Expression of ABC transporters negatively correlates with ectoine biosynthesis in Halomonas campaniensis under NaCl and ultraviolet mutagenesis treatments revealed by transcriptomic and proteomics combined analysis.

Halomonas species are renowned for their production of organic compatible solutes, particularly ectoine. However, the identification of key regulatory genes governing ectoine production in Halomonas remains limited. In this study, we conducted a combined transcriptome-proteome analysis to unveil additional regulatory genes influencing ectoine biosynthesis, particularly under ultraviolet (UV) and salt conditions.

Metabolic engineering of Halomonas campaniensis strain XH26 to remove competing pathways to enhance ectoine production.

Ectoine has gained considerable attention as a high-value chemical with significant application potential and market demand. This study aimed to increase ectoine yields by blocking the metabolic shunt pathway of L-aspartate-4-semialdehyde, the precursor substrate in ectoine synthesis. The homoserine dehydrogenase encoded by hom in H.

Comparative genomic analysis of Halomonas campaniensis wild-type and ultraviolet radiation-mutated strains reveal genomic differences associated with increased ectoine production.

Ectoine is a natural amino acid derivative and one of the most widely used compatible solutes produced by Halomonas species that affects both cellular growth and osmotic equilibrium. The positive effects of UV mutagenesis on both biomass and ectoine content production in ectoine-producing strains have yet to be reported. In this study, the wild-type H.

[Advances in the biomedical application research of halophilic microorganisms].

In recent years, antibiotic resistance has become increasingly serious, and the number of cancer patients keeps increasing. There is an urgent need to develop new drugs with antibacterial and antitumor effects. Halophilic microorganisms are a special group of microorganisms living in extreme environment.

[Advances in the microbial production of the compatible solute ectoine: a review].

Ectoine is an amino acid derivative and an important natural product in halophilic microorganisms. It plays an important role in protecting cells and stabilizing biological macromolecules, and can be widely used in biomedical fields such as drug preparation adjuvants, organ transplantation and preservation, skin wound repair and cosmetics. Due to the medical value and commercial market demand of ectoine, this article summarized the recent advances in the microbial production of ectoine, including the mutation and breeding of hyper-producing strains, construction of genetically and metabolically engineered strains, optimization of fermentation processes, and extraction and purification processes.

Whole genome sequencing of the halophilic Halomonas qaidamensis XH36, a novel species strain with high ectoine production.

Here, we report the whole genome of a novel halophilic Halomonas species strain XH36 with high ectoine production potential. The genome was 3,818,310 bp in size with a GC content of 51.97%, and contained 3533 genes, 61 tRNAs and 18 rRNAs.

Reproducibility and robustness of high-throughput S1500+ transcriptomics on primary rat hepatocytes for chemical-induced hepatotoxicity assessment.

Cell-based models coupled with high-throughput transcriptomics (HTTr) are increasingly utilized as alternative methods to animal-based toxicity testing. Here, using a panel of 14 chemicals with different risks of human drug-induced liver injury (DILI) and two dosing concentrations, we evaluated an HTTr platform comprised of collagen sandwich primary rat hepatocyte culture and the TempO-Seq surrogate S1500+ (ST) assay. First, the HTTr platform was found to exhibit high reproducibility between technical and biological replicates (r greater than 0.

Distinctive distributions of halophilic Archaea across hypersaline environments within the Qaidam Basin of China.

Halophilic Archaea are widely distributed globally in hypersaline environments. However, little is known of how dominant halophilic archaeal genera are distributed across environments and how they may co-associate across ecosystems. Here, the archaeal community composition and diversity from hypersaline environments (> 300 g/L salinity; total of 33 samples) in the Qaidam Basin of China were investigated using high-throughput Illumina sequencing of 16S rRNA genes.

Robust 2D Otsu's Algorithm for Uneven Illumination Image Segmentation.

Otsu's algorithm is one of the most well-known methods for automatic image thresholding. 2D Otsu's method is more robust compared to 1D Otsu's method. However, it still has limitations on salt-and-pepper noise corrupted images and uneven illumination images.

Bacterial and Archaeal Communities within an Ultraoligotrophic, High-altitude Lake in the Pre-Himalayas of the Qinghai-Tibet Plateau.

Puma Yumco Lake (PYL) is an ultraoligotrophic freshwater lake that sits an altitude of 5030 m within the Qinghai-Tibet Plateau of China. The bacterial and archaeal diversity of the lake remains poorly understood, despite their potential to inform on biogeochemical cycling and environment-microbial associations in these unique environments. Here, the bacterial and archaeal communities of PYL were investigated using high-throughput sequencing analysis of community 16S rRNA gene sequences.

An evaluation of the core bacterial communities associated with hypersaline environments in the Qaidam Basin, China.

Hypersaline lakes and saltern areas are important industrial and biodiversity resources in the Qaidam Basin of China that reside at > 2600 m asl. Most hypersaline environments in this area are characterized by saturated salinity (~ 300 g/L salinity), nearly neutral pH, intense ultraviolet radiation, and extremely variable temperature fluctuations. The core bacterial communities associated with these stressful environments have nevertheless remained uninvestigated.

Tethered primary hepatocyte spheroids on polystyrene multi-well plates for high-throughput drug safety testing.

Hepatocyte spheroids are useful models for mimicking liver phenotypes in vitro because of their three-dimensionality. However, the lack of a biomaterial platform which allows the facile manipulation of spheroid cultures on a large scale severely limits their application in automated high-throughput drug safety testing. In addition, there is not yet a robust way of controlling spheroid size, homogeneity and integrity during extended culture.

The effect of temperature fluctuation on the microbial diversity and community structure of rural household biogas digesters at Qinghai Plateau.

Seasonal temperature-fluctuation has been regarded as a key environmental factor affecting rural biogas fermentation yields. The present study investigated the impact of seasonal temperature-fluctuation on operating-temperatures and biogas production in rural household digesters at Qinghai Plateau and revealed the related changes in microbial diversity and community structure by 16S rRNA gene high-throughput sequencing (HTS) analysis. Our results showed closely positive correlation between operating-temperatures and biogas production.

Evaluating Nanoparticles in Preclinical Research Using Microfluidic Systems.

Nanoparticles (NPs) have found a wide range of applications in clinical therapeutic and diagnostic fields. However, currently most NPs are still in the preclinical evaluation phase with few approved for clinical use. Microfluidic systems can simulate dynamic fluid flows, chemical gradients, partitioning of multi-organs as well as local microenvironment controls, offering an efficient and cost-effective opportunity to fast screen NPs in physiologically relevant conditions.

Generation of mature kupffer cells from human induced pluripotent stem cells.

Liver macrophages, Kupffer cells (KCs), play a critical role in drug-induced liver injury (DILI) and liver diseases including cholestasis, liver fibrosis and viral hepatitis. Application of KCs in in vitro models of DILI and liver diseases is hindered due to limited source of human KCs. In vivo, KCs originate from MYB-independent macrophage progenitors, which differentiate into liver-specific macrophages in response to hepatic cues in the liver.

Deep learning enables automated scoring of liver fibrosis stages.

Current liver fibrosis scoring by computer-assisted image analytics is not fully automated as it requires manual preprocessing (segmentation and feature extraction) typically based on domain knowledge in liver pathology. Deep learning-based algorithms can potentially classify these images without the need for preprocessing through learning from a large dataset of images. We investigated the performance of classification models built using a deep learning-based algorithm pre-trained using multiple sources of images to score liver fibrosis and compared them against conventional non-deep learning-based algorithms - artificial neural networks (ANN), multinomial logistic regression (MLR), support vector machines (SVM) and random forests (RF).

In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening.

Exposure to teratogenic chemicals during pregnancy may cause severe birth defects. Due to high inter-species variation of drug responses as well as financial and ethical burdens, despite the widely use of in vivo animal tests, it's crucial to develop highly predictive human pluripotent stem cell (hPSC)-based in vitro assays to identify potential teratogens. Previously we have shown that the morphological disruption of mesoendoderm patterns formed by geometrically-confined cell differentiation and migration using hPSCs could potentially serve as a sensitive morphological marker in teratogen detection.

Mechanosensing in liver regeneration.

Liver is highly regenerative as it can restore its function and size even after 70% partial hepatectomy. During liver regeneration, the mechanical and chemical environment of liver is altered with accumulation of various growth factors and remodeling of extracellular environment. Cells can sense the changes in their cellular environment through various chemo and mechanosensors present on their surfaces.

Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity.

Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied.

A method for human teratogen detection by geometrically confined cell differentiation and migration.

Unintended exposure to teratogenic compounds can lead to various birth defects; however current animal-based testing is limited by time, cost and high inter-species variability. Here, we developed a human-relevant in vitro model, which recapitulated two cellular events characteristic of embryogenesis, to identify potentially teratogenic compounds. We spatially directed mesoendoderm differentiation, epithelial-mesenchymal transition and the ensuing cell migration in micropatterned human pluripotent stem cell (hPSC) colonies to collectively form an annular mesoendoderm pattern.

Modulation of integrin and E-cadherin-mediated adhesions to spatially control heterogeneity in human pluripotent stem cell differentiation.

Heterogeneity in human pluripotent stem cell (PSC) fates is partially caused by mechanical asymmetry arising from spatial polarization of cell-cell and cell-matrix adhesions. Independent studies have shown that integrin and E-cadherin adhesions promote opposing differentiation and pluripotent fates respectively although their crosstalk mechanism in modulating cell fate heterogeneity remains unknown. Here, we demonstrated that spatial polarization of integrin and E-cadherin adhesions in a human PSC colony compete to recruit Rho-ROCK activated myosin II to different localities to pattern pluripotent-differentiation decisions, resulting in spatially heterogeneous colonies.

Simultaneous quantification of chrysophanol and physcion in rat plasma by ultra fast liquid chromatography-tandem mass spectrometry and application of the technique to comparative pharmacokinetic studies of Radix et Rhei Rhizoma extract alone and Dahuang Fuzi Decoction.

Most herbal medicines are prescribed in combination based on the theory of TCM to obtain synergistic effects or diminish the possible adverse reactions. Compatibility refers to the combination of two or more herbs based on the clinical settings and the properties of herbs. Chrysophanol and physcion are the main effective compounds in Radix et Rhizoma Rhei and Dahuang Fuzi Decoction which is the combination of Radix et Rhizoma Rhei, Radix Aconiti Lateralis Praeparata and Radix et Rhizoma Asari.