Fetal hepatocytes protect the HSPC genome via fetuin-A.

The maintenance of genomic integrity in rapidly proliferating cells is a substantial challenge during embryonic development. Although numerous cell-intrinsic mechanisms have been revealed, little is known about genome-protective effects and influences of developmental tissue microenvironments on tissue-forming cells. Here we show that fetal liver hepatocytes provide protection to haematopoietic stem and progenitor cell (HSPC) genomes.

Engineering Halomonas bluephagenesis for synthesis of polyhydroxybutyrate (PHB) in the presence of high nitrogen containing media.

The trade-offs exist between microbial growth and bioproduct synthesis including intracellular polyester polyhydroxybutyrate (PHB). Under nitrogen limitation, more carbon flux is directed to PHB synthesis while growth is inhibited with diminishing overall carbon utilization, similar to the suboptimal carbon utilization during glycolysis-derived pyruvate decarboxylation. This study reconfigured the central carbon network of Halomonas bluephagenesis to improve PHB yield theoretically and practically.

Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice.

Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice.

Engineered Halomonas for production of gamma-aminobutyric acid and 2-pyrrolidone.

Gamma-Aminobutyric acid (GABA) is a derivative of L-glutamate, also a precursor for the synthesis of 2-pyrrolidone, which is a monomer of nylon-4. This study achieved a one-step biosynthesis of GABA and 2-pyrrolidone by Halomonas bluephagenesis overexpressing key genes involved in GABA and 2-pyrrolidone synthesis and deleting GABA degradation genes combined with reducing the degradation of 2-pyrrolidone precursor. The resulting H.

Metabolically activated energetic materials mediate cellular anabolism for bone regeneration.

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation.

Secreted PTEN binds PLXDC2 on macrophages to drive antitumor immunity and tumor suppression.

Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice.

Trafficking circuit of CD8 T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8CD44CD62L central memory T cells into CD8CD44CD62L T cells, designated as inter-organ migratory T cells (T cells).

A long-term growth stable Halomonas sp. deleted with multiple transposases guided by its metabolic network model Halo-ecGEM.

Microbial instability is a common problem during bio-production based on microbial hosts. Halomonas bluephagenesis has been developed as a chassis for next generation industrial biotechnology (NGIB) under open and unsterile conditions. However, the hidden genomic information and peculiar metabolism have significantly hampered its deep exploitation for cell-factory engineering.

VEGF-induced Nrdp1 deficiency in vascular endothelial cells promotes cancer metastasis by degrading vascular basement membrane.

Vascular endothelial cells (VECs) are key players in the formation of neovessels and tumor metastasis, the ultimate cause of the majority of cancer-related human death. However, the crosstalk between VECs and metastasis remain greatly elusive. Based on our finding that tumor-associated VECs present significant decrease of Nrdp1 protein which is closely correlated with higher metastatic probability, herein we show that the conditional medium from hypoxia-incubated cancer cells induces extensive Nrdp1 downregulation in human and mouse VECs by vascular endothelial growth factor (VEGF), which activates CHIP, followed by Nrdp1 degradation in ubiquitin-proteasome-dependent way.

Potential Benefits of Green Tea in Prostate Cancer Prevention and Treatment: A Comprehensive Review.

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature.

Ectoine hyperproduction by engineered Halomonas bluephagenesis.

Ectoine, a crucial osmoprotectant for salt adaptation in halophiles, has gained growing interest in cosmetics and medical industries. However, its production remains challenged by stringent fermentation process in model microorganisms and low production level in its native producers. Here, we systematically engineered the native ectoine producer Halomonas bluephagenesis for ectoine production by overexpressing ectABC operon, increasing precursors availability, enhancing product transport system and optimizing its growth medium.

Surgical management of nervus intermedius neuralgia: A report of 4 cases and literature review.

Background: Nervus intermedius neuralgia (NIN) is characterized by paroxysmal episodes of sharp, lancinating pain in the deep ear. Unfortunately, only a few studies exist in the literature on this pain syndrome, its pathology and postoperative outcomes.

Method: We conducted a retrospective review of four cases diagnosed with NIN who underwent a neurosurgical intervention at our center from January 2015 to January 2023.

Additive manufacturing of wet-spun chitosan/hyaluronic acid scaffolds for biomedical applications.

Additive manufacturing (AM) holds great potential for processing natural polymer hydrogels into 3D scaffolds exploitable for tissue engineering and in vitro tissue modelling. The aim of this research activity was to assess the suitability of computer-aided wet-spinning (CAWS) for AM of hyaluronic acid (HA)/chitosan (Cs) polyelectrolyte complex (PEC) hydrogels. A post-printing treatment based on HA chemical cross-linking via transesterification with poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was investigated to enhance the structural stability of the developed scaffolds in physiological conditions.

PHA is not just a bioplastic!

Polyhydroxyalkanoates (PHA) have evolved into versatile biopolymers, transcending their origins as mere bioplastics. This extensive review delves into the multifaceted landscape of PHA applications, shedding light on the diverse industries that have harnessed their potential. PHA has proven to be an invaluable eco-conscious option for packaging materials, finding use in films foams, paper coatings and even straws.

Nonsterile microbial production of chemicals based on Halomonas spp.

The use of extremophile organisms such as Halomomas spp. can eliminate the need for fermentation sterilization, significantly reducing process costs. Microbial fermentation is considered a pivotal strategy to reduce reliance on fossil fuel resources; however, sustainable processes continue to incur higher costs than their chemical industry counterparts.

Flux optimization using multiple promoters in Halomonas bluephagenesis as a model chassis of the next generation industrial biotechnology.

Predictability and robustness are challenges for bioproduction because of the unstable intracellular synthetic activities. With the deeper understanding of the gene expression process, fine-tuning has become a meaningful tool for biosynthesis optimization. This study characterized several gene expression elements and constructed a multiple inducible system that responds to ten different small chemical inducers in halophile bacterium Halomonas bluephagenesis.

Construction of a Stable Expression System Based on the Endogenous / Toxin-Antitoxin System of .

is a halophilic bacterium capable of efficiently producing polyhydroxyalkanoates and other valuable chemicals through high salinity open fermentation, offering an appealing platform for next-generation industrial biotechnology. Various techniques have been developed to engineer , each with its inherent shortcomings. Genome editing methods often entail complex and time-consuming processes, while flexible expression systems relying on plasmids necessitate the use of antibiotics.

Metabolic engineering of Halomonas bluephagenesis for production of five carbon molecular chemicals derived from L-lysine.

5-Aminovaleric acid (5-AVA), 5-hydroxyvalerate (5HV), copolymer P(3HB-co-5HV) of 3-hydroxybutyrate (3HB) and 5HV were produced from L-lysine as a substrate by recombinant Halomonas bluephagenesis constructed based on codon optimization, deletions of competitive pathway and L-lysine export protein, and three copies of davBA genes encoding L-lysine monooxygenase (DavB) and 5-aminovaleramide amidohydrolase (DavA) inserted into its genome to form H. bluephagenesis YF117ΔgabT, which produced 16.4 g L and 67.

Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction.

An overwhelming number of studies have reported the correlation of decreased abundance of butyrate-producing commensals with a wide range of diseases. However, the molecular-level mechanisms whereby gut butyrate causally affects the host mucosal immunity and pathogenesis were poorly understood, hindered by the lack of efficient tools to control intestinal butyrate. Here we engineered a facultative anaerobic commensal bacterium to delivery butyrate at the intestinal mucosal surface, and implemented it to dissect the causal role of gut butyrate in regulating host intestinal homeostasis in a model of murine chronic colitis.

Engineering low-salt growth Halomonas Bluephagenesis for cost-effective bioproduction combined with adaptive evolution.

Halophilic Halomonas bluephagenesis has been engineered to produce various added-value bio-compounds with reduced costs. However, the salt-stress regulatory mechanism remained unclear. H.

Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis.

Background: Despite increasing evidence that has shown the association of ultra-processed foods (UPFs) with cancer risk, the results remain inconclusive. We, therefore, conducted the meta-analysis to clarify the association by including recently published studies.

Methods: A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies from inception to January 2023.

Simultaneous profiling of host expression and microbial abundance by spatial metatranscriptome sequencing.

We developed an analysis pipeline that can extract microbial sequences from spatial transcriptomic (ST) data and assign taxonomic labels, generating a spatial microbial abundance matrix in addition to the default host expression matrix, enabling simultaneous analysis of host expression and microbial distribution. We called the pipeline spatial metatranscriptome (SMT) and applied it on both human and murine intestinal sections and validated the spatial microbial abundance information with alternative assays. Biological insights were gained from these novel data that showed host-microbe interaction at various spatial scales.

3-Hydroxybutyrate ameliorates insulin resistance by inhibiting PPARγ Ser273 phosphorylation in type 2 diabetic mice.

3-Hydroxybutyrate (3HB) is a small ketone body molecule produced endogenously by the body in the liver. Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic (T2D) patients. However, there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of 3HB.