PD-L1-CD80 interactions are required for intracellular signaling necessary for dendritic cell migration.

Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration.

One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor.

Cancer immunotherapies rely on CD8 cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors.

Spherical harmonics texture extraction for versatile analysis of biological objects.

The characterization of phenotypes in cells or organisms from microscopy data largely depends on differences in the spatial distribution of image intensity. Multiple methods exist for quantifying the intensity distribution - or image texture - across objects in natural images. However, many of these texture extraction methods do not directly adapt to 3D microscopy data.

The calcitron: A simple neuron model that implements many learning rules via the calcium control hypothesis.

Theoretical neuroscientists and machine learning researchers have proposed a variety of learning rules to enable artificial neural networks to effectively perform both supervised and unsupervised learning tasks. It is not always clear, however, how these theoretically-derived rules relate to biological mechanisms of plasticity in the brain, or how these different rules might be mechanistically implemented in different contexts and brain regions. This study shows that the calcium control hypothesis, which relates synaptic plasticity in the brain to the calcium concentration ([Ca2+]) in dendritic spines, can produce a diverse array of learning rules.

Subunit-specific conductance of single homomeric and heteromeric HCN pacemaker channels at femtosiemens resolution.

In mammals, the four subunit isoforms HCN1-4 assemble to form functional homotetrameric and heterotetrameric hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels. Despite the outstanding relevance of HCN channels for organisms, including generating electrical rhythmicity in cardiac pacemaker cells and diverse types of brain neurons, key channel properties are still elusive. In particular, the unitary conductance, of HCN channels is highly controversial.

Bacterial sensor evolved by decreasing complexity.

Bacterial receptors feed into multiple signal transduction pathways that regulate a variety of cellular processes including gene expression, second messenger levels, and motility. Receptors are typically activated by signal binding to ligand-binding domains (LBDs). Cache domains are omnipresent LBDs found in bacteria, archaea, and eukaryotes, including humans.

Inotodiol induces hepatocellular carcinoma apoptosis by activation of MAPK/ERK pathway.

Hepatocellular carcinoma(HCC) has a high mortality and morbidity rate and seriously jeopardizes human life. Chemicals and chemotherapeutic agents have been experiencing problems such as side effects and drug resistance in the treatment of HCC, which cannot meet the needs of clinical treatment. Therefore, finding novel low-toxicity and high-efficiency anti-hepatocellular carcinoma drugs and exploring their mechanisms of action have become the current problems to be solved in the treatment of HCC.

Monitoring wetland cover changes and land surface temperatures using remote sensing and GIS in Göksu Delta.

Wetlands provide necessary ecosystem services, such as climate regulation and contribution to biodiversity at global and local scales, and they face spatial changes due to natural and anthropogenic factors. The degradation of the characteristic structure signals potential severe threats to biodiversity. This study aimed to monitor the long-term spatial changes of the Göksu Delta, a critical Ramsar site, using remote sensing techniques.

Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.

Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.

Decreased SynMuv B gene activity in response to viral infection leads to activation of the antiviral RNAi pathway in C. elegans.

RNA interference (RNAi) mediates antiviral defense in many eukaryotes. Caenorhabditis elegans mutants that disable RNAi are more sensitive to viral infection. Many mutants that enhance RNAi have also been identified; these mutations may reveal genes that are normally down-regulated in antiviral defense.

Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder.

Background: Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess this heterogeneity is to look for patterns in the subphenotype data.

Nitroxyl protects H9C2 cells from H/R-induced damage and inhibits autophagy via PI3K/Akt/mTOR pathway.

Background: Myocardial ischemia-reperfusion injury (MIRI) is an important complication in the treatment of heart failure, and its treatment has not made satisfactory progress. Nitroxyl (HNO) showed protective effects on the heart failure, however, the effect and underlying mechanism of HNO on MIRI remain largely unclear.

Methods: MIRI model in this study was established to induce H9C2 cell injury through hypoxia/reoxygenation (H/R) in vitro.

CAR-T entering a new "phase": Improving CAR-T function by harnessing phase separation.

Biomolecular condensation has emerged as a general principle in organizing biological processes, including immune response. Xu and colleagues recently reported that the cytoplasmic tail of the CD3ɛ subunit of TCR complex, when fused to CAR, can promote CAR condensation by liquid-liquid phase separation. Through sequence engineering, the authors identified modified CD3ɛ sequences that enhance the maturation of the immunological synapse and co-receptor signaling, leading to an improvement of cytotoxicity in vitro and anti-tumor effects in mouse xenograft models.

An Immune Subtype Classification System Enables the Development of Strategies to Predict and Enhance Immunotherapy Responses in Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality globally. While immunotherapeutic approaches are effective in a subset of CRC patients, the majority of CRC cases receive limited benefits from immunotherapy. This study developed an immune subtype classification system based on diverse immune cells and pathways.

Rectifying the Crosstalk between the Skeletal and Immune Systems Improves Osteoporosis Treatment by Core-Shell Nanocapsules.

Contemporary osteoporosis treatment often neglects the intricate interactions among immune cells, signaling proteins, and cytokines within the osteoporotic microenvironment. Here, we developed core-shell nanocapsules composed of a cationized lactoferrin core and an alendronate polymer shell. By tuning the size of these nanocapsules and leveraging the alendronate shell, we enabled precise delivery of small interfering RNA targeting the Semaphorin 4D gene (siSema4D) to specific bone sites.

Spiking Flip-Flop Memory in Resonant Tunneling Diode Neurons.

We report a spiking flip-flop memory mechanism that allows controllably switching between neural-like excitable spike-firing and quiescent dynamics in a resonant tunneling diode (RTD) neuron under low-amplitude (<150  mV pulses) and high-speed (ns rate) inputs pulses. We also show that the timing of the set-reset input pulses is critical to elicit switching responses between spiking and quiescent regimes in the system. The demonstrated flip-flop spiking memory, in which spiking regimes can be controllably excited, stored, and inhibited in RTD neurons via specific low-amplitude, high-speed signals (delivered at proper time instants) offers high promise for RTD-based spiking neural networks, with the potential to be extended further to optoelectronic implementations where RTD neurons and RTD memory elements are deployed alongside for fast and efficient photonic-electronic neuromorphic computing and artificial intelligence hardware.

Cross-trait GWAS in COVID-19 and systemic sclerosis reveals novel genes implicated in fibrotic and inflammation pathways.

Objectives: COVID-19 and systemic sclerosis (SSc) share multiple similarities in their clinical manifestations, alterations in immune response, and therapeutic options. These resemblances have also been identified in other immune-mediated inflammatory diseases where a common genetic component has been found. Thus, we decided to evaluate for the first time this shared genetic architecture with SSc.

Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation.

The objective of this study was to investigate the cardioprotective effects of Munziq on abnormal body fluid myocardial ischemia-reperfusion injury (MIRI) and its underlying mechanism.Normal rats and rats with abnormal body fluid (ABF) were pre-treated with Munziq for 21 days. Following this, MIRI models were established.

S100A8 regulates postoperative responses following tooth extraction in rats.

The reduction in alveolar ridge height and width after tooth extraction poses a substantial challenge for dental implant restoration. This study aimed to observe the roles of S100A8 in the inflammatory response and bone resorption following tooth extraction. Rat mandibular second molars were extracted.

Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1/PGC-1α pathway.

Background: Acute systemic inflammation affects many organs and it occurs in a wide range of conditions such as acute lung injury (ALI). Inflammation-triggered oxidative pathways together with the caspase activation seen in ALI, result in apoptosis. Dapagliflozin (DPG) is an agent that is known to have oxidative stress-reducing and anti-inflammatory effects in many tissues.

Distinct TYRO3 and PROS1 expression levels contribute to preeclampsia pathogenesis.

Preeclampsia (PE) is a severe placental complication occurring after the 20th week of pregnancy. PE is associated with inflammation and an increased immune reaction against the fetus. TYRO3 and PROS1 suppress inflammation by clearing apoptotic cells.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.

Bright and Specific Targeting of Metastatic Lymph Nodes in Orthotopic Mouse Models of Gastric Cancer with a Fluorescent Anti-CEA Antibody.

Background: Gastric cancer poses a major diagnostic and therapeutic challenge. Improved visualization of tumor margins and lymph node metastases with tumor-specific fluorescent markers could improve outcomes.

Methods: To establish orthotopic models of gastric cancer, one million cells of the human gastric cancer cell line, MKN45, were suspended in 50 μl of equal parts PBS and Matrigel and injected into the nude mouse stomach with a 29-gauge needle.

Therapeutic potential and underlying mechanisms of phytoconstituents: emphasizing on resveratol, curcumin, quercetin, berberine, and hesperidin in ulcerative colitis.

Ulcerative colitis is a long-term inflammatory colon illness that significantly affects patients quality of life. Traditional medicines and therapies often come with challenges such as side effects, instability, unpredictability, and high costs. This has captured interest in natural products that have huge health benefits.

Tinosinenside A inhibits neuroinflammation and protects HT22 cells by suppressing the TLR4/NF-κB/NLRP3 signaling pathway in BV2 cells.

Microglia-mediated neuroinflammation plays a crucial role in Alzheimer's disease (AD). Tinosinenside A (Tis A) is a novel sesquiterpene glycoside isolated from the dried rattan stem of Tinospora sinensis (Lour.) Merr.