Spatially resolved mapping of cells associated with human complex traits.

Depicting spatial distributions of disease-relevant cells is crucial for understanding disease pathology. Here we present genetically informed spatial mapping of cells for complex traits (gsMap), a method that integrates spatial transcriptomics data with summary statistics from genome-wide association studies to map cells to human complex traits, including diseases, in a spatially resolved manner. Using embryonic spatial transcriptomics datasets covering 25 organs, we benchmarked gsMap through simulation and by corroborating known trait-associated cells or regions in various organs.

MWCNTs/PANI silk fibroin film sensor based on microneedle array for sweat pH detection.

Incorporating silk fibroin (SF) into the biosensing platform provides a level of flexibility and macro-structure control that holds immense importance for monitoring of sweat pH. It accomplishes non-invasive surveillance of the human physiology while concurrently tackling the issue of electrode-skin friction. The preparation of the multi-walled carbon nanotubes (MWCNTs)/polyaniline (PANI) silk fibroin pH-responsive microneedle array sensor involves the dispersion of PANI powder in silk fibroin and the addition of MWCNTs for the analysis of human sweat.

Cell-free epigenomes enhanced fragmentomics-based model for early detection of lung cancer.

Background: Lung cancer is a leading cause of cancer mortality, highlighting the need for innovative non-invasive early detection methods. Although cell-free DNA (cfDNA) analysis shows promise, its sensitivity in early-stage lung cancer patients remains a challenge. This study aimed to integrate insights from epigenetic modifications and fragmentomic features of cfDNA using machine learning to develop a more accurate lung cancer detection model.

From genetic associations to genes: methods, applications, and challenges.

Genome-wide association studies (GWASs) have identified numerous genetic loci associated with human traits and diseases. However, pinpointing the causal genes remains a challenge, which impedes the translation of GWAS findings into biological insights and medical applications. In this review, we provide an in-depth overview of the methods and technologies used for prioritizing genes from GWAS loci, including gene-based association tests, integrative analysis of GWAS and molecular quantitative trait loci (xQTL) data, linking GWAS variants to target genes through enhancer-gene connection maps, and network-based prioritization.

Mixed model-based deconvolution of cell-state abundances (MeDuSA) along a one-dimensional trajectory.

Deconvoluting cell-state abundances from bulk RNA-sequencing data can add considerable value to existing data, but achieving fine-resolution and high-accuracy deconvolution remains a challenge. Here we introduce MeDuSA, a mixed model-based method that leverages single-cell RNA-sequencing data as a reference to estimate cell-state abundances along a one-dimensional trajectory in bulk RNA-sequencing data. The advantage of MeDuSA lies primarily in estimating cell abundance in each state while fitting the remaining cells of the same type individually as random effects.

Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability.

Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status.

Type III Secretion System Repressor RhpR Induces GrlP, a Glycine-Rich Outer Membrane Lipoprotein with Functions in Regulating the Periplasmic Space and Pleiotropic Responses.

The two-component system RhpRS was initially identified as a regulator of genes encoding the type III secretion system (T3SS) in Pseudomonas syringae. Phosphorylated RhpR (P-RhpR) negatively regulates the T3SS genes by repressing the promoter, but directly activates the expression of a small gene named here as . Here, we show that is expressed higher in rich medium than in minimal medium in pv.

Comparative Efficacy of Pharmacological Therapies for Low Back Pain: A Bayesian Network Analysis.

Low back pain (LBP) is a common problem, but the efficacy of pharmacological therapies remains controversial. Therefore, we aimed to comprehensively evaluate and quantitatively rank various pharmacological therapies for patients with low back pain. Two meta-analyses were performed: an initial pair-wise meta-analysis, followed by network meta-analysis using a random-effects Bayesian model.

RIR1 represses plant immunity by interacting with mitochondrial complex I subunit in rice.

We previously observed decreased expression of rice OsmiR159a.1 on infection with the bacterial blight-causing pathogen Xanthomonas oryzae pv. oryzae (Xoo), and identified the OsLRR_RLK (leucine-rich repeat_ receptor like kinase) gene as an authentic target of OsmiR159a.

Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.

Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1 clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC of 1.

Two components of the rhpPC operon coordinately regulate the type III secretion system and bacterial fitness in Pseudomonas savastanoi pv. phaseolicola.

Many plant bacterial pathogens including Pseudomonas species, utilize the type III secretion system (T3SS) to deliver effector proteins into plant cells. Genes encoding the T3SS and its effectors are repressed in nutrient-rich media but are rapidly induced after the bacteria enter a plant or are transferred into nutrient-deficient media. To understand how the T3SS genes are regulated, we screened for P.

The Effect of Combination Pharmacotherapy on Low Back Pain: A Meta-analysis.

Objective: To evaluate the difference between combination pharmacotherapy and monotherapy on low back pain (LBP).

Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials databases up to March 14, 2017. Two authors independently extracted the data and assessed the validity of included trials.

A dual role for proline iminopeptidase in the regulation of bacterial motility and host immunity.

During plant-pathogen interactions, pathogenic bacteria have evolved multiple strategies to cope with the sophisticated defence systems of host plants. Proline iminopeptidase (PIP) is essential to Xanthomonas campestris pv. campestris (Xcc) virulence, and is conserved in many plant-associated bacteria, but its pathogenic mechanism remains unclear.

Preparation of decellularized biphasic hierarchical myotendinous junction extracellular matrix for muscle regeneration.

Unlabelled: Muscle injury and defect affect people's quality of life, and effective treatment is lacking. Herein, we generated a scaffold to obtain decellularized porcine Achilles tendon myotendinous junction (D-MTJ) extracellular matrix (ECM) with well-preserved native biphasic hierarchical structure, biological composition, and excellent mechanical properties for muscle regeneration. The combined use of potassium chloride, potassium iodide, Triton-X 100, and sodium-dodecyl sulfate (SDS) can completely remove the main immunogenicity, while maintaining the major biological components and microstructure.

Preparation and Evaluation of Tibia- and Calvarium-Derived Decellularized Periosteum Scaffolds.

The periosteum plays a key role in bone regeneration and an artificial bionic material is urgently required. The periostea on the tibia and skull differ with respect to the types of cells, microstructure, and components, leading to different biological functions and biomechanical properties. We aimed to prepare decellularized periosteum scaffolds derived from different origins and evaluate their angiogenic and osteogenic activities.

[Function of biofilms in phytopathogenic bacterial-host interactions].

Biofilms are complex three-dimensional bacterial assemblages that attach to biotic or abiotic solid surfaces, and frequently embed within a self-produced matrix of extracellular polymeric substances. Biofilm formation is a microbial defense response to biotic and abiotic stresses, and a key factor for survival in adverse environments. A wide variety of microorganisms can colonize distant tissues of higher plants, such as leaves, vascular network and roots, and adhere to the surface of the tissues to form biofilms.

Decellularized tendon as a prospective scaffold for tendon repair.

Tendon injuries impose significant clinical burdens on healthcare systems worldwide. At present, no therapeutic methods can cure tendon injuries in an ideal manner. With the development and improvement of decellularization technology, tendon extracellular matrix (ECM) can develop into novel scaffolds with potential for repairing injured tendons.