Biodegradation of phthalate acid esters and whole-genome analysis of a novel Streptomyces sp. FZ201 isolated from natural habitats.

Di-n-butyl phthalate (DBP) is one of the most extensively used phthalic acid esters (PAEs) and is considered to be an emerging, globally concerning pollutant. The genus Streptomyces holds promise as a degrader of various organic pollutants, but PAE biodegradation mechanisms by Streptomyces species remain unsolved. In this study, a novel PAE-degrading Streptomyces sp. FZ201 isolated from natural habitats efficiently degraded various PAEs. FZ201 had strong resilience against DBP and exhibited immediate degradation, with kinetics adhering to a first-order model. The comprehensive biodegradation of DBP involves de-esterification, ß-oxidation, trans-esterification, and aromatic ring cleavage. FZ201 contains numerous catabolic genes that potentially facilitate PAE biodegradation. The DBP metabolic pathway was reconstructed by genome annotation and intermediate identification. Streptomyces species have an open pangenome with substantial genome expansion events during the evolutionary process, enabling extensive genetic diversity and highly plastic genomes within the Streptomyces genus. FZ201 had a diverse array of highly expressed genes associated with the degradation of PAEs, potentially contributing significantly to its adaptive advantage and efficiency of PAE degradation. Thus, FZ201 is a promising candidate for remediating highly PAE-contaminated environments. These findings enhance our preliminary understanding of the molecular mechanisms employed by Streptomyces for the removal of PAEs.

The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury.

AIM: To investigate the effect of the gp130/STAT3-endoplasmic reticulum (ER) stress axis on hepatocyte necroptosis during acute liver injury. METHODS: ER stress and liver injury in LO2 cells were induced with thapsigargin, and in BALB/c mice with tunicamycin and carbon tetrachloride (CCl4). Glycoprotein 130 (gp130) expression, the degrees of ER stress, and hepatocyte necroptosis were assessed. RESULTS: ER stress significantly upregulated gp130 expression in LO2 cells and mouse livers. The silencing of activating transcription factor 6 (ATF6), but not of ATF4, increased hepatocyte necroptosis and mitigated gp130 expression in LO2 cells and mice. Gp130 silencing reduced the phosphorylation of CCl4-induced signal transducer and activator of transcription 3 (STAT3), and aggravated ER stress, necroptosis, and liver injury in mice. CONCLUSION: ATF6/gp130/STAT3 signaling attenuates necroptosis in hepatocytes through the negative regulation of ER stress during liver injury. Hepatocyte ATF6/gp130/STAT3 signaling may be used as a therapeutic target in acute liver injury.

Relationship of familial cytochrome P450 4V2 gene mutation with liver cirrhosis: A case report and review of the literature.

BACKGROUND: Many genetic and metabolic diseases affect the liver, but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns. There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods. CASE SUMMARY: We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema, abdominal distension, cirrhosis, and hypothyroidism. We excluded the common causes of liver disease (drinking alcohol, using traditional Chinese medicines, hepatitis virus infection, autoimmunity, and hepatolenticular degeneration). When she was 23-years-old, she developed night-blindness that worsened to complete blindness, with no obvious cause. Her parents were first cousins, and both were alive. Analysis of the patient's family history indicated that all 5 siblings had night blindness and impaired vision; one sister was completely blind; and another sister had night-blindness complicated with cirrhosis and subclinical hypothyroidism. Entire exome sequencing showed that the patient, parents, and siblings all had mutations in the cytochrome P450 4V2 gene (CYP4V2). The CYP4V2 mutations of the parents and two sisters were heterozygous, and the others were homozygous. Two siblings also had heterozygous dual oxidase activator 2 (DUOXA2) mutations. CONCLUSION: Mutations in the CYP4V2 gene may affect lipid metabolism and lead to chronic liver injury, fibrosis, and cirrhosis.

Feedback loop between hepatocyte nuclear factor 1α and endoplasmic reticulum stress mitigates liver injury by downregulating hepatocyte apoptosis.

Hepatocyte nuclear factor alpha (HNF1α), endoplasmic reticulum (ER) stress, and hepatocyte apoptosis contribute to severe acute exacerbation (SAE) of liver injury. Here, we explore HNF1α-ER stress-hepatocyte apoptosis interaction in liver injury. LO2, HepG2 and SK-Hep1 cells were treated with thapsigargin (TG) or tunicamycin (TM) to induce ER stress. Carbon tetrachloride (CCl4) was used to induce acute liver injury in mice. Low-dose lipopolysaccharide (LPS) exacerbated liver injury in CCl4-induced mice. Significant apoptosis, HNF1α upregulation, and nuclear factor kappa B (NF-κB) activation were observed in human-derived hepatocytes during ER stress. Knockdown of Rela, NF-κB p65, inhibited the HNF1α upregulation. Following CCl4 treatment ER stress, apoptosis, HNF1α expression and RelA phosphorylation were significantly increased in mice. HNF1α knockdown reduced activating transcription factor 4 (ATF4) expression, and aggravated ER stress as well as hepatocyte apoptosis in vivo and in vitro. The double fluorescent reporter gene assay confirmed that HNF1α regulated the transcription of ATF4 promoter. LPS aggravated CCl4-induced liver injury and reduced HNF1α, and ATF4 expression. Therefore, in combination, HNF1α and ER stress could be mutually regulated forming a feedback loop, which helps in protecting the injured liver by down-regulating hepatocyte apoptosis. Low-dose LPS aggravates hepatocyte apoptosis and promotes the SAE of liver injury by interfering with the feedback regulation of HNF1α and ER stress in acute liver injury.

Transcriptome and Metabonomics Analysis Revealed the Molecular Mechanism of Differential Metabolite Production of Dendrobium nobile Under Different Epiphytic Patterns.

The cultivation medium of Dendrobium nobile has an effect on the contents of its main medicinal components, but the specific mechanism is still unclear. In this study, the callus, seedlings, rhizomes, and leaves of D. nobile were sequenced for the PacBio SMRT. The 2-year-old stems were selected for the Illumina sequencing and metabolome sequencing to analyze the genetic mechanism of metabolic differences under different epiphytic patterns. As a result, a total of 387 differential genes were obtained, corresponding to 66 differential metabolites. Different epiphytic patterns can induce a series of metabolic changes at the metabolome and transcriptome levels of D. nobile, including flavonoid metabolism, purine metabolism, terpenoid backbone biosynthesis, amino acid metabolism, and alpha-linolenic acid metabolic, and related regulatory genes include ALDH2B7, ADC, EPSPS-1, SHKA, DHAPS-1, GES, ACS1, SAHH, ACS2, CHLP, LOX2, LOX2.3, and CYP74B2. The results showed that the genetic mechanism of D. nobile under various epiphytic patterns was different. In theory, the content of metabolites under the epiphytic patterns of Danxia stone is higher, which is more suitable for field cultivation.

Mechanisms by Which Traditional Chinese Medicines Influence the Intestinal Flora and Intestinal Barrier.

The effect of a drug on the intestinal flora and the intestinal barrier is an important evaluation index for drug safety and efficacy. Chemical synthetic drugs are widely used due to their advantages of fast efficacy and low doses, but they are prone to cause drug resistance and inhibit proton pumps, which may harm intestinal health. Traditional Chinese medicine (TCM) has been applied clinically for thousands of years, and how TCMs regulate intestinal health to achieve their effects of disease treatment has become a hot research topic that needs to be resolved. This paper reviews the recent research on the effects of TCMs on intestinal microorganisms and the intestinal mucosal barrier after entering the intestine, discusses the interaction mechanisms between TCMs and intestinal flora, and details the repair effect of TCMs on the intestinal mucosal barrier to provide a reference for the development, utilization, and modernization of TCM.

Glucosyloxybenzyl 2-isobutylmalates and phenolic glycosides from the flowers of Bletilla striata.

Four previously undescribed compounds, including three glucosyloxybenzyl 2-isobutylmalates (1-3), one phenolic glycoside (4), along with ten known compounds were isolated from the flowers of Bletilla striata. The structures and absolute configurations of the undescribed compounds were elucidated on the basis of HR-ESIMS, NMR spectroscopy, optical rotation value, and acid hydrolysis experiment. Cytotoxicity of the isolated compounds against A549, HCT-116, and SW1990 cells and protective effects of t-BHP-induced L02 cytotoxic were assayed. The antioxidant activities of the isolated compounds were also evaluated.

Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model.

BACKGROUND: Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. METHODS: In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. RESULTS: TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression (p < 0.05) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress (p < 0.05). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers (p < 0.05). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. CONCLUSIONS: Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

Chemical constituents of Bletilla striata.

A new triphenanthrene compound named 2,2',2'',7,7',7''-hexahydroxy-4,4',4''-trimethoxy-[9,9',9'',10,10',10'']-hexahydro-1,8,1',6''-triphenanthrene (1), together with eleven known compounds (2－12), were isolated from tubers of Bletilla striata. Their structures were determined by analysis of spectroscopic data.

Three new 1-(p-hydroxybenzyl)phenanthrenes from Bletilla striata.

Three new benzylphenanthrenes, named 1-(p-hydroxybenzyl)-4,7-dimethoxyphenanthrene-2-ol (1), 1-(p-hydroxybenzyl)-4,7-dimethoxyphenanthrene-2,8-diol (2), and 1-(p-hydroxybenzyl)-4,7-dimethoxyphenanthrene-2,6-diol (3), along with a known analog were isolated from tubers of Bletilla striata. The structures of these new compounds were established by means of HR-ESI-MS, 1D, and 2D NMR.

[Microbial biomass and its correlations with carbon, nitrogen, and phosphorus in the sediments of Taihu Lake].

To explore the responses and feedbacks of the microbes in the sediments of Taihu Lake to the sediment nutrients, an investigation was made on the microbial biomass carbon (MB(C)), microbial biomass nitrogen (MB(N)), microbial biomass phosphorus (MB(P)), and their correlations with the total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) in the sediments. The microbial biomass in the sediments was 184.66 mg x kg(-1), being higher at the lakeside than in the mid-lake region. The MB(C) was higher in the western coastal region, Zhushan Bay, and Meiliang Bay, with an average of 127.57 mg x kg(-1), MB(N) was higher in Meiliang Bay, Gonghu Bay, mid-lake region close to Meiliang Bay and Gonghu Bay, and eastern costal region, with an average of 19.25 mg x kg(-1), and MB(P) was higher in the eastern region and parts of the mid-lake region, with an average was 19.09 mg x kg(-1). The TOC high value zone (> or = 2.30 g x kg(-1)) was mainly in Zhushan Bay, western coastal region, Meiliang Bay, and Gonghu Bay, with an average of 1.59 g x kg(-1), TN high value zone (> or = 0.30 g x kg(-1)) was mainly in the Gonghu Bay, Meiliang Bay, Zhushan Bay, and western costal region, with an average of 0.21 g x kg(-1), and TP high value zone (> or = 1.20 g x kg(-1)) was mainly in the eastern coastal region and parts of the mid-lake region, with an average of 0.55 g x kg(-1). The TOC/TN ratio in the sediments was 7-19, with an average of 8.97, which showed that the organic substances in the sediments had obvious dual sources, among which, terrestrial organisms were mainly in the west side of the lake. The microbial biomass in the sediments was significantly positively correlated with sediment TOC and TN but had less correlation with sediment TP, and the MB(C)/MB(N) was significantly correlated with sediment TOC/TN, suggesting that the microbes in the sediments of Taihu Lake were mainly affected by the sediment TOC and TN, and the changes of the TOC/TN had significant effects on the microbial community structure.

De novo assembly and characterization of the root transcriptome of Aegilops variabilis during an interaction with the cereal cyst nematode.

BACKGROUND: Aegilops variabilis No.1 is highly resistant to cereal cyst nematode (CCN). However, a lack of genomic information has restricted studies on CCN resistance genes in Ae. variabilis and has limited genetic applications in wheat breeding. RESULTS: Using RNA-Seq technology, we generated a root transcriptome at a sequencing depth of 4.69 gigabases of Ae. variabilis No. 1 from a pooled RNA sample. The sample contained equal amounts of RNA extracted from CCN-infected and untreated control plants at three time-points. Using the Trinity method, nearly 52,081,238 high-quality trimmed reads were assembled into a non-redundant set of 118,064 unigenes with an average length of 500 bp and an N50 of 599 bp. The total assembly was 59.09 Mb of unique transcriptome sequences with average read-depth coverage of 33.25×. In BLAST searches of our database against public databases, 66.46% (78,467) of the unigenes were annotated with gene descriptions, conserved protein domains, or gene ontology terms. Functional categorization further revealed 7,408 individual unigenes and three pathways related to plant stress resistance. CONCLUSIONS: We conducted high-resolution transcriptome profiling related to root development and the response to CCN infection in Ae. variabilis No.1. This research facilitates further studies on gene discovery and on the molecular mechanisms related to CCN resistance.