The first prospective application of AIGS real-time fluorescence PCR in precise diagnosis and treatment of meningioma: Case report

BackgroundThe emergence of the new WHO classification standard in 2021 incorporated molecular characteristics into the diagnosis system for meningiomas, making the diagnosis and treatment of meningiomas enter the molecular era.Recent findingsAt present, there are still some problems in the clinical molecular detection of meningioma, such as low attention, excessive detection, and a long cycle. In order to solve these clinical problems, we realized the intraoperative molecular diagnosis of meningioma by combining real-time fluorescence PCR and AIGS, which is also the first known product applied to the intraoperative molecular diagnosis of meningioma.Implications for practiceWe applied AIGS to detect and track a patient with TERTp mutant meningioma, summarized the process of intraoperative molecular diagnosis, and expounded the significance of intraoperative molecular diagnosis under the new classification standard, hoping to optimize the clinical decision-making of meningioma through the diagnosis and treatment plan of this case

Molecular basis of ligand recognition and activation of human V2 vasopressin receptor.

Vasopressin type 2 receptor (V2R) belongs to the vasopressin (VP)/oxytocin (OT) receptor subfamily of G protein-coupled receptors (GPCRs), which comprises at least four closely related receptor subtypes: V1aR, V1bR, V2R, and OTR. These receptors are activated by arginine vasopressin (AVP) and OT, two endogenous nine-amino acid neurohypophysial hormones, which are thought to mediate a biologically conserved role in social behavior and sexual reproduction. V2R is mainly expressed in the renal collecting duct principal cells and mediates the antidiuretic action of AVP by accelerating water reabsorption, thereby playing a vital role in controlling water homeostasis. Moreover, numerous gain-of-function and loss-of-function mutations of V2R have been identified and are closely associated with human diseases, including nephrogenic syndrome of inappropriate diuresis (NSIAD) and X-linked congenital nephrogenic diabetes insipidus (NDI). Thus, V2R has attracted intense interest as a drug target. However, due to a lack of structural information, how AVP recognizes and activates V2R remains elusive, which hampers the V2R-targeted drug design. Here, we determined a 2.6 Å resolution cryo-EM structure of the full-length, G s -coupled human V2R bound to AVP (Fig. 1a; Supplementary information, Table S1). The G s protein was engineered based on mini-G s that was used in the crystal structure determination of the G s -coupled adenosine A 2A receptor (A 2A R) to stabilize the V2R–G s protein complex (Supplementary information, Data S1). The final structure of the AVP–V2R–G s complex contains all residues of AVP (residues 1–9), the Gα s Ras-like domain, Gβγ subunits, Nb35, scFv16, and the V2R residues from T31 to L339 8.57 (superscripts refer to Ballesteros–Weinstein numbering). The majority of amino acid side chains, including AVP, transmembrane domain (TMD), all flexible intracellular loops (ICLs) and extracellular loops (ECLs) except for ICL3 and G185–G188 in ECL2, were well resolved in the model, refined against the EM density map (Fig. 1a; Supplementary information, Figs. S1–3). The complex structure can provide detailed information on the binding interface between AVP and helix bundle of the receptor, as well as the receptor–G s interface

A new method for the characterization of microcracks based on seepage characteristics

Microcracks are the main seepage channels and reservoir space for oil and gas in dense sandstone reservoirs, and the degree of development dominates the reservoir’s high and stable production capacity. A new method has been devised to address the lack of quantitative identification and characterization methods for microcrack networks. The method is based on core stress sensitivity, permeability anisotropy, and two-phase seepage rule testing. By improving upon the traditional black oil model, this method can accurately calculate the impact that microcracks of varying degrees of development have on the capacity of tight oil reservoirs. The study shows that 1) the higher the degree of microcrack development, the stronger the reservoir stress sensitivity and the greater the permeability anisotropy. As the degree of microcrack development increases, the irreducible water saturation decreases, the residual oil saturation gradually increases, and the oil–water two-phase co-infiltration zone becomes more extensive and smaller. The degree of microcrack development in tight reservoirs can be characterized based on the seepage characteristic parameters; 2) a microcrack characterization method and classification criteria have been established. It is based on stress sensitivity coefficients, permeability anisotropy parameters, and phase seepage characteristics in cores with different microcrack development degrees. For the first time, the method enables a macroscopic-level description of microcrack seepage; 3) numerical calculations show that the degree of microcrack development significantly affects the reservoir’s oil production and water production. The higher the degree of microcrack development, the higher the reservoir’s initial oil production and cumulative oil production. However, when the degree of microcrack development is too high, the microcracks are connected, thus exhibiting the nature of large fractures. This strengthens the bypassing communication effect and causes the microscopic inhomogeneity to strengthen, the oil production decreases rapidly, and water production increases quickly at the later stage. This research result enriches the reservoir microcrack characterization and evaluation system, which has essential theoretical guidance and practical significance for the rational and effective development of tight oil and tight sandstone gas

Bidirectional Role of β2-Adrenergic Receptor in Autoimmune Diseases

Disorder of the sympathetic nervous system (SNS) is closely related to the pathogenesis of various autoimmune diseases (ADs). Catecholamine triggered beta2-adrenergic receptor (β2-AR) signaling is important in creating a bidirectional response in the progression of ADs due to factors including diverse expression patterns, single nucleotide polymorphisms (SNPs), biased signals, and desensitization of β2-AR, as well as different subtypes of Gα binding to β2-AR. In this review, we summarize the actions of β2-AR signaling in regulating the functions of immunocytes and in the pathogenesis of ADs, and the application of β2-AR agonists or antagonists in treating major types of ADs is also discussed. We suggest that restoring the immune balance via a soft regulation of the expression or activation of β2-AR is one of the promising therapeutic strategies for systematic ADs

Strategies in activating lymphatic system on symptom distress and health-related quality of life in patients with heart failure: secondary analysis of a pilot randomized controlled trial

BackgroundAbnormal interstitial fluid accumulation remains the major cause for patients with heart failure (HF) to endure a myriad of distressing symptoms and a decline in their health-related quality of life (HRQoL). The lymphatic system is essential in regulating fluid balance within the interstitial compartment and has recently been recognized as an important target for the prevention and mitigation of congestion. This study aimed to investigate the effects of exercises in activating lymphatic system on symptom distress and HRQoL among patients with HF.Methods and resultsThis was a pre-determined, secondary analysis of the TOLF-HF [The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF)] study, a two-arm pilot randomized controlled trial evaluating the preliminary effects of the lymphatic exercise intervention in enhancing interstitial decongestion among patients with HF. Participants were randomized to receive either a four-week TOLF-HF program in addition to standard care or standard care alone. The Chinese version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was employed to measure symptom distress and HRQoL before and after the intervention. Data analyses included descriptive statistics, the independent sample t-test, Pearson’s chi-square test, the Mann-Whitney U test, and covariance analysis. Of the 66 patients enrolled, 60 completed the study. The study results exhibited that the TOLF-HF intervention were effective in alleviating both physical and psychological symptom distress. The intervention group yielded significantly lower MLHFQ total scores in comparison to the control group. The odd ratio of achieving meaningful improvement in HRQoL in TOLF-HF group was 2.157 times higher than those in the control group.ConclusionsThe TOLF-HF program focusing on activating lymphatic system was effective in alleviating physical and psychological symptom distress as well as improving HRQoL for patients with HF. The tolerability, feasibility, and effectiveness of the TOLF-HF intervention make it a promising intervention for patients to manage HF.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier (ChiCTR2000039121)

Chlorpyrifos And Chlorpyrifos-methyl Can Promote Conjugative Transfer of Antibiotic Resistance Genes

Antibiotic misuse induces the production of antibiotic resistance genes (ARGs), leading to the global spread of antimicrobial resistance (AMR), which poses a major threat to human health. Conjugative transfer, as the main process of ARGs propagation, is sensitively influenced by coexisting contaminants. Chlorpyrifos and chlorpyrifos-methyl, as organophosphorus insecticides widely used in agriculture, have been shown to induce cytotoxicity such as elevated levels of reactive oxygen radicals (ROS) and lipid peroxidation. This is similar to the mechanism by which antibiotics promote the conjugative transfer of ARGs, based on which we hypothesized that chlorpyrifos and chlorpyrifos-methyl could promote conjugative transfer. However, the effect of chlorpyrifos and chlorpyrifos-methyl on conjugative transfer is unclear. Therefore, we constructed RP4 plasmid-mediated conjugation system and confirmed that chlorpyrifos and chlorpyrifos-methyl can promote conjugative transfer by inducing oxidative stress in donor and recipient bacteria. Our research reveals the risk of ARM spread in organophosphorus insecticides and ARGs co-contaminated environments

Chlorpyrifos And Chlorpyrifos-methyl Can Promote Conjugative Transfer of Antibiotic Resistance Genes

Antibiotic misuse induces the production of antibiotic resistance genes (ARGs), leading to the global spread of antimicrobial resistance (AMR), which poses a major threat to human health. Conjugative transfer, as the main process of ARGs propagation, is sensitively influenced by coexisting contaminants. Chlorpyrifos and chlorpyrifos-methyl, as organophosphorus insecticides widely used in agriculture, have been shown to induce cytotoxicity such as elevated levels of reactive oxygen radicals (ROS) and lipid peroxidation. This is similar to the mechanism by which antibiotics promote the conjugative transfer of ARGs, based on which we hypothesized that chlorpyrifos and chlorpyrifos-methyl could promote conjugative transfer. However, the effect of chlorpyrifos and chlorpyrifos-methyl on conjugative transfer is unclear. Therefore, we constructed RP4 plasmid-mediated conjugation system and confirmed that chlorpyrifos and chlorpyrifos-methyl can promote conjugative transfer by inducing oxidative stress in donor and recipient bacteria. Our research reveals the risk of ARM spread in organophosphorus insecticides and ARGs co-contaminated environments

Landscape Patterns Affect Precipitation Differing across Sub-climatic Regions

Assessment of the impacts of landscape patterns on regional precipitation will help improve ecosystem management and strategies for adaption to global changes. This study aimed to identify the key landscape metrics that affect precipitation across three sub-climatic regions in Inner Mongolia, China, using 266 landscape metrics and daily precipitation data from 38 weather stations for 1995, 2000, 2005, and 2015. Pearson correlation, stepwise linear regression, and Redundancy analysis were used to identify the contributions of landscape patterns to local precipitation in each sub-climatic region. Three-year datasets were used for model development and a one-year data set was used for validation. It was found that the contribution of landscape patterns is higher than that of climatic variations in semi-arid or humid regions. The Core Area Coefficient of Variance (CACoV) of grasslands and Landscape Area (TLA) in non-irrigated croplands have a negative relationship with precipitation in arid regions. Further, the Total Core Area Index (TCAI) of grasslands has a negative correlation with precipitation, while the area proportion (C%LAND) in waters has a significant positive relationship with precipitation in semi-arid regions. Additionally, the Mean Core Area (MCA), Core Area (CA), and Core Area Standard Deviation (CASD) of grasslands and Total Core Area Index (TCAI) of waters are negatively related to precipitation in humid regions. Suitable land use configuration and composition, especially the proportion of grasslands and waters, should be considered in ecosystem management for alleviating the possible harmful effects due to climate change

Molecular Mechanisms of T Cells Activation by Dendritic Cells in Autoimmune Diseases

The interaction between T cell and dendritic cells (DCs) that leads to T cell activation affects the progression of the immune response including autoimmune diseases. Antigen presentation on immune cell surface, formation of an immunological synapse (IS), and specific identification of complex by T cells including two activating signals are necessary steps that lead to T cell activation. The formation of stimulatory IS involves the inclusion of costimulatory molecules, such as ICAM-1/LFA-1 and CD28/B7-1, and so on. Some fusion proteins and monoclonal antibodies targeting costimulatory molecules have been developed and approved to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (T1D), inflammatory bowel disease (IBD), and psoriasis. These biological agents, including CTLA-4- and LFA-3-Ig, anti-CD3 monoclonal antibody, could prevent the successful engagement of DCs by T cell with significant efficacy and safety profile. In this article, we reviewed the molecular mechanisms of T cell activation during the interaction between T cells and DCs, and summarized some biological agents that target costimulatory molecules involved in the regulation of T cell activation