FcRn-guided antigen trafficking enhances cancer vaccine efficacy.

The development of tumor vaccines represents a significant focus within cancer therapeutics research. Nonetheless, the efficiency of antigen presentation in tumor vaccine remains suboptimal. We introduce an innovative mRNA-lipid nanoparticle platform designed to express tumor antigenic epitopes fused with the transmembrane domain and cytoplasmic tail of the neonatal Fc receptor (FcRn).

A bispecific antibody targeting the Ig domains of Siglec-E displays enhanced antitumor effects.

Siglec-9 is a promising immune checkpoint molecule, and therapeutics targeting Siglec-9 have the potential to augment anti-tumor immunity. Here, we generated a bispecific antibody, named as aSE4-1-Fc, by fusing two distinct alpaca derived nanobodies, which can simultaneously target the extracellular Ig variable (V)-set domain and C2-set domains of murine Siglec-9 (also known as Siglec-E) with high affinity. In vivo studies showed that aSE4-1-Fc was better than its component antibodies in inhibiting tumor growth/metastasis, and Siglec-E blockade using aSE4-1-Fc generated protective anti-tumor T cell memory.

ROR1/STAT3 positive feedback loop facilitates cartilage degeneration in Osteoarthritis through activation of NF-κB signaling pathway.

Background: Osteoarthritis (OA) is a chronic joint disorder with a serious impact on society. The main pathological change in OA is articular cartilage degeneration, which is directly associated with imbalance of anabolic and catabolic activities in chondrocytes.

Objective: To evaluate the expression and biological effects of ROR1 in OA cartilage and determine whether knockdown of ROR1 attenuates cartilage degeneration.

The new progress in cancer immunotherapy.

The cross talk between immune and non-immune cells in the tumor microenvironment leads to immunosuppression, which promotes tumor growth and survival. Immunotherapy is an advanced treatment that boosts humoral and cellular immunity rather than using chemotherapy or radiation-based strategy associated with non-specific targets and toxic effects on normal cells. Immune checkpoint inhibitors and T cell-based immunotherapy have already exhibited significant effects against solid tumors and leukemia.

Intense ocean freshening from melting glacier around the Antarctica during early twenty-first century.

With the accelerating mass loss of Antarctic ice sheets, the freshening of the Southern Ocean coastal oceans (SOc, seas around Antarctica) is gradually intensifying, which will reduce the formation of bottom water and weaken the meridional overturning circulation, thus having a significant negative impact on the ocean's role in regulating global climate. Due to the extreme environment of the Southern Ocean and the limitations of observational techniques, our understanding of the glacier-derived freshening of SOc is still vague. We developed a method that first provided us with an expansive understanding of glacier-derived freshening progress over the SOc.

Hierarchically porous activated carbons prepared a dissipative process: a high-capacity cathode for Li-ion capacitors.

Activated carbons with high specific surface area (SSA) and well-modulated pore structure are highly desirable for achieving high-performance capacitive energy storage. Herein, hierarchically porous activated carbons (PACs) are synthesized by a tableting-activation method. The quick release of high-pressure gaseous products from the inside of the tablets can be regarded as a dissipative process, which leads to the formation of well-ordered high density meso- or macropores in the resulting material.

Isolation and Detection of Murine iNKT Cells in Different Organs.

The invariant NKT (iNKT) cells are innate-like lymphocytes that share phenotypic and functional characteristics with NK cells and T cells, playing an important role in both human and mouse physiology and disease and bridging the gap between the innate and adaptive immune responses. The frequency and subtypes of iNKT cells in major immune organs are different, which also determines the regional immune characteristics of iNKT cells. Here, we report a protocol about the isolation of iNKT cells in the thymus, spleen, and liver of C57BL/6, CD1d, and Jα18 mice.

Evaluation and Comparison of Serological Methods for COVID-19 Diagnosis.

The worldwide pandemic of COVID-19 has become a global public health crisis. Various clinical diagnosis methods have been developed to distinguish COVID-19-infected patients from healthy people. The nucleic acid test is the golden standard for virus detection as it is suitable for early diagnosis.

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis.

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way.

Endometrial cavity fluid is associated with deleterious pregnancy outcomes in patients undergoing fertilization/intracytoplasmic sperm injection: a retrospective cohort study.

Background: The effects of endometrial cavity fluid (ECF) on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancy outcomes following embryo transfer (ET) are still controversial. We conducted the present study to investigate whether the presence of ECF in infertile patients scheduled to undergo IVF or ICSI was associated with pregnancy outcomes.

Methods: A retrospective cohort study design was used.

Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation.

Diagnosed in more than 90% of cervical cancers, the fourth deadliest cancer in women, human papillomavirus (HPV) is currently the most common pathogen responsible for female cancers. Moreover, HPV infection is associated with many other diseases, including cutaneous and anogenital warts, and genital and upper aerodigestive tract cancers. The incidence and prevalence of these pathologies vary considerably depending on factors including HPV genotype, regional conditions, the study population, and the anatomical site sampled.

Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome.

Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD-CARD interaction between purified NLRP1 and ASC experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution.

Molecular and Structural Basis of DNA Sensors in Antiviral Innate Immunity.

DNA viruses are a source of great morbidity and mortality throughout the world by causing many diseases; thus, we need substantial knowledge regarding viral pathogenesis and the host's antiviral immune responses to devise better preventive and therapeutic strategies. The innate immune system utilizes numerous germ-line encoded receptors called pattern-recognition receptors (PRRs) to detect various pathogen-associated molecular patterns (PAMPs) such as viral nucleic acids, ultimately resulting in antiviral immune responses in the form of proinflammatory cytokines and type I interferons. The immune-stimulatory role of DNA is known for a long time; however, DNA sensing ability of the innate immune system was unraveled only recently.

Diagnostic accuracy of serological tests and kinetics of severe acute respiratory syndrome coronavirus 2 antibody: A systematic review and meta-analysis.

This study aimed to assess the diagnostic test accuracy (DTA) of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) serological test methods and the kinetics of antibody positivity. Systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We included articles evaluating the diagnostic accuracy of serological tests and the kinetics of antibody positivity.

IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology.

The barrier surfaces of the gastrointestinal tract are in constant contact with various microorganisms. Cytokines orchestrate the mucosal adaptive and innate immune cells in the defense against pathogens. IL-10 and IL-22 are the best studied members of the IL-10 family and play essential roles in maintaining mucosal homeostasis.

Pharmacological Inhibitors of the NLRP3 Inflammasome.

Inflammasomes play a crucial role in innate immunity by serving as signaling platforms which deal with a plethora of pathogenic products and cellular products associated with stress and damage. By far, the best studied and most characterized inflammasome is NLRP3 inflammasome, which consists of NLRP3 (nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3), ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and procaspase-1. Activation of NLRP3 inflammasome is mediated by highly diverse stimuli.

Interleukin-10 Family Cytokines Immunobiology and Structure.

The Interleukin (IL)-10 cytokine family includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26, which are considered as Class 2α-helical cytokines. IL-10 is the most important cytokine in suppressing pro-inflammatory responses in all kinds of autoimmune diseases and limiting excessive immune responses. Due to protein structure homology and shared usage of receptor complexes as well as downstream signaling pathway, other IL-10 family cytokines also show indispensable functions in immune regulation, tissue homeostasis, and host defense.

Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling.

Objective: Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined.

IL-6 Promotes T Cell Proliferation and Expansion under Inflammatory Conditions in Association with Low-Level RORγt Expression.

IL-6 is a critical driver of acute and chronic inflammation and has been reported to act as a T cell survival factor. The influence of IL-6 on T cell homeostasis is not well resolved. We demonstrate that IL-6 signaling drives T cell expansion under inflammatory conditions but not during normal homeostasis.

Autoimmune susceptibility imposed by public TCRβ chains.

Although the TCR repertoire is highly diverse, a small fraction of TCR chains, referred to as public, preferentially form and are shared by most individuals. Prior studies indicated that public TCRβ may be preferentially deployed in autoimmunity. We hypothesized that if these TCRβ modulate the likelihood of a TCRαβ heterodimer productively engaging autoantigen, because they are widely present in the population and often high frequency within individual repertoires, they could also broadly influence repertoire responsiveness to specific autoantigens.

Differential T Cell Cytokine Receptivity and Not Signal Quality Distinguishes IL-6 and IL-10 Signaling during Th17 Differentiation.

How a large number of cytokines differentially signal through a small number of signal transduction pathways is not well resolved. This is particularly true for IL-6 and IL-10, which act primarily through STAT3 yet induce dissimilar transcriptional programs leading alternatively to pro- and anti-inflammatory effects. Kinetic differences in signaling, sustained to IL-10 and transient to IL-6, are critical to this in macrophages.

Evaluation of Empirical Tropospheric Models Using Satellite-Tracking Tropospheric Wet Delays with Water Vapor Radiometer at Tongji, China.

An empirical tropospheric delay model, together with a mapping function, is commonly used to correct the tropospheric errors in global navigation satellite system (GNSS) processing. As is well-known, the accuracy of tropospheric delay models relies mainly on the correction efficiency for tropospheric wet delays. In this paper, we evaluate the accuracy of three tropospheric delay models, together with five mapping functions in wet delays calculation.