings provided mechanic insights into the boosting effect of climate warming on the emergence and development of cyanobacteria-associated resistance against collateral antibiotic phenotypes.

Gradually Self-Strengthen DNA Supramolecular Hydrogels.

The dynamic mechanical strength of the extracellular matrix (ECM) has been demonstrated to play important role in determining the cell behavior. Growing evidences suggest that the gradual stiffening process of the matrix is particularly decisive during tissue development and wound healing. Herein, a novel strategy to prepare hydrogels with gradually enhanced mechanical strength is provided. Such hydrogels could maintain the dynamic properties at their initial states, such as self-healing and shear-thinning properties. With subsequent slow covalent crosslinking, the stability and mechanical properties would be gradually improved. This method is useful for sequence programmability and oxidation strategies, which has provided an alternated tool to study cell behavior during dynamic increase in mechanical strength of ECM.

Fluorine-19 labeling of the tryptophan residues in the G protein-coupled receptor NK1R using the 5-fluoroindole precursor in Pichia pastoris expression.

In NMR spectroscopy of biomolecular systems, the use of fluorine-19 probes benefits from a clean background and high sensitivity. Therefore, 19F-labeling procedures are of wide-spread interest. Here, we use 5-fluoroindole as a precursor for cost-effective residue-specific introduction of 5-fluorotryptophan (5F-Trp) into G protein-coupled receptors (GPCRs) expressed in Pichia pastoris. The method was successfully implemented with the neurokinin 1 receptor (NK1R). The 19F-NMR spectra of 5F-Trp-labeled NK1R showed one well-separated high field-shifted resonance, which was assigned by mutational studies to the "toggle switch tryptophan". Residue-selective labeling thus enables site-specific investigations of this functionally important residue. The method described here is inexpensive, requires minimal genetic manipulation and can be expected to be applicable for yeast expression of GPCRs at large.

The Value of Nerve Ultrasound to Diagnose and Follow Up the Multifocal Neurolyphomatosis in the Upper Limb---- Case Report and Literature Review.

INTRODUCTION: Neurolymphomatosis (NL) is a rare disease. Ultrasound (US) plays a crucial role in diagnosing and following up the NL. CASE PRESENTATION: A 59-year-old man was hospitalized with acute pain in the left upper extremity. Ultrasound revealed segmental swelling of multiple nerves around his left elbow with abundant blood flow signals. Contrast-Enhanced Ultrasound (CEUS) showed a rapid, complete and homogenous enhancement in the nerve lesions in the early arterial phase. The NL was confirmed by imaging and flow cytometry, and he accepted chemotherapy. The posttherapeutic ultrasound showed that the nerves in the left upper limb were basically normal. Unfortunately, the patient died of cerebral metastasis in 5 months. CONCLUSION: The nerve US and CEUS can show specific manifestations and provide more diagnostic information about NL.

A tripartite evolutionary game study of low-carbon innovation system from the perspective of dynamic subsidies and taxes.

Traditional manufacturing industry is in the early stages of transition to low-carbon innovative production, and is in urgent need of a low-carbon innovation system to achieve the goal of carbon neutrality. In order to realize the effective supervision of enterprise carbon emissions, this paper constructs a tripartite evolutionary game model among the corporate, government and public from the perspective of dynamic subsidies and taxes. The main results are as follows. First, the increase in government subsidies to a certain extent will help encourage companies to choose low-carbon innovative production strategies, but more subsidies are not always better. Excessive subsidies will increase the cost of government regulation and reduce the probability of government regulation. Second, the tripartite evolutionary game system does not converge under the static subsidies and taxes mechanism. But the system could quickly converges to the stable condition under dynamic subsidies and taxes. The stable point is the situation of corporate low-carbon innovation, government regulation, and public supervision. Third, the public intervention and supervision can effectively prevent the phenomenon of government misconduct and enterprises over-emission production. And the influence of public reward and punishment is more effective for the government than for enterprises.

Reshaping the Landscape of the Genome: Toolkits for Precise DNA Methylation Manipulation and Beyond.

DNA methylation plays a pivotal role in various biological processes and is highly related to multiple diseases. The exact functions of DNA methylation are still puzzling due to its uneven distribution, dynamic conversion, and complex interactions with other substances. Current methods such as chemical- and enzyme-based sequencing techniques have enabled us to pinpoint DNA methylation at single-base resolution, which necessitated the manipulation of DNA methylation at comparable resolution to precisely illustrate the correlations and causal relationships between the functions of DNA methylation and its spatiotemporal patterns. Here a perspective on the past, recent process, and future of precise DNA methylation tools is provided. Specifically, genome-wide and site-specific manipulation of DNA methylation methods is discussed, with an emphasis on their principles, limitations, applications, and future developmental directions.

Impact of Helicobacter pylori colonization density and depth on gastritis severity.

BACKGROUND AND OBJECTIVES: Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis. METHODS: A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected. RESULTS: A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia. CONCLUSIONS: As the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.

Rational Design of DNA Hydrogels Based on Molecular Dynamics of Polymers.

In recent years, DNA has emerged as a fascinating building material to engineer hydrogel due to its excellent programmability, which has gained considerable attention in biomedical applications. Understanding the structure-property relationship and underlying molecular determinants of DNA hydrogel is essential to precisely tailor its macroscopic properties at molecular level. In this review, the rational design principles of DNA molecular networks based on molecular dynamics of polymers on the temporal scale, which can be engineered via the backbone rigidity and crosslinking kinetics, are highlighted. By elucidating the underlying molecular mechanisms and theories, it is aimed to provide a comprehensive overview of how the tunable DNA backbone rigidity and the crosslinking kinetics lead to desirable macroscopic properties of DNA hydrogels, including mechanical properties, diffusive permeability, swelling behaviors, and dynamic features. Furthermore, it is also discussed how the tunable macroscopic properties make DNA hydrogels promising candidates for biomedical applications, such as cell culture, tissue engineering, bio-sensing, and drug delivery.

The impact of climate change and human activities on the change in the net primary productivity of vegetation-taking Sichuan Province as an example.

Vegetation is an essential component of terrestrial ecosystems, influenced by climate change and human activities. Quantifying the relative contributions of climate change and human activities to vegetation dynamics is crucial for addressing global climate change. Sichuan Province is one of the essential ecological functional areas in the upper reaches of the Yangtze River, and its vegetation change is of great significance to the environmental function and ecological security of the Yangtze River Basin and southwest China. In this paper, the modified Carnegie-Ames-Stanford Approach(CASA) model was used to estimate the monthly NPP (Net Primary Productivity) of vegetation in Sichuan Province from 2000 to 2018, and the univariate linear regression analysis was used to analyze the temporal and spatial variation of vegetation NPP in Sichuan Province from 2000 to 2018. In addition, taking vegetation NPP as an index, Pearson correlation analysis, partial correlation analysis, and second-order partial correlation analysis were carried out to quantitatively analyze the contribution of climate change and human activities to vegetation NPP. Finally, the Hurst index and nonparametric Man-Kendall significance test were used to predict the future change trend of vegetation NPP in Sichuan Province. The results show that (1) from 2000 to 2018, the NPP of vegetation in Sichuan Province has a significant increasing trend (Slope = 6.09gC·m-2·a-1), with a multi-year average of 438.72 gC·m-2·a-1, showing a trend of low in the east and high in the middle. The response of vegetation NPP to altitude is different at different elevations; (2) the contribution rates of climate change and human activities to vegetation NPP change are 4.12gC·m-2·a-1 and 1.97gC·m-2·a-1, respectively. In contrast, the impact of human activities on NPP is more significant than climate change. Human activities are the main factors affecting vegetation restoration and degradation in Sichuan Province. However, the positive contribution to NPP change is less than climate change; (3) the future vegetation NPP change trend in Sichuan Province is mainly rising, and the same direction change trend is much larger than the reverse change trend. The areas with an increasing trend in the future account for 89.187% of the total area. This research helps understand the impact of climate change and human activities on vegetation change in Sichuan Province. It offers scientific bases for vegetation restoration and ecosystem management in Sichuan and the surrounding areas.

Identification and visualization of environmental microplastics by Raman imaging based on hyperspectral unmixing coupled machine learning.

Microplastics (MPs) are ubiquitous contaminants that have become an emerging pollutant of concern, potentially threatening human health and ecosystem environments. Although current detection methods can accurately identify various types of MPs, it remains necessary to develop non-destructive and rapid methods to meet growing demands for detection. Herein, we combine a hyperspectral unmixing method and machine learning to analyse Raman imaging data of environmental MPs. Five MPs types including poly(butylene adipate-co-terephthalate) (PBAT), poly(butylene succinate) (PBS), p-polyethylene (PE), polystyrene (PS) and polypropylene (PP) were visualized and identified. Individual or mixed pure or aged MPs along with environmental samples were analysed by Raman imaging. Alternating volume maximization (AVmax) combined with unconstrained least squares (UCLS) method estimated end members and abundance maps of each of the MPs in the samples. Pearson correlation coefficients (r) were used as the evaluation index; the results showed that there is a high similarity between the raw spectra and the average spectra calculated by AVmax. This indicates that Raman imaging based on machine learning and hyperspectral unmixing is a novel imaging analysis method that can directly identify and visualize MPs in the environment.

Clinical neuromodulatory effects of deep brain stimulation in disorder of consciousness: A literature review.

BACKGROUND: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions. OBJECTIVE: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients. METHODS: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science). RESULTS: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian-parafascicular complex (CM-pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 µs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow-up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates. CONCLUSION: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population.

Dissecting the intricacies of human antibody responses to SARS-CoV-1 and SARS-CoV-2 infection.

The 2003 severe acute respiratory syndrome coronavirus (SARS-CoV-1) causes more severe disease than SARS-CoV-2, which is responsible for COVID-19. However, our understanding of antibody response to SARS-CoV-1 infection remains incomplete. Herein, we studied the antibody responses in 25 SARS-CoV-1 convalescent patients. Plasma neutralization was higher and lasted longer in SARS-CoV-1 patients than in severe SARS-CoV-2 patients. Among 77 monoclonal antibodies (mAbs) isolated, 60 targeted the receptor-binding domain (RBD) and formed 7 groups (RBD-1 to RBD-7) based on their distinct binding and structural profiles. Notably, RBD-7 antibodies bound to a unique RBD region interfaced with the N-terminal domain of the neighboring protomer (NTD proximal) and were more prevalent in SARS-CoV-1 patients. Broadly neutralizing antibodies for SARS-CoV-1, SARS-CoV-2, and bat and pangolin coronaviruses were also identified. These results provide further insights into the antibody response to SARS-CoV-1 and inform the design of more effective strategies against diverse human and animal coronaviruses.

Helicobacter pylori infection reduces the efficacy of cancer immunotherapy: A systematic review and meta-analysis.

BACKGROUND: Cancer immunotherapy has shown promising results in several tumors, but its efficacy is influenced by the immune state of the body. Helicobacter pylori (H. pylori) infection can modulate the immune function of the body through various pathways, ultimately affecting the effectiveness of cancer immunotherapy. AIM: In this meta-analysis, we aimed to explore the association between H. pylori infection and the efficacy of cancer immunotherapy. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant articles. We extracted and pooled the hazard ratio (HR) of the overall survival (OS) and progression-free survival (PFS) by Review Manager 5.4. RESULTS: Our analysis included four studies with a total of 263 participants. Compared to the control group, patients receiving cancer immunotherapy with H. pylori infection had a shorter OS (HR = 2.68, 95% CI: 2.00-4.11, p < 0.00001) and PFS (HR = 2.25, 95% CI: 1.66-3.60, p < 0.00001). CONCLUSION: Our meta-analysis suggested that H. pylori infection has a detrimental effect on cancer immunotherapy.

Epileptic Seizure Prediction Using Attention Augmented Convolutional Network.

Early seizure prediction is crucial for epilepsy patients to reduce accidental injuries and improve their quality of life. Identifying pre-ictal EEG from the inter-ictal state is particularly challenging due to their nonictal nature and remarkable similarities. In this study, a novel epileptic seizure prediction method is proposed based on multi-head attention (MHA) augmented convolutional neural network (CNN) to address the issue of CNN's limit of capturing global information of input signals. First, data enhancement is performed on original EEG recordings to balance the pre-ictal and inter-ictal EEG data, and the EEG recordings are sliced into 6-second-long EEG segments. Subsequently, EEG time-frequency distribution is obtained using Stockwell transform (ST), and the attention augmented convolutional network is employed for feature extraction and classification. Finally, post-processing is utilized to reduce the false prediction rate (FPR). The CHB-MIT EEG database was used to evaluate the system. The validation results showed a segment-based sensitivity of 98.24% and an event-based sensitivity of 94.78% with a FPR of 0.05/h were yielded, respectively. The satisfying results of the proposed method demonstrate its possible potential for clinical applications.

A novel magnetic Fe3O4/cellulose nanofiber/polyethyleneimine/thiol-modified montmorillonite aerogel for efficient removal of heavy metal ions: Adsorption behavior and mechanism study.

To efficiently remove heavy metals from wastewater, designing an adsorbent with high adsorption capacity and ease of recovery is necessary. This paper presents a novel magnetic hybridized aerogel, Fe3O4/cellulose nanofiber/polyethyleneimine/thiol-modified montmorillonite (Fe3O4/CNF/PEI/SHMMT), and explores its adsorption performance and mechanism for Pb2+, Cu2+, and Cd2+ in aqueous solutions. The hybrid aerogel has a slit-like porous structure and numerous exposed active sites, which facilitates the uptake of metal ions by adsorption. Pb2+, Cu2+, and Cd2+ adsorption by the hybridized aerogel followed the second-order kinetics and the Langmuir isotherm model, the maximum adsorption of Pb2+, Cu2+, and Cd2+ at 25 °C, pH = 6, 800 mg/L was 429.18, 381.68 and 299.40 mg/g, respectively. The adsorption process was primarily attributed to monolayer chemical adsorption, a spontaneous heat-absorption reaction. FTIR, XPS and DFT studies confirmed that the adsorption mechanisms of Fe3O4/CNF/PEI/SHMMT on Pb2+, Cu2+, and Cd2+ were mainly chelation, coordination, and ion exchange. The lowest adsorption energy of Pb2+ on the hybrid aerogel was calculated to be -2.37 Ha by DFT, which indicates that the sample has higher adsorption affinity and preferential selectivity for Pb2+. After 5 cycles, the adsorption efficiency of the aerogel was still >85 %. The incorporation of Fe3O4 improved the mechanical properties of the aerogel. The Fe3O4/CNF/PEI/SHMMT has fast magnetic responsiveness, and it is easy to be separated and recovered after adsorption, which is a promising potential for the treatment of heavy metal ions.

Structural insights into MIC2 recognition by MIC2-associated protein in Toxoplasma gondii.

Microneme protein 2 (MIC2) and MIC2-associated protein (M2AP) play crucial roles in the gliding motility and host cell invasion of Toxoplasma gondii. Complex formation between MIC2 and M2AP is required for maturation and transport from the microneme to the parasite surface. Previous studies showed that M2AP associates with the 6th TSR domain of MIC2 (TSR6), but the detailed interaction remains unclear. In this study, we report crystal structures of M2AP alone and in complex with TSR6. TSR domains have an unusually thin, long structure with a layer of intercalated residues on one side. The non-layered side of TSR6 with hotspot residue His-620 at the center binds to M2AP. Remarkably, we show that TSR6 residue Y602 is dynamic; it equilibrates between being part of the layer (the layered state) and in a flipped-out state in the absence of M2AP. However, when bound to M2AP, Y602 shifts to the flipped-out state. Our findings provide insights into the association and stabilization of MIC2-M2AP complex, and may be used to develop new therapies to prevent infections caused by this parasite.

Two-Dimensional NMR Spectroscopy of the G Protein-Coupled Receptor A2AAR in Lipid Nanodiscs.

Eight hundred and twenty-six human G protein-coupled receptors (GPCRs) mediate the actions of two-thirds of the human hormones and neurotransmitters and over one-third of clinically used drugs. Studying the structure and dynamics of human GPCRs in lipid bilayer environments resembling the native cell membrane milieu is of great interest as a basis for understanding structure-function relationships and thus benefits continued drug development. Here, we incorporate the human A2A adenosine receptor (A2AAR) into lipid nanodiscs, which represent a detergent-free environment for structural studies using nuclear magnetic resonance (NMR) in solution. The [15N,1H]-TROSY correlation spectra confirmed that the complex of [u-15N, ~70% 2H]-A2AAR with an inverse agonist adopts its global fold in lipid nanodiscs in solution at physiological temperature. The global assessment led to two observations of practical interest. First, A2AAR in nanodiscs can be stored for at least one month at 4 °C in an aqueous solvent. Second, LMNG/CHS micelles are a very close mimic of the environment of A2AAR in nanodiscs. The NMR signal of five individually assigned tryptophan indole 15N-1H moieties located in different regions of the receptor structure further enabled a detailed assessment of the impact of nanodiscs and LMNG/CHS micelles on the local structure and dynamics of A2AAR. As expected, the largest effects were observed near the lipid-water interface along the intra- and extracellular surfaces, indicating possible roles of tryptophan side chains in stabilizing GPCRs in lipid bilayer membranes.

Impact of different industrial activities on heavy metals in floodplain soil and ecological risk assessment based on bioavailability: A case study from the Middle Yellow River Basin, northern China.

Understanding the impact of different industrial activities on heavy metals and conducting scientific ecological risk assessments are critical to the management of heavy metal pollution. The present study compared soils affected by different industrial activities in three types of industrial cities (coal city, oil-gas city, and economic city) to control samples and examined the ecological risk based on bioavailability in the Middle Yellow River Basin. The findings revealed that the impact characteristics of different industrial activities on soil heavy metals in the research area were different. Both coal-based and oil-gas industry activities had a minor impact on soil heavy metals, whereas economic industry activities in the southern part had a major impact, as evidenced by significant enrichment of Cd, Hg, Cu, Pb, and Zn. In principal component analysis, the soil heavy metals affected by economic industry activities designated a distinct source from the control samples, particularly the anthropogenic sources represented by Hg and Cd. In the context of heavy metals in chemical form, three types of industrial activities all had an effect on bioavailability (0.72-24.27%) and could increase migratory activity in the environment. Furthermore, both traditional and improved assessments, based on total content and bioavailability, showed a low ecological risk near coal cities and oil-gas cities in the middle and northern parts, while there was a medium-high ecological risk near economically developed cities in the south, particularly Tianshui, Baoji, Qishan, Xianyang, Xi'an, and Tongchuan. In comparison, improved risk assessment based on bioavailability tends to not only compensate for an overestimation in traditional risk assessment from the perspective of total content, but additionally achieve a more reasonable, effective, and advanced assessment of heavy metal risks in scientific research. The outcome of this study has significance for the ecological conservation and high-quality development of the Yellow River Basin.

Selective polypeptide ligand binding to the extracellular surface of the transmembrane domains of the class B GPCRs GLP-1R and GCGR.

Crystal and cryo-EM structures of the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) bound with their peptide ligands have been obtained with full-length constructs, indicating that the extracellular domain (ECD) is indispensable for specific ligand binding. This article complements these data with studies of ligand recognition of the two receptors in solution. Paramagnetic NMR relaxation enhancement measurements using dual labeling with fluorine-19 probes on the receptor and nitroxide spin labels on the peptide ligands provided new insights. The glucagon-like peptide-1 (GLP-1) was found to interact with GLP-1R by selective binding to the extracellular surface. The ligand selectivity toward the extracellular surface of the receptor was preserved in the transmembrane domain (TMD) devoid of the ECD. The dual labeling approach further provided evidence of cross-reactivity of GLP-1R and GCGR with glucagon and GLP-1, respectively, which is of interest in the context of medical treatments using combinations of the two polypeptides.