Intelligent bacterial platform induces programmed death-ligand 1 lysosomal degradation to enhance antitumor immunity.

Engineered bacteria have emerged as a promising therapeutic strategy for tumor therapy by exploiting the unique features of the tumor microenvironment (TME). In this study, we developed a low-endotoxin Escherichia coli expression system to produce a fusion protein comprising the CXCL12 with the nanobody KN035 Hypoxia and immunosuppression drive the selective colonization of engineered bacteria in tumor tissues, minimizing host toxicity. Unlike conventional PD-L1 antibodies that merely block immune checkpoints, our CXCL12-KN035 fusion protein simultaneously targets the CXCR7 receptor and PD-L1 on tumor cells, inducing receptor internalization and subsequent lysosomal degradation of PD-L1.

[Laser-assisted spatiotemporal control of Noxa expression in engineering bacteria for treating tumors].

Bacterial therapy has attracted increasing attention due to its special mechanism and abundant applications. With the flourishing development of synthetic biology, therapeutic genes have been introduced into engineering bacteria to improve their antitumor efficacy. However, it is difficult to spatiotemporally control the expression of these therapeutic genes at the tumor site , thereby considerably limiting the application of engineered bacteria in tumor treatment.

Modulation of hepatic immune-metabolic pathways by oligochitosan in hybrid grouper infected with Edwardsiella ictaluri.

Edwardsiella ictaluri, an important pathogen in aquaculture, can cause severe liver damage and metabolic disorders in fish. In this study, we investigated the effect of dietary oligochitosan on hybrid grouper infected with E. ictaluri.

Cardiomyocyte-specific LARP6 overexpression prevents angiotensin II-induced myocardial dysfunction and interstitial fibrosis.

La ribonucleoprotein 6, Translational Regulator (LARP6), a multifunctional mRNA binding protein with well-described pro-fibrotic effects, increases type I collagen mRNA half-life, translation, and deposition in non-cardiac tissues. In the heart LARP6 is expressed in cardiomyocytes, not primarily involved in fibrosis, where its role is unknown. To investigate the role of cardiomyocyte-derived LARP6 on cardiac function and remodeling, we generated a cardiomyocyte-specific LARP6 overexpressing transgenic mouse model (LARP6-Tg).

Captopril alleviates radiation-induced pulmonary fibrosis by suppressing PAI-1 expression and cytoskeleton-dependent epithelial-to-mesenchymal transition.

Radiation-induced lung injury (RILI) remains a significant complication of thoracic radiotherapy, with radiation-induced pulmonary fibrosis (RIPF) representing a serious and irreversible outcome. Epithelial-mesenchymal transition (EMT) has emerged as a critical contributor to RIPF progression; however, the underlying mechanisms remain poorly understood. Captopril (Cap), an angiotensin-converting enzyme inhibitor with established cardiovascular benefits, has been demonstrated to show protective effects against RILI.

Expression of concern: The effect of metal ions on endogenous melanin nanoparticles used as magnetic resonance imaging contrast agents.

Expression of Concern for 'The effect of metal ions on endogenous melanin nanoparticles used as magnetic resonance imaging contrast agents' by Anqi Chen , , 2020, , 379-390, https://doi.org/10.1039/C9BM01580A.

Subfunctionalization, neofunctionalization, and nonfunctionalization of the four soybean phytochrome A genes.

Gene duplication generates new genes, which retain their original function or undergo subfunctionalization, neofunctionalization, or nonfunctionalization. The phytochrome A (PHYA) genes in soybean (Glycine max) have undergone duplication to produce GmPHYA1, GmPHYA2 (E4), GmPHYA3 (E3), and GmPHYA4, each with distinct evolutionary fates. Using genetic and biochemical analyses, we discovered that GmPHYA1 has undergone subfunctionalization and is essential for regulating photomorphogenesis and plant height in soybean.

Engineered Probiotic Hydrogel Alleviates Vaginitis via Antimicrobial and Anti-inflammatory Pathways.

Vulvovaginal candidiasis (VVC), primarily caused by , is a prevalent infection that presents significant clinical challenges. Current antifungal treatments have limitations, including a narrow antimicrobial spectrum and a lack of anti-inflammatory effects. To address these limitations, we genetically modified to produce high-molecular-weight hyaluronic acid (HMHA) for sustained local delivery of antimicrobial peptides (AMP) and HMHA at the infection site.

Characterizing Duodenal Immune Microenvironment in Functional Dyspepsia: An AutoML-Driven Diagnostic Framework.

Background: Functional dyspepsia (FD) is a prevalent gastroduodenal disorder with an unclear pathogenesis. Recent studies suggest that duodenal immune activation plays a pivotal role in its development.

Methods: Mendelian randomization analysis using genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data identified genes associated with FD.

A dual-tag strategy with superfolder green fluorescent protein (sfGFP) and small ubiquitin-like modifier (SUMO) for soluble expression of SARS-CoV-2 RNA polymerase visibly in Escherichia coli.

RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 composed of three non-structural proteins NSP12, NSP8, and NSP7, which is responsible for replication and transcription, making it a promising target for antiviral drug development. However, the limited solubility presents a significant challenge in the expression of NSP12, restricting in-depth research in both scientific and clinical fields. To address the challenge of soluble expression of NSP12 using the bacterial expression system, we developed a strategy integrating the super-folder GFP (sfGFP) tag to overcome the low solubility of NSP12 in this study.

Efficient radical generator with NIR emission by donor modulation for mitochondria-targeted photodynamic therapy.

Development of NIR type I photosensitizers (PSs) that can specifically target subcellular organelles remains a significant challenge in photodynamic therapy (PDT). In this work, two D-π-A PSs named TPE-IN and TPA-IN were constructed via the strategy of changing donors. In detail, replacing donor group tetraphenylethylene (TPE-IN) with triphenylamine (TPA-IN) could extend the emission wavelength of PSs into the NIR-I region.

Recent Developments and Applications of Surface-Enhanced Raman Scattering Spectroscopy in Pesticides Detection: From Single Pesticides to Mixed Pesticides.

Pesticides directly pollute the environment and food, eventually being absorbed into the human body. Their residues are highly toxic and pose serious health risks. Chromatography and gas liquid chromatography tandem mass spectrometry are widely employed for pesticide residue detection.

Improving the Catalytic Activity and Thermostability of FAST-PETase with a Multifunctional Short Peptide.

Previous reports indicated that self-assembling amphipathic peptide S1v1 (AEAEAHAH) significantly enhances the soluble expression, thermostability, and activity of the target proteins when fused to them. In order to obtain high-efficiency enzymes for the large-scale degradation of polyethylene terephthalate (PET), this multifunctional peptide was fused to the N- and C-terminus of FAST-PETase, a variant of PETase (PETase), with a PT-linker (TTVTTPQTS) harbored between the target protein and the multifunctional peptide. Consistent with previous reports, S1v1 increased the solubility of FAST-PETase slightly.

Establishing a Novel Heterologous Secretion Expression System Mediated by mScarlet3 for the Expression of a Novel Lipolytic Enzyme.

Our previous study demonstrated that an heterologous secretion expression system, mediated by superfolder green fluorescent protein (sfGFP) mutants, significantly enhances recombinant lipase yield and reduces large-scale production costs. In this study, we identified mScarlet3, a fast-folding fluorescent protein, as another effective mediator of secretion expression in . A novel lipolytic enzyme, named LipHu6, was identified through sequence alignment.

In vitro programmable DNA cleavage by a eukaryotic Argonaute.

Eukaryotic Argonautes (eAgos) have traditionally been characterized by their ability to utilize RNA guides to identify RNA targets, thereby engaging in post-transcriptional gene silencing pathways. While some eAgos have been demonstrated to use DNA guides for RNA cleavage, the ability of eAgos to cleave DNA targets remains unclear. In this study, we characterized CsAgo, an eAgo protein derived from thermophilic eukaryote Chaetomiumsp.

Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels.

The main obstacles to the clinical application of the CRISPR/Cas9 system are off-target effects and low delivery efficiency. There is an urgent need to develop new delivery strategies and technologies. Three types of in situ injectable hydrogels with different electrical properties were created to find the most secure and efficient sustained-release drug delivery system.

Minibinders targeting Staphylococcus aureus α-toxin exert protective effects in vivo.

Staphylococcus aureus is a leading bacterial pathogen worldwide. It secrets α-toxin, a pore-forming cytotoxin that significantly contributes to the pathogenesis of pneumonia, skin necrosis, and lethal infections. Targeting α-toxin has emerged as a promising strategy for developing therapeutics against S.

Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population.

Background And Purpose: Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.

An Engineered PfAgo with Wide Catalytic Temperature Range and Substrate Spectrum.

PfAgo, a thermophilic Argonaute nuclease from Pyrococcus furiosus, is widely used in various fields due to its high DNA-guided DNA cleavage activity. However, its high-temperature-dependent cleavage activity largely restricts its applications in moderate-temperature scenarios. In this study, PfAgo is engineered for cold adaptation based on its ternary complex structure and the attributes of cold-adapted enzymes, yielding a series of variants with better performance at moderate temperatures.

Argonaute-driven programmable multi-enzyme complex assembly on ribosomal RNA scaffolds.

Scaffold-based multi-enzyme assembly strategies have significantly advanced biocatalysis by enhancing reaction efficiency through precise spatial organization of enzymes. While DNA- and protein-based scaffolds have been extensively studied, RNA scaffolds present unique advantages, including structural flexibility, dynamic regulation, and functional diversity. However, their application in vitro has been limited due to challenges related to stability and cost.

Synergistic Treatment with Ozone Water and Morpholine Fatty Acid Salts Improves Postharvest Quality in Mandarin Oranges.

Citrus rot seriously reduces the quality of citrus, causes economic losses, and is an urgent problem for the citrus industry. Effective preservation and pretreatment methods have an important impact on the maintenance of mandarin orange quality. In this study, mandarin orange was pretreated through single and synergistic treatments with ozone water and morpholine fatty acid salts in order to assess their effects on the fruit's physicochemical properties.

The Effect of Gliding Arc Discharge Low-Temperature Plasma Pretreatment on Blueberry Drying.

This study evaluates the effects of gliding arc discharge low-temperature plasma (GAD-LTP) pretreatment on the drying performance and quality attributes of blueberries. Fresh blueberries were pretreated under varying conditions-treatment durations of 6 s, 12 s, and 18 s and power levels of 300 W, 600 W, and 900 W-prior to convective hot air drying at 65 °C. Results demonstrate that plasma pretreatment significantly reduced drying time, with an 18 s treatment at 900 W reducing drying time by 31.

Catalytic hairpin assembly assists CRISPR/Cas12a-mediated high-sensitivity detection of aflatoxin B1.

Aflatoxin B1 (AFB1) is recognized the most toxic and carcinogenic mycotoxin and is widely present in cereals and various foods. Therefore, its precise detection is crucial to safeguard food quality and human health. In this study, we proposed a highly sensitive detection system for AFB1 by combining the catalytic hairpin assembly (CHA) and CRISPR/Cas12a techniques.

Designed peptide binders and nanobodies as PROTAC starting points for targeted degradation of PCNA and BCL6.

The efficient degradation of pathogenic proteins, particularly proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 6 protein (BCL6), is crucial for treating various diseases related to cancer. As key biological macromolecules, PCNA plays a critical role in DNA replication and repair, while BCL6 acts as a transcriptional repressor involved in B-cell lymphoma. To enhance the efficiency and specificity of protein degradation, we developed a RS80E-based bioPROTACs system that consists of truncated variants of Ring-B-boxed coiled-coil (RBCC) domains (RS80E) with improved degradation efficiency fused to an AI-driven binder/nanobody targeting specific antigens.

Structure-guided engineering of a Rieske-type aromatic dioxygenase for enhanced consumption of 3-phenylpropionic acid in Escherichia coli.

Industrial derived aromatic hydrocarbons are persistent environmental pollutants due to their chemical stability, posing both ecological and health risks. Rieske-type aromatic dioxygenases (RDOs), known for their role in dihydroxylation of aromatic rings, play a pivotal role in microbial consumption and degradation of such compounds. While the industrial application of these enzymes has been impeded by their instability and low biodegradation rate.