NLRP3 inflammasome activation and macrophage distribution in kidney tissues from patients with acute oxalate nephropathy.

Background: The current study was initiated to evaluate renal nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway activation and macrophage subtype distribution and their clinicopathological significance in a cohort of oxalate-induced acute kidney injury. Methods: Twelve patients with biopsy-proven acute oxalate nephropathy (AON) from January 2016 to October 2022 were retrospectively enrolled, with estimated glomerular filtration rate (eGFR)-matched 24 patients with acute tubulointerstitial nephritis (ATIN) as disease control. Pathological lesions as well as markers of NLRP3 inflammasome pathway and macrophage phenotype detected by immunohistochemistry staining were semi-quantitatively analyzed. Results: Oxalate depositions were found in 5% to 20% of tubules with a positive correlation with Sirius Red staining in AON specimens (rp = 0.668, p = 0.02). Disruption of tubular basement membrane and inflammatory cell reaction was more prominent in specimens of AON (both p < 0.05) as compared with ATIN specimens. The expressions of NLRP3, caspase-1, and gasdermin D were significantly increased in AON specimens as well (all p < 0.05). Patients with M1/M2 macrophage ratio <1 were found with more chronic tubulointerstitial lesions and presented with lower eGFR at the last follow-up (24.8  10.6 mL/min/1.73 m2 vs. 55.1  21.2 mL/min/1.73 m2, p = 0.02) in the AON group. Conclusion: The NLRP3 inflammasome pathway was activated in the kidneys of AON patients, and the ratio of M1 and M2 macrophages was associated with chronicity of pathological changes, which needs further exploration.

Nphos: Database and Predictor of Protein N-phosphorylation.

Protein N-phosphorylation is widely present in nature and participates in various biological processes. However, current knowledge on N-phosphorylation is extremely limited compared to that on O-phosphorylation. In this study, we collected 11,710 experimentally verified N-phosphosites of 7344 proteins from 39 species and subsequently constructed the database Nphos to share up-to-date information on protein N-phosphorylation. Upon these substantial data, we characterized the sequential and structural features of protein N-phosphorylation. Moreover, after comparing hundreds of learning models, we chose and optimized gradient boosting decision tree (GBDT) models to predict three types of human N-phosphorylation, achieving mean area under the receiver operating characteristic curve (AUC) values of 90.56%, 91.24%, and 92.01% for pHis, pLys, and pArg, respectively. Meanwhile, we discovered 488,825 distinct N-phosphosites in the human proteome. The models were also deployed in Nphos for interactive N-phosphosite prediction. In summary, this work provides new insights and points for both flexible and focused investigations of N-phosphorylation. It will also facilitate a deeper and more systematic understanding of protein N-phosphorylation modification by providing a data and technical foundation. Nphos is freely available at http://www.bio-add.org/Nphos/ and http://ppodd.org.cn/Nphos/.

Critical Role of S100A9 in Sepsis-associated Acute Kidney Injury: Mechanistic Insights through Pyroptosis Pathway Modulation.

This study investigates the role of S100A9 in sepsis-associated AKI (SA-AKI) through the lens of pyroptosis, a controlled form of cell death mediated by the gasdermin protein family. Using C57BL/6 mice and S100A9 knockout mice subjected to cecal ligation and puncture (CLP), RNA sequencing and bioinformatics analyses revealed differentially expressed genes (DEGs) related to inflammation and immune responses, with notable upregulation of S100A9. Functional enrichment analyses (GO and KEGG) indicated these DEGs are involved in interferon-beta response, immune processes, and cell adhesion. Protein-protein interaction (PPI) network analyses further emphasized S100A9's pivotal role in SA-AKI.Clinical validation measured S100A9 levels in serum and urine samples from SA-AKI patients and healthy volunteers, finding elevated S100A9 levels in the former. In vivo experiments showed that S100A9 knockout mice exhibited reduced kidney injury and inflammation, indicated by lower serum creatinine, urea nitrogen, and inflammatory markers (IL-1ß and IL-18). Histopathological analyses and immunohistochemistry confirmed less renal damage and reduced expression of cleaved IL-1ß and GSDMD-N in S100A9-deficient mice. Electron microscopy and Western blotting validated that S100A9 deficiency mitigates caspase-1-dependent pyroptosis.Cellular experiments with HK-2 cells demonstrated that S100A9 knockdown alleviated LPS-induced cell damage and reduced pyroptosis markers. These findings illuminate S100A9's involvement in NLRP3 inflammasome activation and pyroptosis, suggesting potential therapeutic targets for SA-AKI. Targeting S100A9 may offer new therapeutic avenues, improving outcomes for sepsis-related kidney injury patients. Future research should aim to validate these findings in larger clinical settings.

Regulating oxygen vacancies in ammonium vanadate electrode materials for advanced aqueous zinc ion batteries.

In the past decade, vanadates have attracted one's attention as the electrode materials for aqueous zinc ion batteries (AZIBs). Nevertheless, their structural instability and sluggish ion/electron dynamics lead to an inevitable decline in the electrochemical performance. To address these issues, we introduce oxygen vacancies into NH4V4O10 nanosheets to improve the ion transport rate during the electrochemical reaction. The prepared NHVO-40 samples provide many active sites compared to NH4V4O10 materials. The assembled cell delivers a capacity of 452.03 mAh g-1 at a current density of 0.2 A g-1. It also presents a retention rate of 94.6% at 10 A g-1 after 4000 times cycling. In addition, they still possess an energy density of 332.5 Wh kg-1 at a power density of 70 W kg-1.

Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements. We generated a series of mutants and screened them in vitro to assess their potential for forming a stable pre-F. In animals, the immunogenicity of a representative mutant F protein, with a conformation confirmed by cryo-electron microscopy, elicited levels of neutralizing antibodies and protection against RSV-induced lung damage that were comparable to those of DS-Cav1, a pre-F used in a licensed vaccine.

Microencapsulation of total saponins from stem and leaf of Panax notoginseng by freeze and spray drying: Process optimization, physicochemical properties, structure, antioxidant activity, and stability.

Ginsenosides are the primary active substance in ginseng plants and have a variety of benefits. However, its light and heat stability are weak and easy to decompose. This study used gum arabic (GA) and maltodextrin (MD) as wall materials, and 1% Tween 80 was used as emulsifier. Response surface methodology was used to optimize the preparation process of total saponins in the stems-leaves of Panax notoginseng (SLPNs) (SSLP) microcapsules by spray drying and freeze drying techniques. Under optimal process conditions, the two microcapsules have better solubility and lower moisture content (MC). The color of spray-dried SSLP microcapsules was greener and bluer, and the color was brighter. In morphology, the spray-dried SSLP microcapsules were spherical with a slightly shrunk surface, whereas the freeze-dried ones were lamellar and porous. The two microcapsules have strong stability under different storage conditions and in vitro gastrointestinal digestion simulation. In addition, both microcapsules and free SSLP contained multiple ginsenosides. At the same time, both microcapsules had good free radical scavenging ability. These results indicate that the microencapsulation technology could improve the stability and bioavailability of SSLP, which is expected to provide a reference for the intensive processing of the SLPN. PRACTICAL APPLICATION: After microencapsulation, the stem and leaf extract of Panax notoginseng improved its stability and taste, which laid a foundation for making more nutritious and better tasting food of the stem and leaf of P. notoginseng.

In Vivo and In Vitro Approaches to Modeling Hypoplastic Left Heart Syndrome.

PURPOSE OF REVIEW: Hypoplastic left heart syndrome (HLHS) is a critical congenital heart defect characterized by the underdevelopment of left-sided heart structures, leading to significant circulatory challenges, and necessitating multiple surgeries for survival. Despite advancements in surgical interventions, long-term outcomes often involve heart failure, highlighting the need for a deeper understanding of HLHS pathogenesis. Current in vivo and in vitro models aim to recapitulate HLHS anatomy and physiology, yet they face limitations in accuracy and complexity. RECENT FINDINGS: In vivo models, including those in chick, lamb, and mouse, provide insights into hemodynamic and genetic factors influencing HLHS. In vitro models using human induced pluripotent stem cells offer valuable platforms for studying genetic mutations and cellular mechanisms. This review evaluates these models' utility and limitations, and proposes future directions for developing more sophisticated models to enhance our understanding and treatment of HLHS.

Optimizing cooperative catalysis of multiple defective interfaces in Pt/mullite catalysts for NO oxidation.

Nitric oxide (NO) oxidation is an integral part of the nitrogen chemical cycle, but competitive activation of NO/O2 over single platinum (Pt)-based catalysts result in inadequate low temperature performance. Here, we constructed catalysts with BiMn2O5/CeO2 and Pt/BiMn2O5 defective interfaces (sufficient activation of NO/O2). The constructed catalyst achieved 95 % NO conversion at 260 °C in NO/O2 atmosphere, superior to most known catalysts. Even after aging (800 °C for 16 h), the NO conversion was up to 76 %. Further, the catalyst can be applied to actual diesel exhaust. Detailed oxygen vacancies (Ov) characterization reveals that BiMn2O5/CeO2 defective interface created by Ce3+-Ov + Mn4+-O ↔ Ce4+-O + Mn3+-Ov promote the activation of NO (on Mn3+ sites) and O2 (on Mn3+-Ov sites). Besides, the Ov on Pt/BiMn2O5 defective interface compensate for the loss of Pt sites ensuring hydrothermal stability. And this construction of multiple defective interfaces develops a pathway for boosting catalytic reactions.

Patterns of single and multiple HPV infections in female: A systematic review and meta-analysis.

Background: Data on the patterns of single and multiple HPV infections are largely limited to small size studies, and the regional difference have not been systematically examined. Methods: A literature search was conducted using PubMed, Embase, and Web of Science databases up to Sept 22, 2023. The pooled prevalence of HPV infection were calculated using random-effects meta-analysis. Subgroup analysis was used to explore the heterogeneity, and publication bias was evaluated by Egger's test and Begg's test. Results: There were 121 studies included with 1,682,422 participants. Globally, the most common genotypes of single HPV infection were HPV16 (7.05 %), 18 (1.94 %), 52 (1.93 %), 58 (1.68 %), and 31 (1.53 %), as well as HPV 16 (4.91 %), 31 (2.68 %), 52 (2.20 %), 51 (1.99 %), and 18 (1.96 %) in multiple HPV infections. Apart from HPV16 and 18, HPV52 and 58 were common in Asia, HPV31 and 51 was in Europe, North and South America, and HPV35 and 45 were in Africa. The prevalence of HPV infection among different age groups (<30, 30-50, >50 years age groups) was 20.93 %, 16.27 %, and 18.69 %, respectively. The single HPV infection prevalence in the No-ILs, LSILs, HSILs, and cervical cancer groups were 16.17 %, 51.60 %, 57.12 %, and 62.88 %, respectively, as well as in multiple infections were 5.09 %, 30.93 %, 32.86 %, and 21.26. Conclusion: Developing local HPV vaccines is necessary based on the HPV infection pattern. It is essential to educate young women to get vaccinated and encourage elderly women to have regular cervical cancer screenings to reduce the danger of cervical cancer.

EBV-Positive Classic Hodgkin Lymphoma and Primary Nodal T-Cell/NK-Cell Lymphoma Arising in the Background of Follicular Lymphoma.

EBV-positive primary nodal T-cell/NK cell lymphoma (TNKL) is a rare diagnosis with a poor prognosis. No relationship with follicular lymphoma (FL), classic Hodgkin lymphoma (cHL), or other non-Hodgkin lymphomas is established. We describe a case of Epstein-Barr virus (EBV)-positive cHL and EBV-positive primary nodal TNKL in the background of an antecedent FL, with all 3 subtypes identified in a single lymph node biopsy from an immunocompetent patient. Intensive frontline therapy achieved only a temporary response, with subsequent rapid progression associated with hemophagocytic lymphohistiocytosis (HLH). We discuss the relationship of the three lymphoma subtypes and the potential roles of EBV and immune dysregulation as contributing factors to this previously undescribed composite lymphoma.

Suppressed concentration quenching and tunable photoluminescence in Eu2+-activated Rb3Y(PO4)2 phosphors for full-spectrum lighting.

Highly efficient inorganic phosphors are desirable for lighting-emitting diode light sources, and increasing the doping concentration of activators is a common approach for enhancing the photoluminescence quantum yield (PLQY). However, the constraint of concentration quenching poses a great challenge for improving the PLQY. Herein, we propose a fundamental design principle by separating activators and prolonging their distance in Eu2+-activated Rb3Y(PO4)2 phosphors to inhibit concentration quenching, in which different quenching rates are controlled by the Eu distribution at various crystallographic sites. The blue-violet-emitting Rb3Y(PO4)2:xEu (x = 0.1%-15%) phosphors, with the occupation of Rb1, Rb2 and Y sites by Eu2+, exhibit rapid luminescence quenching with optimum external PLQY of 10% due to multi-channel energy migration. Interestingly, as the Eu concentration increases above 20%, Eu2+ prefer to occupy the Rb1 and Y sites with separated polyhedra and large interionic distances, resulting in green emission with suppressed concentration quenching, achieving an improved external PLQY of 41%. Our study provides a unique design perspective for elevating the efficiency of Eu2+-activated phosphors toward high-performance inorganic luminescent materials for full-spectrum lighting.

The anti-mCRP199-206 antibodies aggravate tubulointerstitial lesions in lupus nephritis.

Tubulointerstitial lesions could also be prominent in lupus nephritis, and the pathogenesis of tubulointerstitial lesions may be different from glomerular lesions. Previous studies have showed that plasma antibodies against modified /monomeric C-reactive protein (mCRP) are associated with renal tubulointerstitial lesions in patients with lupus nephritis, and amino acid (aa) 199-206 was one of the major epitopes of mCRP. However, the role of anti-mCRP199-206 antibodies in the pathogenesis of tubulointerstitial lesions in lupus nephritis is unknown. A total of 95 patients with renal biopsy-proven lupus nephritis were enrolled in this study. Plasma levels of anti-mCRP199-206 antibodies were screened by enzyme-linked immunosorbent assay (ELISA). A lupus prone mouse model was immunized using peptides mCRP199-206 to explore the potential role of anti-mCRP199-206 antibodies in tubulointerstitial lesions. The mechanism of anti-mCRP199-206 antibodies damage to renal tubular epithelial cells was investigated in vitro. Plasma antibodies against mCRP199-206 were associated with renal tubulointerstitial lesions and prognosis in patients with lupus nephritis. Immunization with peptides mCRP199-206 in lupus prone mice could aggravate tubulointerstitial lesions and drive tubulointerstitial inflammation and fibrosis. Anti-mCRP 199-206 antibodies could activate the TGF-ß1/Smad3 signal pathway and induce tubular damage by binding with CRP. Circulating antibodies against mCRP199-206 could be a biomarker to reveal tubulointerstitial lesion, and participate in the pathogenesis of tubulointerstitial lesions, which might provide a potential therapeutic target for lupus nephritis.

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

Identification and molecular mechanism of novel hypoglycemic peptide in ripened pu-erh tea: Molecular docking, dynamic simulation, and cell experiments.

Ripened pu-erh tea is known to have beneficial hypoglycemic properties. However, it remains unclear whether the bioactive peptides produced during fermentation are also related to hypoglycemic potential. This study aimed to identify hypoglycemic peptides in ripened pu-erh tea and to elucidate their bioactive mechanisms using physicochemical property prediction, molecular docking, molecular dynamics simulations, and cell experiments. Thirteen peptides were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, AADTDYRFS (AS-9) and AGDGTPYVR (AR-9) exhibited high α-glucosidase inhibitory activity, with half-maximal inhibitory concentration (IC50) values of 0.820 and 3.942 mg/mL, respectively. Molecular docking and dynamics simulations revealed that hydrogen bonding, hydrophobic interactions, and van der Waals forces assist peptides AS-9 and AR-9 in forming stable and tight complexes with α-glucosidase. An insulin-resistance (IR)-HepG2 cell model was established. AS-9 was non-toxic to IR-HepG2 cells and significantly increased the glucose consumption capacity, hexokinase, and pyruvate kinase activities of IR-HepG2 cells (p < 0.05). AS-9 alleviated glucose metabolism disorders and ameliorated IR by activating the IRS-1/PI3K/Akt signaling pathway and increasing the expression levels of MDM2, IRS-1, Akt, PI3K, GLUT4, and GSK3ß genes. In addition, no hemolysis of mice red blood cells red blood cells occurred at concentrations below 1 mg/mL. This work first explored hypoglycemic peptides in ripened pu-erh tea, providing novel insights for enhancing its functional value.

Comprehensive analysis of benzothiazoles (BTHs), benzotriazoles (BTRs), and benzotriazole ultraviolet absorbers (BUVs) in the western South China Sea: Spatial distributions, migration tendencies and ecotoxicological relevance.

Benzothiazoles (BTHs), benzotriazoles (BTRs), and benzotriazole ultraviolet absorbers (BUVs) have garnered significant attention owing to their persistent nature in the environment and adverse impacts on aquatic organisms. However, there remains a dearth of investigations and studies conducted in tropical marine environments. In this study, we undertook the inaugural distributional survey and ecotoxicological relevance of BTHs, BTRs, and BUVs in seawater and sediments of the western South China Sea (WSCS). Elevated concentrations of BTHs, BTRs, and BUVs in the seawater and suspended particulate matter (SPM) were primarily observed in the Pearl River Estuary (PRE) and the western region of the WSCS, attributed to terrestrial runoff and hydrodynamic processes. Moreover, the transport of these compounds at the seawater-SPM interface was influenced by both the intrinsic properties of the contaminants and temperature variations. Spatially, concentrations of BTHs, BTRs, and BUVs in surface sediments exhibited a diminishing trend with increasing distance from the coast to offshore areas, reflecting notable anthropogenic impacts. Concentration profiles of these compounds in sediment cores displayed a bottom-up increasing trend, with total organic carbon (TOC) identified as the primary determinant governing their accumulation within sediment cores in the WSCS. Terrestrial runoff inputs and atmospheric deposition as major contributors to the occurrence of BTHs, BTRs, and BUVs in the WSCS. Simultaneously, the study underscores the non-negligible moderate mixture risk quotient associated with BTHs, BTRs, and BUVs in the sediments.

Ionic liquid-assisted synthesis of In2O3 nanoparticles for ppb-level NO2 sensing at low temperature.

Highly sensitive detection of nitric dioxide (NO2) has recently attracted much attention due to its harmful to the human health even at a low concentration of 0.1 parts per million (ppm). Herein, In2O3 nanoparticles (NPs) were prepared via a facile ionic liquid (IL) assisted solvothermal method with subsequent calcination and then were analyzed through the characterization of X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption techniques. Morphological characterization demonstrated that the resultant compounds were In2O3 NPs with a diameter ranging from 20 to 30 nm. The gas sensor based on the In2O3 NPs prepared with IL exhibited excellent NO2-sensing properties in terms of fast response/recovery speed (26.6/10.0 s), high response (310.0), good repeatability and long-term stability to 10 ppm NO2 gas at low working temperature of 92 °C. The gas-sensing mechanism of In2O3 NPs to NO2 was represented to the surface adsorption control model and the possibilities relating to the improved NO2 sensing performance of the In2O3 NPs synthesized with IL-assisted were also discussed in detail.

Natural killer cells: a future star for immunotherapy of head and neck squamous cell carcinoma.

The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.