Small mother against decapentaplegic (SMAD) family member 3 (SMAD3) is well correlated with the inflammatory response of chronic obstructive pulmonary disease (COPD). A previous study indicated that the single nucleotide polymorphism (SNP) rs36221701 of SMAD3 was related to the risk of inflammatory disease. Hence, given the pathogenesis of COPD is intently associated with smoking and gene polymorphism, this study aims to analyze the relationship between SMAD3 rs36221701 and COPD susceptibility, and to explore whether the interaction is related to smoking status. We studied the association between the rs36221701 and rs34307601 of SMAD3 and COPD susceptibility, a total of 541 COPD patients and 534 controls of the Uyghur population were recruited at the First People's Hospital and the village of Kashi. The interrelation of the two SNPs with the risk of COPD was determined by calculating odds ratio (OR) and 95% confidence interval (95% CI). We found a significant association between the rs36221701 and COPD risk in the non-smoking population. TC genotype showed a significant decreased association with COPD risk (OR = 0.59, 95% CI = 0.41-0.83, P < 0.05), but CC genotype can increased the COPD risk (OR > 1, P < 0.05). In addition, COPD susceptibility was not related to the genetic variations in the rs34307601 (P > 0.05). In conclusion, we confirmed that the SMAD3 rs36221701 may be associated with COPD susceptibility in the Chinese Uyghur population, especially among non-smokers. Our data provide new light for the relationship between SMAD3 gene polymorphisms and COPD susceptibility in the Chinese Uyghur population.

Gastric cancer (GC)-derived cell lines were generally used in basic cancer research and drug screening. However, it is always concerned about the difference between cultured cells and primary tumor by oncologists. To address this question, we compared differentially expressed genes (DEGs) in primary cancers, healthy tissues, and cell lines both in vitro and in silico. Seven reported genes with decreased expression in GCs by DNA methylation were analyzed in our cohort studies and experimentally validation. Selected datasets from TCGA (The Cancer Genome Atlas), CCLE (The Broad Institute Cancer Cell Line Encyclopedia), and GTEx (The Genotype-Tissue Expression project) were used to represent GCs, GC-derived cell lines, and healthy tissues respectively in the in silico analysis. Thirty gastric tissues together with six cell lines were used for validations. Unexpectedly, we experimentally found that reported cancer-related downregulated genes were only found in cancer cell lines but not in biopsies. The unchanged gene expressions in primary GCs were generally consistent with our cohort study, using information from cancerous (TCGA) and healthy tissues (GETx). Substantial differences were also found between DEGs of cancer tissues (TGCA)/ healthy tissues (GTEx) pair and cell lines (CCLE)/ healthy tissues (GTEx) pair, which confirmed the significant differences between primary cancer and cancer cell lines. Moreover, elevated expression of YWHAQ (14-3-3 δ) and THBS1 were observed in the GC biopsies, which might be potential biomarkers for GC diagnosis, considering the increased YWHAQ and THBS1 associated with poor survival rates in gastric cancer patients. In sum, it is suggested that cautions should be taken when using GC cell lines to study genes that show great differences between cell lines and tissues.

In this study, a method for the rapid screening, expression and purification of antimicrobial peptides (AMPs) was developed. AMP genes were fused to a heat-resistant CL7 tag using the SLOPE method, and cloned into Escherichia coli and Pichia pastoris expression vectors. Twenty E. coli and ten P. pastoris expression vectors were constructed. Expression supernatants were heated, heteroproteins were removed, and fusion proteins were purified by nickel affinity (Ni-NTA) chromatography. Fusion proteins were digested on the column using human rhinovirus (HRV) 3C protease, and AMPs were released and further purified. Five AMPs (1, 2, 6, 13, 16) were purified using the E. coli expression system, and one AMP (13) was purified using the P. pastoris expression system. Inhibition zone and minimum inhibitory concentration (MIC) tests confirmed that one P. pastoris⌐-derived and two E. coli-derived AMPs have the inhibition activity. The MIC of AMP 13 and 16 from E. coli was 24.2 μM, and the MIC of AMP 13 from P. pastoris was 8.1 μM. The combination of prokaryotic and eukaryotic expression systems expands the universality of the developed method, facilitating screening of a large number of biologically active AMPs, establishing an AMP library, and producing AMPs by industrialised biological methods.

In the age of synthetic biology, plastid engineering requires a nimble platform to introduce novel synthetic circuits in plants. While effective for integrating relatively small constructs into the plastome, plastid engineering via homologous recombination of transgenes is over 30 years old. Here we show the design-build-test of a novel synthetic genome structure that does not disturb the native plastome: the 'mini-synplastome'. The mini-synplastome was inspired by dinoflagellate plastome organization, which is comprised of numerous minicircles residing in the plastid instead of a single organellar genome molecule. The first mini-synplastome in plants was developed in vitro to meet the following criteria: (i) episomal replication in plastids; (ii) facile cloning; (iii) predictable transgene expression in plastids; (iv) non-integration of vector sequences into the endogenous plastome; and (v) autonomous persistence in the plant over generations in the absence of exogenous selection pressure. Mini-synplastomes are anticipated to revolutionize chloroplast biotechnology, enable facile marker-free plastid engineering, and provide an unparalleled platform for one-step metabolic engineering in plants.

Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup.

Circulating tumor cells (CTCs) are associated with a higher risk of metastasis in tumor patients. The adhesion and arrest of CTCs at a secondary site is an essential prerequisite for the occurrence of tumor metastasis. CTC reattachment has shown to be dependent on microtentacle (McTN) formation in vivo. However, the specific molecular mechanism of McTN formation in suspended cancer cells remains largely unclear. Here, we demonstrated that the activation of Notch-1 signaling triggers McTN formation to facilitate cell reattachment in suspended cell culture conditions. Moreover, molecular mechanistic studies revealed that McTN formation is governed by the balance between microtubule-driven outgrowth and actomyosin-driven cell contractility. The activation of Notch-1 downregulates the acetylation level of microtubules via the Cdc42/HDAC6 pathway, which contributes to microtubule polymerization. Simultaneously, Notch-1 signaling-induced Cdc42 activation also reduced phosphorylation of myosin regulatory light chain, leading to cell contractility attenuation. Altogether, these results defined a novel mechanism by which Notch-1 signaling disturbs the balance between the expansion of microtubules and contraction of the cortical actin, which promotes McTN formation and cell reattachment. Our findings provide a new perspective on the effective therapeutic target to prevent CTC reattachment.

Sepsis is a dysregulated systemic response to infection, and no effective treatment options are available. Acacetin is a natural flavonoid found in various plants, including Sparganii rhizoma, Sargentodoxa cuneata and Patrinia scabiosifolia. Studies have revealed that acacetin potentially exerts anti-inflammatory and antioxidative effects on sepsis. In this study, we investigated the potential protective effect of acacetin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation and molecular docking. First, we found that acacetin significantly suppressed pathological damage and pro-inflammatory cytokine expression in mice with LPS-induced fulminant hepatic failure and acute lung injury, and in vitro experiments further confirmed that acacetin attenuated LPS-induced M1 polarization. Then, network pharmacology screening revealed EGFR, PTGS2, SRC and ESR1 as the top four overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 20 enriched biological processes and signalling pathways associated with the therapeutic effects of acacetin on sepsis. Further network pharmacological analysis indicated that gap junctions may be highly involved in the protective effects of acacetin on sepsis. Finally, molecular docking verified that acacetin bound to the active sites of the four targets predicted by network pharmacology, and in vitro experiments further confirmed that acacetin significantly inhibited the upregulation of p-src induced by LPS and attenuated LPS-induced M1 polarization through gap junctions. Taken together, our results indicate that acacetin may protect against sepsis via a mechanism involving multiple targets and pathways and that gap junctions may be highly involved in this process.

Acute liver injury (ALI) is associated with poor survival in patients with sepsis. During sepsis, the liver is the main site of bacterial endotoxin-induced inflammation. Lipopolysaccharide (LPS) promotes caspase-4/5/11 activation, leading to pyroptosis, a major sepsis driver. This study aimed to identify novel drugs that can control hepatocyte caspase-4/5/11 activation during sepsis. We performed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells and established an LPS-induced ALI mouse model. We identified samotolisib (ST), a novel dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, by screening a library of 441 pyroptosis compounds with known targets, which dose-dependently inhibited caspase-11 activation and N-terminal fragment of gasdermin D (GSDMD-NT) generation, reducing RAW 264.7 cell pyroptosis. In mice, ST preconditioning improved survival, attenuated LPS-induced serum alanine aminotransferase and aspartate aminotransferase activity, and inhibited severe liver inflammation and damage. Importantly, ST treatment activated Nedd4, which directly interacts with and mediates caspase-11 ubiquitination and degradation. This was largely abrogated by insulin-like growth factor 1. ST ameliorated LPS-induced hepatotoxicity by inhibiting caspase-11/GSDMD-NT pyroptosis signaling via regulating PI3K/AKT/mTOR/Nedd4 signaling. Hence, ST may play a key role in the prevention of liver injury in patients with sepsis.

The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer.

Down syndrome (DS) is caused by the trisomy of chromosome 21. Among the many disabilities found in individuals with DS is an increased risk of early-onset Alzheimer's disease (AD). Although higher oxidative stress and an upregulation of amyloid β (Aβ) peptides from an extra copy of the APP gene are attributed to the AD susceptibility, the relationship between the two factors is unclear. To address this issue, we established an in vitro cellular model using neurons differentiated from DS patient-derived induced pluripotent stem cells (iPSCs) and isogenic euploid iPSCs. Neurons differentiated from DS patient-derived iPSCs secreted more Aβ compared to those differentiated from the euploid iPSCs. Treatment of the neurons with an antioxidant, N-acetylcysteine, significantly suppressed the Aβ secretion. These findings suggest that oxidative stress has an important role in controlling the Aβ level in neurons differentiated from DS patient-derived iPSCs and that N-acetylcysteine can be a potential therapeutic option to ameliorate the Aβ secretion.

Metabolic reprograming is now a recognized hallmark of cancer. The prostate-specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene-conditional knockout (KO) mouse carcinogenesis model is highly desirable for studying prostate cancer biology and prevention due to its close resemblance of primary molecular defects and histopathological features of human prostate cancer. We have recently published macromolecular profiling of this model by proteomics and transcriptomics, denoting a preeminence of inflammation and myeloid suppressive immune cell features. Here, we performed metabolomic analyses of Pten-KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa).

The wide spread of plasmid-mediated colistin resistance by mobile colistin resistance (MCR) in Enterobacteriaceae severely limits the clinical application of colistin as a last-line drug against bacterial infection. The identification of colistin potentiator from natural plants or their compound preparation as antibiotic adjuncts is a new promising strategy to meet this challenge.

In the present work, research was carried out to explore the correlation between the high-density lipoprotein cholesterol (HDL-C)/apolipoprotein A-I (apoA-I) ratio and serum free triiodothyronine (FT3) and their interaction on the risk of coronary artery disease (CAD).

To investigate the effects of lead exposure and IGF1R inhibitor AG1024 on the expression of IGF1R and IGFBP3 in PC12 cells. It is clear that the mechanism of the related proteins inducing AD is regulated by them, thus providing theoretical guidance for the prevention and treatment of lead poisoning.

Liver hepatocellular carcinoma (LIHC) is one of the most common malignant tumors. However, the etiology and exact molecular mechanism of LIHC are still not fully understood, which makes it urgent for us to further study the molecular events behind.

The objective of this study was to investigate how cellulase or/and lactic acid bacteria (LAB) affected the fermentation characteristic and microbial community in wet brewer's grains (WBG) and corn stover (CS) mixed silage.

The increasing elderly population and wide use of magnetic capsule endoscopy (MCE) have led to more attention to elderly patients.

Faba bean is an important cool-season edible legume crop that is constantly threatened by abiotic stresses such as drought. The basic leucine zipper (bZIP) gene family is one of the most abundant and diverse families of transcription factors in plants. It regulates plant growth and development and plays an important role in the response to biotic and abiotic stresses. In this study, we identified 18 members of the faba bean bZIP transcription factor family at the genome-wide level based on previous faba bean drought stress transcriptome sequencing data. A phylogenetic tree was constructed to group the 18 VfbZIP proteins into eight clades. Analysis of cis-acting elements in the promoter region suggested that these 18 VfbZIPs may be involved in regulating abiotic stress responses such as drought. Transcriptome data showed high expression of seven genes (VfbZIP1, VfbZIP2, VfbZIP5, VfbZIP7, VfbZIP15, VfbZIP17, and VfbZIP18) in the drought-tolerant cultivar under drought stress, in which VfbZIP1, VfbZIP2, and VfbZIP5 were consistently expressed as detected by quantitative real-time polymerase chain reaction (qRT-PCR) compared to the transcriptome data. Ectopic overexpression of the three VfbZIPs in tobacco, based on the potato Virus X (PVX) vector, revealed that VfbZIP5 enhanced the drought tolerance. Overexpressed VfbZIP5 in plants showed lower levels of proline (PRO), malondialdehyde (MDA), and peroxidase (POD) compared to those overexpressing an empty vector under 10 days of drought stress. Protein-protein interaction (PPI) analysis showed that VfbZIP5 interacted with seven proteins in faba bean, including VfbZIP7 and VfbZIP10. The results depict the importance of VfbZIPs in response to drought stress, and they would be useful for the improvement of drought tolerance.

Polycystic ovary syndrome (PCOS) is a lifelong metabolic disorder and the most common cause of anovulatory infertility affecting women in reproductive age. Our recent study reported that apolipoprotein C3 (ApoC3) could be a potential diagnostic serum marker for metabolism disturbance in PCOS patients, but whether it is present in the ovaries and what role it plays has not yet been described.

Quinoa is of great interest because it is cold- and drought-resistant; however, little research has been performed on quinoa under high relative humidity (RH) stress. In this study, quinoa seedlings of a highly HR-resistant variety ("Dianli-439") and a sensitive variety ("Dianli-969") were subjected to morphological and physiological measurements and metabolome and transcriptome analyses to investigate their response to high RH stress. In total, 1060 metabolites were detected, and lipids and flavonoids were the most abundant, with 173 and 167 metabolites, respectively. In total, 13,095 differentially expressed genes were identified, and the results showed that abscisic acid, auxin, and jasmonic-acid-related genes involved in plant hormone signaling may be involved in the response of quinoa seedlings to high RH stress. The analysis of the transcription factors revealed that the AP2/ERF family may also play an important role in the response to high RH stress. We identified the possible regulatory mechanisms of the hormone signaling pathways under high RH stress. Our findings can provide a basis for the selection and identification of highly resistant quinoa varieties and the screening of the metabolite-synthesis- and gene-regulation-related mechanisms in quinoa in response to RH stress.