Efficacy and safety of telitacicept in patients with lupus nephritis.

Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self-controlled before-after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12-48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI-2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m2) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID-19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis.

Organ-specific immunity: A tissue analysis framework for investigating local immune responses to SARS-CoV-2.

Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.

Erratum: Publisher's Note: "Magnetic force-based cell manipulation for in vitro tissue engineering" [APL Bioeng. 7, 031504 (2023)].

[This corrects the article DOI: 10.1063/5.0138732.].

Magnetic force-based cell manipulation for in vitro tissue engineering.

Cell manipulation techniques such as those based on three-dimensional (3D) bioprinting and microfluidic systems have recently been developed to reconstruct complex 3D tissue structures in vitro. Compared to these technologies, magnetic force-based cell manipulation is a simpler, scaffold- and label-free method that minimally affects cell viability and can rapidly manipulate cells into 3D tissue constructs. As such, there is increasing interest in leveraging this technology for cell assembly in tissue engineering. Cell manipulation using magnetic forces primarily involves two key approaches. The first method, positive magnetophoresis, uses magnetic nanoparticles (MNPs) which are either attached to the cell surface or integrated within the cell. These MNPs enable the deliberate positioning of cells into designated configurations when an external magnetic field is applied. The second method, known as negative magnetophoresis, manipulates diamagnetic entities, such as cells, in a paramagnetic environment using an external magnetic field. Unlike the first method, this technique does not require the use of MNPs for cell manipulation. Instead, it leverages the magnetic field and the motion of paramagnetic agents like paramagnetic salts (Gadobutrol, MnCl2, etc.) to propel cells toward the field minimum, resulting in the assembly of cells into the desired geometrical arrangement. In this Review, we will first describe the major approaches used to assemble cells in vitro-3D bioprinting and microfluidics-based platforms-and then discuss the use of magnetic forces for cell manipulation. Finally, we will highlight recent research in which these magnetic force-based approaches have been applied and outline challenges to mature this technology for in vitro tissue engineering.

Molecular Spring Constant Analysis by Biomembrane Force Probe Spectroscopy.

A biomembrane force probe (BFP) has recently emerged as a native-cell-surface or in situ dynamic force spectroscopy (DFS) nanotool that can measure single-molecular binding kinetics, assess mechanical properties of ligand-receptor interactions, visualize protein dynamic conformational changes and more excitingly elucidate receptor mediated cell mechanosensing mechanisms. More recently, BFP has been used to measure the spring constant of molecular bonds. This protocol describes the step-by-step procedure to perform molecular spring constant DFS analysis. Specifically, two BFP operation modes are discussed, namely the Bead-Cell and Bead-Bead modes. This protocol focuses on deriving spring constants of the molecular bond and cell from DFS raw data.

Plasmonic tweezers for optical manipulation and biomedical applications.

Plasmonic tweezers are an emerging research topic because of their breakthrough in the conventional diffraction limit and precise manipulation at the nanoscale. Notably, their compatibility with analytical techniques (e.g. fluorescence, surface-enhanced Raman scattering (SERS), and laser desorption/ionization mass spectrometry (LDI MS)) opens up opportunities in optical manipulation and biomedical applications. Herein, we first introduce the structures and trapping forces, followed by a summary of the properties of plasmonic tweezers. The optical trapping of biosamples by plasmonic tweezers are then reviewed, including microorganisms and biomolecules. Finally, we highlight the integration of plasmonic tweezers with analytical techniques towards bioanalytical applications. We conclude with perspectives on the future directions for this topic. We foresee the upcoming era of biological detection by plasmonic tweezing in both academy and industry, which calls for the interest and efforts of scientists from diverse fields.

Supplementary data for the mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radical.

The data presented in this article are related to the research article entitled "The mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radical" (Dai et al., 2017) [1]. This article includes the structures of three kinds of disaccharides such as maltose, fructose and cellobiose, the diagrammatic sketch of the hydrogen abstraction reaction of the disaccharides by hydroxyl radical, the structure of the transition states for pyran ring opening of moiety A and cleavage of α(1→2) glycosidic bond starting from the hydrogen abstraction of C6-H in moiety A of sucrose, the transition state structure for cleavage of α(1→2) glycosidic bond starting from the hydrogen abstraction of C1'-H in moiety B of sucrose, the transition state structure, sketch for the reaction process and relative energy change of the reaction pathway for direct cleavage of α(1→4) glycosidic bond starting from hydrogen abstraction of C6'-H of moiety B of maltose.

The mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radical.

A novel mechanism for cleavage of three typical α(1→2), α(1→4) and ß(1→4) glucosidic bonds induced by hydroxyl free radical was examined with DFT theory at B3LYP/6-31+G(d,p) level using PCM water solvent model. It was found that the hydrogen abstraction from the CH bonds outside the saccharide rings could induce the hydrogen transfer from the hydroxyl at the radical carbon to the oxygen atom of saccharide ring with the mediation of water, which led to the opening of saccharide ring and the breakage of glucosidic bonds. Alternatively, the hydrogen in COH outside the saccharide ring of maltose and sucrose could also transfer to the adjacent glucosidic oxygen atom with a water molecule mediation to make glucosidic bond break directly. Based on this study, it can be well explained the experimental results that the oxidation of some oligosaccharides with hydroxyl free radicals can produce molecules of glucose, fructose and other monosaccharides.