MTF1 has the potential as a diagnostic and prognostic marker for gastric cancer and is associated with good prognosis

Purpose Metal Regulatory Transcription Factor 1 (MTF1) can be an essential transcription factor for heavy metal response in cells and can also reduce oxidative and hypoxic stresses in cells. However, the current research on MTF1 in gastric cancer is lacking. Methods Bioinformatics techniques were used to perform expression analysis, prognostic analysis, enrichment analysis, tumor microenvironment correlation analysis, immunotherapy Immune cell Proportion Score (IPS) correlation and drug sensitivity correlation analysis of MTF1 in gastric cancer. And qRT-PCR was used to verify MTF1 expression in gastric cancer cells and tissues. Results MTF1 showed low expression in gastric cancer cells and tissues, and low expression in T3 stage compared with T1 stage. KM prognostic analysis showed that high expression of MTF1 was significantly associated with longer overall survival (OS), FP (first progression) and PPS (post-progression survival) in gastric cancer patients. Cox regression analysis showed that MTF1 was an independent prognostic factor and a protective factor in gastric cancer patients. MTF1 is involved in pathways in cancer, and the high expression of MTF1 is negatively correlated with the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs. Conclusion MTF1 is relatively lowly expressed in gastric cancer. MTF1 is also an independent prognostic factor for gastric cancer patients and is associated with good prognosis. It has the potential to be a diagnostic and prognostic marker for gastric cancer (AU)

Chiral bifunctional organocatalysts for enantioselective synthesis of 3-substituted isoindolinones.

A series of chiral bifunctional organocatalysts were prepared and used for enantioselective synthesis of 3-substituted isoindolinones from 2-formylarylnitriles and malonates through aldol-cyclization rearrangement tandem reaction in excellent yields and enantioselectivites (up to 87% yield and 95% ee) without recrystallization. In this investigation, we found that chiral tertiary-amine catalysts with a urea group can afford 3-substituted isoindolinones both in higher yields (87% vs. 77%) and enantioselectivities (95% ee vs. 46% ee) than chiral bifunctional phase-transfer catalysts.

MTF1 has the potential as a diagnostic and prognostic marker for gastric cancer and is associated with good prognosis.

PURPOSE: Metal Regulatory Transcription Factor 1 (MTF1) can be an essential transcription factor for heavy metal response in cells and can also reduce oxidative and hypoxic stresses in cells. However, the current research on MTF1 in gastric cancer is lacking. METHODS: Bioinformatics techniques were used to perform expression analysis, prognostic analysis, enrichment analysis, tumor microenvironment correlation analysis, immunotherapy Immune cell Proportion Score (IPS) correlation and drug sensitivity correlation analysis of MTF1 in gastric cancer. And qRT-PCR was used to verify MTF1 expression in gastric cancer cells and tissues. RESULTS: MTF1 showed low expression in gastric cancer cells and tissues, and low expression in T3 stage compared with T1 stage. KM prognostic analysis showed that high expression of MTF1 was significantly associated with longer overall survival (OS), FP (first progression) and PPS (post-progression survival) in gastric cancer patients. Cox regression analysis showed that MTF1 was an independent prognostic factor and a protective factor in gastric cancer patients. MTF1 is involved in pathways in cancer, and the high expression of MTF1 is negatively correlated with the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs. CONCLUSION: MTF1 is relatively lowly expressed in gastric cancer. MTF1 is also an independent prognostic factor for gastric cancer patients and is associated with good prognosis. It has the potential to be a diagnostic and prognostic marker for gastric cancer.

A systematic review and meta-analysis of long noncoding RNA 00963 expression and prognosis and clinicopathological characteristic in human cancers.

BACKGROUND: Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. In this meta-analysis, data from diverse malignancies were analyzed to determine whether LINC00963 expression levels were associated with clinical prognosis and immune infiltration in pan-cancer. MATERIALS AND METHODS: The eligible studies were identified from several electronic databases from the inception to July 2022 through systematic research. LINC00963 expression and survival were estimated using pooled odds ratios and hazard ratios with 95% CI. We used the Kaplan-Meier method and COX analysis for survival analysis. In addition, Spearman's correlation analysis was used to uncover any correlation between LINC00963 and microsatellites instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), immune checkpoint biomarkers, and the related genes of mismatch repair (MMR). RESULTS: Our findings indicated that overexpression of LINC00963 was related to poor overall survival (OS) (HR =1.32, 95% CI, 1.09-1.59, P = 0.004). The TCGA database also found that abnormal expression of LINC00963 was linked to overall survival in various cancers. Moreover, there is an association between LINC00963 expression and MSI, TMB, and MMR in malignancies of various types. CONCLUSION: The results of this study indicate that LINC00963 may serve as a prognostic biomarker and a therapeutic target for cancer. By using it, cancer diagnoses can be improved, treatment targets discovered, and prognostic questions improved.

Antibacterial Activity of Squaric Amide Derivative SA2 against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA)-caused infection is difficult to treat because of its resistance to commonly used antibiotic, and poses a significant threat to public health. To develop new anti-bacterial agents to combat MRSA-induced infections, we synthesized novel squaric amide derivatives and evaluated their anti-bacterial activity by determining the minimum inhibitory concentration (MIC). Additionally, inhibitory activity of squaric amide 2 (SA2) was measured using the growth curve assay, time-kill assay, and an MRSA-induced skin infection animal model. A scanning electron microscope and transmission electron microscope were utilized to observe the effect of SA2 on the morphologies of MRSA. Transcriptome analysis and real-time PCR were used to test the possible anti-bacterial mechanism of SA2. The results showed that SA2 exerted bactericidal activity against a number of MRSA strains with an MIC at 4-8 µg/mL. It also inhibited the bacterial growth curve of MRSA strains in a dose-dependent manner, and reduced the colony formation unit in 4× MIC within 4-8 h. The infective lesion size and the bacterial number in the MRSA-induced infection tissue of mice were reduced significantly within 7 days after SA2 treatment. Moreover, SA2 disrupted the bacterial membrane and alanine dehydrogenase-dependent NAD+/NADH homeostasis. Our data indicates that SA2 is a possible lead compound for the development of new anti-bacterial agents against MRSA infection.

Chiral Cyclopropenimine-catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,ß-Unsaturated Isoxazoles.

A highly efficient asymmetric Michael addition of bulky glycine imine to α,ß-unsaturated isoxazoles has been achieved by using 5 mol% of chiral cyclopropenimine as a chiral organo-superbase catalyst under mild conditions. Michael adducts were obtained in excellent yields (up to 97%) and stereoselectivities (up to >99 : 1 dr and 98% ee). A significant solvent effect was found in these chiral organosuperbase catalyzed asymmetric Michael reactions. Gram-scale preparation of Michael adducts and their transformations are realized to provide corresponding products without loss of stereoselectivities. The configurations of Michael adduct was determined by single-crystal X-ray diffraction analysis.

PSC-MSC-Derived Exosomes Protect against Kidney Fibrosis In Vivo and In Vitro through the SIRT6/ß-Catenin Signaling Pathway.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) has a major impact on the quality of life of patients, and renal fibrosis is a critical pathological change in the disease. It is very important to control the process of renal fibrosis to improve the quality of life of patients with CKD. The pathological mechanism of renal fibrosis is very complicated, and the current treatment strategy also has many flaws. METHODS AND RESULTS: To explore a better treatment, we collected exosomes from pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSC) and verified their therapeutic effect on renal fibrosis through in vivo and in vitro experiments. In this study, we found that PSC-MSC-derived comes could prevent the epithelial differentiation of NRK-52E cells, and with increasing exosome concentrations, the effect was improved. Furthermore, PSC-MSC-derived exosomes could reduce the pathological process of renal fibrosis, reduce inflammatory reactions and improve renal function in UUO mice. Moreover, the protective effect of exosomes against renal fibrosis may be achieved by increasing the expression of SIRT6 and decreasing the expression of ß-catenin and its downstream products. CONCLUSIONS: These findings suggest the possibility of PSC-MSC-derived exosomes as a new, effective therapeutic tool for kidney fibrosis.

[Corrigendum] Preliminary research on the effects and mechanisms of umbilical cord­derived mesenchymal stem cells in streptozotocin­induced diabetic retinopathy.

Following the publication of this article, the authors have realized that grant number published in the 'Funding' section of their paper was written incorrectly: The grant number for the support the authors received from the Health Commission of Hubei Province Scientific Research Project should have been written as 'WJ2019F038' instead of 'WJ2009F038'. The authors apologize to the funders of their research project, and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 46: 849­858, 2020; DOI: 10.3892/ijmm.2020.4623].

Preliminary research on the effects and mechanisms of umbilical cord­derived mesenchymal stem cells in streptozotocin­induced diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes, and a common cause of blindness in working­age individuals. Mesenchymal stem cell (MSC) transplantation has been considered a promising intervention therapy for DR, wherein the differentiation of MSCs into nerve cells plays an essential role. However, research into the role of MSCs in DR treatment remains incomplete, and the mechanisms of retinal repair at the molecular level have yet to be clarified. In the present study, all­trans retinoic acid (ATRA) was used to promote the proliferation of rat umbilical cord (UC)­derived MSCs and their differentiation into nerve cells. Furthermore, the effects and mechanisms of UC­MSCs with or without ATRA treatment were investigated in rats subjected to streptozocin (STZ)­induced DR. The results demonstrated that the transplantation of UC­MSCs treated with or without ATRA attenuated DR in rats, and alleviated retinal tissue damage and apoptosis. In addition, the transplantation of UC­MSCs treated with or without ATRA attenuated angiogenesis and inflammation in the retina by regulating the levels of relevant cytokines. UC­MSCs treated with ATRA exerted a more prominent therapeutic effect than the untreated UC­MSCs. On the whole, these findings indicate that UC­MSCs alleviate STZ­induced DR in rats by regulating angiogenesis and the inflammatory response at the molecular level. Thus, the findings of the present study may provide a theoretical basis for the application of MSCs in the treatment of DR.

Bifunctional phase-transfer catalysts for synthesis of 2-oxazolidinones from isocyanates and epoxides.

A series of bifunctional phase-transfer catalysts (PTCs) were synthesized to catalyze the [3 + 2] coupling reaction of isocyanates and epoxides to afford 2-oxazolidinones in good to high yields (up to 92% yield) using PhCl as a solvent at 100 °C within 12 h. These bifunctional PTCs were easily prepared from commercially available tertiary-primary diamines and isocyanates (or isothiocyanates, mono-squaramides, respectively) in two simple steps with good modularity and demonstrated high efficiency (2.5 mol% catalyst-loading). The synergistic interaction of the quaternary ammonium salt center and hydrogen-bond donor group in the catalyst with the substrate is crucial to this atom-economic reaction.

CRISPR-Cas9 assisted functional gene editing in the mushroom Ganoderma lucidum.

The genetic manipulation of basidiomycete mushrooms is notoriously difficult and immature, and there is a lack of research reports on clustered regularly interspaced short palindromic repeat (CRISPR) based gene editing of functional genes in mushrooms. In this work, Ganoderma lucidum, a famous traditional medicinal basidiomycete mushroom, which produces a type of unique triterpenoid-anti-tumor ganoderic acids (GAs), was used, and a CRISPR/CRISPR-associated protein-9 nuclease (Cas9) editing system for functional genes of GA biosynthesis was constructed in the mushroom. As proof of concept, the effect of different gRNA constructs with endogenous u6 promoter and self-cleaving ribozyme HDV on ura3 disruption efficiency was investigated at first. The established system was applied to edit a cytochrome P450 monooxygenase (CYP450) gene cyp5150l8, which is responsible for a three-step biotransformation of lanosterol at C-26 to ganoderic acid 3-hydroxy-lanosta-8, 24-dien-26 oic acid. As a result, precisely edited cyp5150l8 disruptants were obtained after sequencing confirmation. The fermentation products of the wild type (WT) and cyp5150l8 disruptant were analyzed, and a significant decrease in the titer of four identified GAs was found in the mutant compared to WT. Another CYP gene involved in the biosynthesis of squalene-type triterpenoid 2, 3; 22, 23-squalene dioxide, cyp505d13, was also disrupted using the established CRISPR-Cas9 based gene editing platform of G. lucidum. The work will be helpful to strain molecular breeding and biotechnological applications of G. lucidum and other basidiomycete mushrooms.

Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines.

Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.

BES1 is activated by EMS1-TPD1-SERK1/2-mediated signaling to control tapetum development in Arabidopsis thaliana.

BES1 and BZR1 were originally identified as two key transcription factors specifically regulating brassinosteroid (BR)-mediated gene expression. They belong to a family consisting of six members, BES1, BZR1, BEH1, BEH2, BEH3, and BEH4. bes1 and bzr1 single mutants do not exhibit any characteristic BR phenotypes, suggesting functional redundancy of these proteins. Here, by generating higher order mutants, we show that a quintuple mutant is male sterile due to defects in tapetum and microsporocyte development in anthers. Our genetic and biochemical analyses demonstrate that BES1 family members also act as downstream transcription factors in the EMS1-TPD1-SERK1/2 pathway. Ectopic expression of both TPD1 and EMS1 in bri1-116, a BR receptor null mutant, leads to the accumulation of non-phosphorylated, active BES1, similar to activation of BES1 by BRI1-BR-BAK1 signaling. These data suggest that two distinctive receptor-like kinase-mediated signaling pathways share BES1 family members as downstream transcription factors to regulate different aspects of plant development.

Tandem grinding reactions involving aldol condensation and Michael addition in sequence for synthesis of 3,4,5-trisubstituted isoxazoles.

A one-pot, base-catalyzed, tandem grinding process involving carrying out aldol condensation and Michael addition in sequence to produce 3,4,5-trisubstituted isoxazoles from 3,5-dimethyl-4-nitroisoxazole, aromatic aldehydes and activated methylene compounds has been developed. In the presence of 10 mol% of pyrrolidine, aldol condensations of 3,5-dimethyl-4-nitroisoxazole with various aromatic aldehydes were performed with 3-10 minutes of grinding to provide 5-styryl-3-methyl-4-nitroisoxazoles in good to quantitative yields without further purification. Then, Michael additions between 5-styryl-3-methyl-4-nitroisoxazoles and activated methylene compounds (including ethyl 2-nitroacetate and alkyl 2-cyanoacetates) were carried out in the presence of 10 mol% of Et3N in the same mortar with 3-5 minutes of continuous grinding to produce 3,4,5-trisubstituted isoxazoles in good to excellent yields.

Highly Efficient Michael Reactions of Nitroolefins by Grinding Means.

AIM AND OBJECTIVE: The direct ß-functionalization of trans-ß-nitroolefins by Michael reaction is regarded as an efficient way to provide precursors for ß-functional amines. However, Michael additions by grinding means with solvent-free conditons are rarely reported. We have developed facile access to ß-functional nitroalkanes by grinding means under solvent-free conditions. MATERIALS AND METHODS: From commercially available materials including ethyl 2-nitroacetate, alkyl 2-cyanoacetates and malononitrile, the grinding reactions between these above-mentioned activated methylenecompounds and various trans-ß-nitroolefins were performed at room temperature and solvent-free conditions. RESULTS: A highly efficient direct Michael reaction of nitroolefins by simple grinding means has been developed. Various trans-nitrostyrenes were easily converted into corresponding ß-functional nitroalkanes in excellent yields within 5~10 min (up to 36 examples). CONCLUSION: Herein, we have developed a simple and efficient way to ß-functional nitroalkanes through Michael reactions by grinding means. The grinding Michael reaction is fast, clean and stable and these Michael adducts could be easily converted into the other amino compounds served as building blocks in organic synthesis.

Enantioselective amination of nitroolefins under base-free and water-rich conditions using chiral bifunctional phase-transfer catalysts.

The direct enantioselective amination of nitroolefins has been performed with l-tert-leucine-derived squaramide-scaffold bifunctional phase-transfer catalysts under base-free and water-rich conditions with low catalyst loading (0.5-1 mol%) to provide 2-aminonitroalkanes in good yields (up to 96%) and enantioselectivities (up to 93% ee).

Serine/arginine rich splicing factor 2 expression and clinic pathological features indicating a prognostic factor in human hepatocellular carcinoma patients.

BACKGROUND: This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). METHODS: One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. RESULTS: In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (P< 0.05). The expression of SRSF2 in HCC was not associated with gender (χ2= 0.014, P= 0.906), age (χ2= 0.007, P= 0.931), tumor size (χ2= 3.566, P= 0.059) and T stage (χ2= 2.708, P= 0.100), and was significantly correlated with tumor differentiation (χ2= 9.687, P= 0.007), lymph node metastasis (χ2= 4.827, P= 0.028), distal metastasis (χ2= 9.235, P= 0.002), tumor, node, metastasis (TNM) stage (χ2= 3.978, P= 0.046), portal vein invasion and serum alpha-fetoprotein (χ2= 14.919, P= 0.000). The expression of SRSF2 protein in hepatocellular carcinoma was positively correlated (r = 0.704, P< 0.05) with serum alpha-fetoprotein through Pearson analysis. The survival rates of SRSF2 overexpressing hepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). CONCLUSION: SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients.

A New Class of Glucosyl Thioureas: Synthesis and Larvicidal Activities.

A novel series of glucosyl thioureas were synthesized in good overall yields (up to 37% over four steps) from d-glucose and primary amines, and their larvicidal activities toward Mythimna separata Walker were also investigated. This new class of glucosyl thioureas demonstrated low to moderate growth inhibition activity of Mythiman separata Walker, with a growth inhibitory rate of up to 47.5% at a concentration of 100.0 mg/L in acetone.