Novel genetically engineered silk materials for recycling polyethylene terephthalate (PET) plastic waste.

Polyethylene terephthalate (PET) is a widely used plastic whose poor degradability has led to serious environmental pollution. In recent years, it was shown that the engineered enzyme FAST-PETase can efficiently catalyze the hydrolysis of PET into monomers; however, large-scale production and low-cost application of this enzyme remain challenging. In this study, we successfully produced FAST-PETase at a large scale using the silk gland expression system of Bombyx mori and integrated an optimized FAST-PETase gene into the B.

Advances in research on SATB2 and its role in tumor development.

SATB2 is an AT-rich DNA-binding protein with a highly restricted expression pattern, primarily found in the brain, digestive tract, bone, and immune system, making it a promising target for medical research and clinical applications. Dysregulation or mutations in SATB2 have been implicated in various conditions, including cancers, isolated cleft palate, and SATB2-associated syndrome (SAS). This review aims to provide a comprehensive summary of the structure, biological functions, and potential role of SATB2 in tumor development.

Impact of polymorphisms on gene expression and splicing in response to exercise and diet-induced weight loss in human skeletal muscle tissues.

Weight loss through exercise and diet reduces the risk of type 2 diabetes, but the genetic regulation of gene expression and splicing in response to weight loss remains unclear in humans. We collected clinical data and skeletal muscle biopsies from 54 overweight/obese Asian individuals before and after a 16-week lifestyle intervention, which resulted in an average of ∼10% weight loss, accompanied by an ∼30% increase in insulin-stimulated glucose uptake. Improvements were observed in 118 of 252 clinical traits and six blood lipids.

Asian diversity in human immune cells.

The relationships of human diversity with biomedical phenotypes are pervasive yet remain understudied, particularly in a single-cell genomics context. Here, we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 donors, spanning 7 population groups across 5 Asian countries, and 6 controls.

Resonance light scattering combined with miniaturized Thermal-Assisted Purge-and-Trap device for screening of hydrochloride drugs.

Resonance Light Scattering (RLS) is a sensitive analytical technology hindered by its susceptibility to impurities in complex samples. This study introduces a combination of RLS with a high-efficiency sample preparation device, the Miniaturized Thermal-Assisted Purge-and-Trap (MTAPT), enhancing RLS's effectiveness in complex sample analysis. Specifically, we utilized MTAPT-RLS for the indirect screening of illegal hydrochloride drug additions in health products, based on three considerations: the transformation of bound HCl in hydrochloride drugs into volatile HCl under strong acid and heat; the minimal Cl content in health products for taste purposes; and the detectability of Cl ions by RLS upon the addition of AgNO and a stabilizer.

An Efficient Biosynthetic System for Developing Functional Silk Fibroin-Based Biomaterials.

Long historical evolution and domestication endow silkworms with the super ability to synthesize and secrete massive silk proteins using silk glands. The major component of this secretion consists of silk fibroin, considered a promising biomaterial for tissue repairs and engineering. To further expand the utility of this unique protein, there is a continuing need for silk fibroin functionalization.

Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases.

Alternative splicing contributes to complex traits, but whether this differs in trait-relevant cell types across diverse genetic ancestries is unclear. Here we describe cell-type-specific, sex-biased and ancestry-biased alternative splicing in ~1 M peripheral blood mononuclear cells from 474 healthy donors from the Asian Immune Diversity Atlas. We identify widespread sex-biased and ancestry-biased differential splicing, most of which is cell-type-specific.

CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury.

Wnt/β-catenin signaling is an attractive target for regenerative medicine. A powerful driver of stem cell activity and hence tissue regeneration, Wnt signaling can promote fibroblast proliferation and activation, leading to fibrosis, while prolonged Wnt signaling is potentially carcinogenic. Thus, to harness its therapeutic potential, the activation of Wnt signaling must be transient, reversible, and tissue specific.

Multiplex qPCR development for the simultaneous and rapid detection of largemouth bass virus and infectious spleen and kidney necrosis virus in aquaculture.

Largemouth bass virus (LMBV) and infectious spleen and kidney necrosis virus (ISKNV) are both belong to Iridoviridae that cause considerable economic losses in the fish industry. There is no reported literature that can detect these two viruses simultaneously. In this study, we established a multiplex quantitative polymerase chain reaction (qPCR) assay that can specifically and simultaneously detect both LMBV and ISKNV in fish samples.

Expanding RNA editing toolkit using an IDR-based strategy.

RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient.

Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines.

Human cancer cell lines have long served as tools for cancer research and drug discovery, but the presence and the source of intra-cell-line heterogeneity remain elusive. Here, we perform single-cell RNA-sequencing and ATAC-sequencing on 42 and 39 human cell lines, respectively, to illustrate both transcriptomic and epigenetic heterogeneity within individual cell lines. Our data reveal that transcriptomic heterogeneity is frequently observed in cancer cell lines of different tissue origins, often driven by multiple common transcriptional programs.

A Novel Approach for Screening Sericin-Derived Therapeutic Peptides Using Transcriptomics and Immunoprecipitation.

With the demand for more efficient and safer therapeutic drugs, targeted therapeutic peptides are well received due to their advantages of high targeting (specificity), low immunogenicity, and minimal side effects. However, the conventional methods of screening targeted therapeutic peptides in natural proteins are tedious, time-consuming, less efficient, and require too many validation experiments, which seriously restricts the innovation and clinical development of peptide drugs. In this study, we established a novel method of screening targeted therapeutic peptides in natural proteins.

Vehicle crash simulations for safety: Introduction of connected and automated vehicles on the roadways.

Traffic accidents are one main cause of human fatalities in modern society. With the fast development of connected and autonomous vehicles (CAVs), there comes both challenges and opportunities in improving traffic safety on the roads. While on-road tests are limited due to their high cost and hardware requirements, simulation has been widely used to study traffic safety.

A novel method for silkworm cocoons self-degumming and its effect on silk fibers.

Introduction: Conventional hot-alkaline cocoon degumming techniques greatly weaken the physicochemical and mechanical properties of silk fibroin fiber, thus affecting the quality of silk fabric. Moreover, it causes massive energy waste and serious environmental pollution.

Objective: This study aims to establish a novel cocoon self-degumming method by genetic modification of silkworm varieties and silk fibers.

ping the Perturb-Atlas.

A key objective of the research in the postgenomic era is to decipher the functions of the mammalian genome, which has remained largely enigmatic despite intensive efforts in the functional genomics field over the past two decades. To attack this problem, we have combined the CRISPR-Cas and Cre-Lox technologies to develop iMAP (inducible Mosaic Animal for Perturbation), a transformative tool for rapidly unraveling mammalian genome function . Furthermore, we have used iMAP to rapidly construct a "Perturb-Atlas" profiling the functions of 90 protein-coding genes across 39 tissues in mice, which has offered rich insights into gene functions difficult to readily obtain using conventional mouse gene-targeting models.

The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling.

DPF3, a component of the SWI/SNF chromatin remodeling complex, has been associated with clear cell renal cell carcinoma (ccRCC) in a genome-wide association study. However, the functional role of DPF3 in ccRCC development and progression remains unknown. In this study, we demonstrate that DPF3a, the short isoform of DPF3, promotes kidney cancer cell migration both in vitro and in vivo, consistent with the clinical observation that DPF3a is significantly upregulated in ccRCC patients with metastases.

Large-scale multiplexed mosaic CRISPR perturbation in the whole organism.

Here, we report inducible mosaic animal for perturbation (iMAP), a transgenic platform enabling in situ CRISPR targeting of at least 100 genes in parallel throughout the mouse body. iMAP combines Cre-loxP and CRISPR-Cas9 technologies and utilizes a germline-transmitted transgene carrying a large array of individually floxed, tandemly linked gRNA-coding units. Cre-mediated recombination triggers expression of all the gRNAs in the array but only one of them per cell, converting the mice to mosaic organisms suitable for phenotypic characterization and also for high-throughput derivation of conventional single-gene perturbation lines via breeding.

A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice.

The 5-methylcytosine (m5C) modification on an mRNA molecule is deposited by Nsun2 and its paralog Nsun6. While the physiological functions of Nsun2 have been carefully studied using gene knockout (KO) mice, the physiological functions of Nsun6 remain elusive. In this study, we generated an Nsun6-KO mouse strain, which exhibited no apparent phenotype in both the development and adult stages as compared to wild-type mice.

PPARγ phase separates with RXRα at PPREs to regulate target gene expression.

Peroxisome proliferator-activated receptor (PPAR)-γ is a key transcription activator controlling adipogenesis and lipid metabolism. PPARγ binds PPAR response elements (PPREs) as the obligate heterodimer with retinoid X receptor (RXR) α, but exactly how PPARγ orchestrates the transcriptional response is unknown. This study demonstrates that PPARγ forms phase-separated droplets in vitro and solid-like nuclear condensates in cell, which is intriguingly mediated by its DNA binding domain characterized by the zinc finger motif.

Genetically engineered pH-responsive silk sericin nanospheres with efficient therapeutic effect on ulcerative colitis.

Ulcerative colitis (UC) is one type of inflammatory bowel disease (IBD) and lactoferrin (LF) is a promising protein drug to treat UC. However, targeted LF delivery to optimize bioavailability, targeting and effectiveness remains a challenge. Here, we report an effective strategy to fabricate silk sericin nanospheres systems for the delivery of recombinant human lactoferrin (SS-NS-rhLF).

IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors.

Chimeric antigen receptor (CAR) T cell therapy has been successful in treating hematological malignancy, but solid tumors remain refractory. Here, we demonstrated that knocking out transcription factor IKZF3 in HER2-specific CAR T cells targeting breast cancer cells did not affect CAR expression or CAR T cell differentiation, but markedly enhanced killing of the cancer cells in vitro and in a xenograft model, which was associated with increased T cell activation and proliferation. Furthermore, IKZF3 KO had similar effects on the CD133-specific CAR T cells targeting glioblastoma cells.