Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the efficacy of evolocumab remain unclear. This study aimed to investigate sex differences in the efficacy of evolocumab using real-world data.
View Article and Find Full Text PDFThe tumor microenvironment (TME), especially with its complicated metabolic characteristics, will dynamically affect the proliferation, migration, and drug response of tumor cells. Rapid metabolic analysis brings out a deeper understanding of the TME, while the susceptibility and environmental dependence of metabolites extremely hinder real-time metabolic profiling since the TME is easily disrupted. Here, we directly integrated paper spray ionization mass spectrometry with a paper-based three-dimensional (3D) tumor model, realizing the rapid capture of metabolic gradients.
View Article and Find Full Text PDFIntroduction: Neoadjuvant immunotherapy plus chemotherapy has ushered in a new era for surgical treatment for patients with NSCLC. This study aimed to examine the efficacy and safety of neoadjuvant immunotherapy plus chemotherapy in NSCLC.
Methods: Eligible studies were identified from PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.
Type 1 innate lymphoid cells (ILC1s) are a class of tissue-resident cells with antitumor activity, suggesting its possible role in solid tumor immune surveillance, but it is not clear whether manipulating ILC1s can induce potent antitumor immune responses. Here, we found that G-protein-coupled receptor 34 (GPR34), a receptor for lysophosphatidylserine (LysoPS), was highly expressed on ILC1s but not on conventional natural killer cells in the tumor microenvironment. LysoPS was enriched in the tumor microenvironment and could inhibit ILC1 activation via GPR34.
View Article and Find Full Text PDFThis study explores the mechanism by which obstructive jaundice (OJ) induces liver damage through pyroptosis. We induced OJ in rats via bile duct ligation and assessed liver damage using serum biochemical markers and histological analysis of liver tissue. Pyroptosis was investigated through immunofluorescence, ELISA, Western blot, and quantitative RT-PCR techniques.
View Article and Find Full Text PDFBackground: Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers.
View Article and Find Full Text PDFDeep learning (DL) has substantially enhanced natural language processing (NLP) in healthcare research. However, the increasing complexity of DL-based NLP necessitates transparent model interpretability, or at least explainability, for reliable decision-making. This work presents a thorough scoping review of explainable and interpretable DL in healthcare NLP.
View Article and Find Full Text PDFTo investigate the regularity and characteristics of adverse drug reaction (ADR) of reactive cutaneous capillary endothelial proliferation caused by Camrelizumab, so as to provide reference for clinical rational use of drugs. Searching for case reports of Camrelizumab-induced reactive cutaneous capillary endothelial proliferation (RCCEP) in databases such as China Biology Medicine disc, VIP Database, CNKI, Wanfang Medical, PubMed, Wiley online library, Embase with "Carritzumab/Ericab," "SHR-1210," "Reactive cutaneous capillary endothelial proliferation," "Reactive capillary hemangiomas," and "Capillary proliferation" as search terms. The retrieval time is from the establishment of the database to February 2022.
View Article and Find Full Text PDFBackground: Gallbladder cancer (GC) is a uncommon and highly malignant tumor. This study compared the effects of simple cholecystectomy (SC) and extended cholecystectomy (EC) on the long-term survival of stage I GC.
Methods: Patients with stage I GC between 2004 and 2015 in the SEER database were selected.
The mechanisms whereby protein ions are released from nanodroplets at the liquid-gas interface have continued to be controversial since electrospray ionization (ESI) mass spectrometry was widely applied in biomolecular structure analysis in solution. Several viable pathways have been proposed and verified for single-domain proteins. However, the ESI mechanism of multi-domain proteins with more complicated and flexible structures remains unclear.
View Article and Find Full Text PDFThe highly variable response rates to immunotherapies underscore our limited knowledge about how tumors can manipulate immune cells. Here the membrane topology of natural killer (NK) cells from patients with liver cancer showed that intratumoral NK cells have fewer membrane protrusions compared with liver NK cells outside tumors and with peripheral NK cells. Dysregulation of these protrusions prevented intratumoral NK cells from recognizing tumor cells, from forming lytic immunological synapses and from killing tumor cells.
View Article and Find Full Text PDFWalnut () is an important nut tree species in the world, whereas walnut trees often face inadequate phosphorus (P) levels of soil, negatively limiting its growth and yield. Arbuscular mycorrhizal fungi (AMF) can colonize walnut roots, but whether and how AMF promotes walnut growth, physiological activities, and P acquisition is unclear. The present study aimed to evaluate the effects of on plant growth, chlorophyll component concentrations, leaf gas exchange, sugar and P concentrations, and expression of () and () genes in leaves of .
View Article and Find Full Text PDFMore than 50 mutations in the gene result in heterogeneous forms of frontotemporal lobar dementia with tau inclusions (FTLD-Tau). However, early pathogenic events that lead to disease and the degree to which they are common across mutations remain poorly understood. The goal of this study is to determine whether there is a common molecular signature of FTLD-Tau.
View Article and Find Full Text PDFDirect observation of metabolites in living cells by mass spectrometry offers a bright future for biological studies but also suffers a severe challenge to untargeted peak assignment to tentative metabolite candidates. In this study, we developed a method combining stable isotope tracing and induced electrospray mass spectrometry for living-cells metabolite measurement and identification. By using C-glucose and ammonium chloride-N as the sole carbon and nitrogen sources for cell culture, Escherichia coli synthesized metabolites with N and C elements.
View Article and Find Full Text PDFAims: To investigate the potential inhibitory effect of Hydroxysafflor yellow A (HSYA) on myocardial fibrosis induced by isoproterenol (ISO) and angiotensin II (Ang II) and the possible underlying mechanism.
Methods: Mice were injected subcutaneously with ISO and given HSYA by gavage in vivo. Masson's trichrome staining, immunohistochemical staining and immunofluorescence assays were conducted to evaluate the expression and localization of collagen and inflammatory cytokines, respectively.
Aspergillus fumigatus is an important opportunistic fungal pathogen and causes invasive pulmonary aspergillosis in conditions with compromised innate antifungal immunity, including chronic granulomatous disease, which results from inherited deficiency of the superoxide-generating leukocyte NADPH oxidase 2 (NOX2). Derivative oxidants have both antimicrobial and immunoregulatory activity and, in the context of A. fumigatus, contribute to both fungal killing and dampening inflammation induced by fungal cell walls.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2023
Native mass spectrometry, which takes a high concentration of ammonium acetate (NHOAc) for ionization, coupled with tedious and solvent-consuming purification, which separates proteins from complicated environments, has shown great potential for proteins and their complexes. A high level of nonvolatile salts in the endogenous intracellular environment results in serious ion suppression and has been one of the bottlenecks for native mass spectrometry, especially for protein complexes. Herein, an integrated protocol utilizing the inner surface of a micropipette for rapid purification, desorption, and ionization of peptide-metal interaction at subfemtomole level in cell lysate was demonstrated for native mass spectrometry.
View Article and Find Full Text PDFRapid monitoring of real bacterial metabolic perturbations to antibiotics may be helpful to better understand the mechanisms of action and more targeted treatment. In this study, the real metabolic responses to antibiotic treatment in living bacteria were profiled rapidly by induced electrospray ionization mass spectrometry. Significant metabolic perturbations were profiled after antibiotic treatment compared with untreated bacteria.
View Article and Find Full Text PDFThe leukocyte NADPH oxidase 2 (NOX2) regulates inflammation independent of its antimicrobial activity. Inherited defects in NOX2 lead to chronic granulomatous disease (CGD), associated with recurrent bacterial and fungal infections, often with excessive neutrophilic inflammation that results in significant inflammatory burden and tissue damage. We previously showed that excessive leukotriene B4 (LTB4) production by NOX2-deficient mouse neutrophils was a key driver of elevated lung neutrophil infiltration in the initial response to pulmonary challenge with the model fungal particle zymosan.
View Article and Find Full Text PDFThe leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation. Genetic defects in NOX2 result in chronic granulomatous disease (CGD), associated with microbial infections and inflammatory disorders, often involving the lung. Alveolar macrophages (AMs) are the predominant immune cell in the airways at steady state, and limiting their activation is important, given the constant exposure to inhaled materials, yet the importance of NOX2 in this process is not well understood.
View Article and Find Full Text PDF