SOX2-induced IL1α-mediated immune suppression drives epithelial dysplasia malignant transformation.

Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return.

SpatialCTD: A Large-Scale Tumor Microenvironment Spatial Transcriptomic Dataset to Evaluate Cell Type Deconvolution for Immuno-Oncology.

Recent technological advancements have enabled spatially resolved transcriptomic profiling but at a multicellular resolution that is more cost-effective. The task of cell type deconvolution has been introduced to disentangle discrete cell types from such multicellular spots. However, existing benchmark datasets for cell type deconvolution are either generated from simulation or limited in scale, predominantly encompassing data on mice and are not designed for human immuno-oncology.

Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium.

Virus-induced cell death is a key contributor to COVID-19 pathology. Cell death induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well studied in myeloid cells but less in its primary host cell type, angiotensin-converting enzyme 2 (ACE2)-expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis in HAE organotypic cultures.

Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy.

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models.

Photophobia and Visual Triggers in Vestibular Migraine.

Introduction: Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo. However, the relationship between photophobia and visual triggers in VM remains unexplored. We investigated the correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM.

Clustering and visualization of single-cell RNA-seq data using path metrics.

Recent advances in single-cell technologies have enabled high-resolution characterization of tissue and cancer compositions. Although numerous tools for dimension reduction and clustering are available for single-cell data analyses, these methods often fail to simultaneously preserve local cluster structure and global data geometry. To address these challenges, we developed a novel analyses framework, Single-Cell Path Metrics Profiling (scPMP), using power-weighted path metrics, which measure distances between cells in a data-driven way.

Factors associated with health behaviours among stroke survivors: A mixed-methods study using COM-B model.

Aims: To identify factors associated with health behaviours among stroke survivors, through a multi-centre study.

Design: A sequential mixed methods design.

Methods: In the quantitative research phase, a total of 350 participants were recruited through multi-stage sampling from December 2022 to June 2023.

DANCE: a deep learning library and benchmark platform for single-cell analysis.

DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line.

Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8 T Cell Fitness for Antitumor Immunity.

According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8 T cell-mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA-mediated CD8 T cell activation.

Backbone cyclization of Salmonella typhimurium diaminopropionate ammonia-lyase to enhance the activity and stability.

Diaminopropionate ammonia-lyase transforms D and L isomers of 2,3-diaminopropionate to pyruvate and ammonia. It catalyzes D- and l-serine less effectively. L-2,3-diaminopropionate is a precursor in the biosynthesis of oxalyl diaminopropionate as a neurotoxin in certain legume species.

Single-Cell Multimodal Prediction via Transformers.

The recent development of multimodal single-cell technology has made the possibility of acquiring multiple omics data from individual cells, thereby enabling a deeper understanding of cellular states and dynamics. Nevertheless, the proliferation of multimodal single-cell data also introduces tremendous challenges in modeling the complex interactions among different modalities. The recently advanced methods focus on constructing static interaction graphs and applying graph neural networks (GNNs) to learn from multimodal data.

Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFR mutation.

Dual- or multi-targeted EGFR inhibitors as single drugs can overcome EGFR inhibitor resistance and circumvent many disadvantages of combination therapy. In this work, fifteen 4-anilinoquinazoline derivatives bearing nitrogen mustard or hemi mustard moieties were designed and synthesized as dual EGFR-DNA targeting anticancer agents. Structures of target molecules were confirmed by H NMR, C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay.

Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING.

Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation.

Effect of laser-assisted reconstructive surgical therapy of peri-implantitis on protein biomarkers and bacterial load.

Objectives: This randomized clinical trial assessed changes in protein biomarker levels and bacterial profiles after surgical reconstructive therapy of peri-implantitis and investigated whether the adjunctive use of Er:YAG laser impacts protein biomarker and microbial outcomes.

Materials And Methods: Twenty-four patients received surgical reconstructive therapy for peri-implantitis with guided bone regeneration following mechanical debridement with (test) or without (control) the adjunctive irradiation of Er:YAG laser. Bacterial and peri-implant crevicular fluid (PICF) samples were collected over 6 months and analyzed with bacterial qPCR and luminex multiplex assays.

An analysis of classical multidimensional scaling with applications to clustering.

Classical multidimensional scaling is a widely used dimension reduction technique. Yet few theoretical results characterizing its statistical performance exist. This paper provides a theoretical framework for analyzing the quality of embedded samples produced by classical multidimensional scaling.

An overview of deterministic and probabilistic forecasting methods of wind energy.

In recent years, a variety of wind forecasting models have been developed, prompting necessity to review the abundant methods to gain insights of the state-of-the-art development status. However, existing literature reviews only focus on a subclass of methods, such as multi-objective optimization and machine learning methods while lacking the full particulars of wind forecasting field. Furthermore, the classification of wind forecasting methods is unclear and incomplete, especially considering the rapid development of this field.

An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2.

Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes.

OXPHOS promotes apoptotic resistance and cellular persistence in T17 cells in the periphery and tumor microenvironment.

T cell proliferation and cytokine production are bioenergetically and biosynthetically costly. The inability to meet these metabolic demands results in altered differentiation, accompanied by impaired effector function, and attrition of the immune response. Interleukin-17-producing CD4 T cells (T17s) are mediators of host defense, autoimmunity, and antitumor immunity in the setting of adoptive T cell therapy.

Changes in salivary biomarkers associated with periodontitis and diabetic neuropathy in individuals with type 1 diabetes.

The objective of this pilot clinical study was to identify salivary biomarkers that are associated with periodontal disease and measures of diabetic autonomic dysfunction. Saliva samples from 32 participants were obtained from 3 groups: healthy (H), type 1 diabetes mellitus (DM), and type 1 diabetes mellitus with neuropathy (DMN). Based on the periodontal examination, individuals' mean Periodontal Screening and Recording scores were categorized into two groups (periodontally healthy and gingivitis), and correlated to specific salivary inflammatory biomarkers assessed by a customized protein array and enzyme assay.

Theoretical modeling of ice lithography on amorphous solid water.

Due to the perfection of the nanofabrication in nanotechnology and nanoscience, ice lithography (IL) by patterning ice thin-films with a focused electron beam, as a significant derivative technology of electron beam lithography (EBL), is attracting growing attention, evoked by its advantages over traditional EBL with respects of -fabrication, high efficiency, high accuracy, limited proximity effect, three-dimensional (3D) profiling capability, . However, theoretical modeling of ice lithography for replicated profiles on the ice resist (amorphous solid water, ASW) has rarely been reported so far. As the result, the development of ice lithography still stays at the experimental stage.

Supervised capacity preserving mapping: a clustering guided visualization method for scRNA-seq data.

Motivation: The rapid development of scRNA-seq technologies enables us to explore the transcriptome at the cell level on a large scale. Recently, various computational methods have been developed to analyze the scRNAseq data, such as clustering and visualization. However, current visualization methods, including t-SNE and UMAP, are challenged by the limited accuracy of rendering the geometric relationship of populations with distinct functional states.

Cancer-specific type-I interferon receptor signaling promotes cancer stemness and effector CD8+ T-cell exhaustion.

Type-I interferon (IFN-I) signaling is critical to maintaining antigen-presenting cell function for anti-tumor immunity. However, recent studies have suggested that IFN-I signaling may also contribute to more aggressive phenotypes, raising the possibility that IFN-I downstream signaling in cancer and myeloid cells may exert dichotomous functions.We analyzed the clinicopathologic correlation of cancer-specific IFN-I activation in 195 head and neck squamous cell carcinoma patients.

Dual light-driven p-ZnFeO/n-TiO catalyst: Benzene-breaking reaction for malachite green.

Heterocyclic aromatic compounds such as malachite green can cause immense harm to the environment and mankind because of their toxic bio-accumulation and insufficient biodegradation. ZnFeO/TiO (ZF-T) has attracted attentions as a visible-light-driven catalyst because it can break and mineralize benzene through photolysis. Compared with TiO, which photodegrades only 53.

Machine learning-assisted immune profiling stratifies peri-implantitis patients with unique microbial colonization and clinical outcomes.

The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling.