Convenient synthesis of <i>N</i>-sulfonyl α-hydroxyamides via DMSO oxidation of <i>N</i>-alk-1-ynylsulfonamides

N-Arenesulfonyl α-hydroxyamides are conveniently synthesized from N-arylethynylsulfonamides (ynamides) via oxidation with dimethyl sulfoxide (DMSO) in the presence of equivalent of trifluoromethanesulfonic acid (TfOH) followed by treatment with water. In this reaction, ynamides are activated by protonation with TfOH and then undergo double DMSO nucleophilic addition and subsequent hydrolysis. Investigations on the substrate scope indicate N-arenesulfonyl and arylethynyl substituted ynamides proceed the oxidation well. Compared to the previous methods, the current method realizes the direct conversion from N-arylethynylsulfonamides to N-arenesulfonyl α-hydroxyamides with mild DMSO as a nucleophilic oxidant in the presence of strong acid trifluoromethanesulfonic acid.</p

Isolation and Stereospecific Synthesis of Janolusimide B from a New Zealand Collection of the Bryozoan <i>Bugula flabellata</i>

NMR-directed screening of New Zealand marine organisms has led to the isolation of the modified tripeptide janolusimide B from the common invasive bryozoan <i>Bugula flabellata</i>. The structure was established by NMR and MS analysis, degradative hydrolysis and derivatization, and stereoselective fragment synthesis. The bryozoan natural product is an <i>N-</i>methyl analogue of janolusimide, previously reported from the Mediterranean nudibranch <i>Janolus cristatus</i>, a species known to prey upon bryozoa

Distinguishing Thermal and Electronic Effects in Ultrafast Optical Spectroscopy Using Oxide Heterostructures

Measuring time-resolved photoexcited properties in semiconductors is critical to the design and improvement of light-harvesting devices. Although ultrafast pump–probe spectroscopy offers a promising route to understand carrier recombination mechanisms and quantify lifetimes, thermal contributions to the transient optical response can be significant and need to be properly accounted for to isolate carrier-induced contributions. We demonstrate the use of broadband ultrafast optical spectroscopy on type I heterostructures as a means to isolate transient effects that are solely thermal in nature. Specifically, we use transient absorption and reflectance spectroscopy to measure the time-resolved optoelectronic changes in photoexcited epitaxial bilayers of LaFeO₃/LaMnO₃ and monolithic thin films of these materials. Experiments and complementary numerical modeling reveal that thermal effects dominate the transient absorption and reflectance spectra above the band gap. Fitting the dynamics with a thermal diffusion model yields thermal conductivities of 6.4 W m^–1 K^–1 for LaFeO₃ and 2.2 W m^–1 K^–1 for LaMnO₃. In LaFeO₃, an additional photoinduced absorption feature below the band gap at ∼1.9 eV is assigned primarily to photoexcited carriers and persists for over 3 ns. This work provides a direct demonstration of how thermal and electronic contributions can be separated in transient optical spectroscopies, enabling new insights into dynamical optical properties of semiconductors

Additional file 1 of Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels

Additional file 1: Figure S1. The protective effect of Rab32 knockdown on mitochondria. A Representative transmission electron microscope image showing mitochondria morphological changes accompanying Schwann cell pyroptosis induced by LPS/ATP. Scale bar = 2 µm. B Quantitative data of the average number of mitochondria per unit area. C Quantitative data of the average volume of mitochondria per unit area. **p < 0.01 compared to the LA/shRab32 group. *p < 0.05 compared to the LA/shRab32 group. Figure S2. Quantification of LDH release indicating Schwann cell damage. **p < 0.01 compared to the LA group. *p < 0.05 compared to the LA group. Figure S3. Representative transmission electron microscope image showing morphological changes accompanying Schwann cell pyroptosis induced by LPS/ATP. The black arrows represent the pores on the cell membrane, which is also one of the characteristic signs of pyroptosis. Scale bar = 2 µm. Figure S4. The impact of Rab32 on mitochondrial morphology in Schwann cells following peripheral nerve injury. A Representative transmission electron microscope image showing mitochondrial morphological changes accompanying Schwann cell pyroptosis induced by PNI. Scale bar = 2 µm. B Quantitative data of the average number of mitochondria per unit area. C Quantitative data of the average volume of mitochondria per unit area. **p < 0.01 compared to the PNI/shRab32 group. *p < 0.05 compared to the PNI/shRab32 group. Figure S5. Evaluation of the effect of MitoQ on pyroptosis in peripheral nerve injury. A Western blotting analysis was conducted to evaluate the levels of pyroptosis-associated proteins in nerve tissues. β-actin was used as an internal control. B–D Levels of pyroptosis-associated proteins were quantified based on semi-quantitative band analysis. E Representative immunofluorescence images displaying NLRP3 (red) and S100β (green) in nerve tissues. **p < 0.01 compared to the PNI/M group. *p < 0.05 compared to the PNI/M group. Scale bar = 20 µm

Integrated Multi-Omics Techniques and Network Pharmacology Analysis to Explore the Material Basis and Mechanism of Simiao Pill in the Treatment of Rheumatoid Arthritis

The Simiao pill (SMP) is a classic prescription that has shown anti-inflammatory, analgesic, and immunomodulatory effects and is clinically used to treat inflammatory diseases, such as rheumatoid arthritis (RA) and gouty arthritis, for which the effects and mechanism of action remain largely unknown. In this study, serum samples from RA rats were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry based metabolomics technology and liquid chromatography with tandem mass spectrometry proteomics technology together with network pharmacology to explore the pharmacodynamic substances of SMP. To further verify the above results, we constructed a fibroblast-like synoviocyte (FLS) cell model and administered phellodendrine for the test. All these clues suggested that SMP can significantly reduce the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in complete Freund’s adjuvant rat serum and improve the degree of foot swelling; combined with metabolomics, proteomics, and network pharmacological technology, it is determined that SMP plays a therapeutic role through the inflammatory pathway, and phellodendrine is found to be one of the pharmacodynamic substances. By constructing an FLS model, it is further determined that phellodendrine could effectively inhibit the activity of synovial cells and reduce the expression level of inflammatory factors by downregulating the expression level of related proteins in the TLR4-MyD88-IRAK4-MAPK signal pathway to alleviate joint inflammation and cartilage injury. Overall, these findings suggested that phellodendrine is an effective component of SMP in the treatment of RA

The putative cis regulatory elements responsive to serum deprivation is resided in the DRAM promoter region flanking −19/+28 nucleotides.

<p>(A) Hep3B and HepG2 cells were transiently transfected with reporter plasmids containing truncated versions of the promoter region of the <i>DRAM</i> gene as indicated. Luc-DCP is defined as the reporter containing the shortest promoter region (−19∼+28). (B) The core promoter region contains a putative NF-κB binding site. Transcription factor binding sites presented in the core promoter region (-19∼+28) were predicated by web software TFSEARCH and MatInspector and the mutation or deletion plasmids were generated using the site-directed mutagenesis method. (C) Mutation or deletion of the NF-κB binding site does not affect the core promoter activity.</p

The chromatin remodeling factor Brg-1 is essential for serum starvation-induced DRAM expression.

<p>(A) Brg-1 is bound to the proximal region of the DRAM promoter. ChIP assays were performed in Hep3B and HepG2 cells. (B) Serum deprivation enhances Brg-1 and Pol II binding to the DRAM promoter locus. (C) Depletion of Brg-1 using specific targeting shRNA abolishes serum deprivation induced DRAM expression.</p

Azelaic Acid Regulates the Renin–Angiotensin System and Improves Colitis Based on Network Pharmacology and Experimentation

Inflammatory bowel disease (IBD), which encompasses Crohn’s disease and ulcerative colitis, has a complicated etiology that might be brought on by metabolic dysbiosis. Previous metabonomic studies have found a correlation between decreased azelaic acid (AzA) and IBD. Herein, data from the Metabolomics Workbench showed that the content of AzA decreased in IBD patients (PR000639) and dextran sulfate sodium (DSS)-induced mice (PR000837). The effects of AzA on IBD were then examined using a DSS-induced mouse model, and the results demonstrated that AzA alleviated clinical activity, decreased pro-inflammatory cytokine production, and reduced CD4+CD25+Foxp3+Treg percentages in mesenteric lymph nodes. Through network pharmacology analysis, we discovered 99 candidate IBD-associated genes that are potentially regulated by AzA. After the enrichment analysis of the candidate genes, the renin–angiotensin system (RAS) pathway was one of the most substantially enriched pathways. Additionally, AzA reversed the increased expression of important RAS components (ACE, ACE2, and MAS1L) following DSS induction, suggesting that AzA exerts therapeutic effects possibly via the RAS pathway. This study suggests that AzA may be a promising drug for treating IBD

Serum deprivation induces DRAM expression in liver cancer cells.

<p>(A) mRNA level of the DRAM gene upon serum deprivation at different time points were quantified by real-time RT-PCR in HepG2 cells. (B) DRAM expression in Hep3B cells is similar to that observed in HepG2 cells. (C) Analysis of the DRAM protein expression in HepG2 cells. CD166 served as a positive control for serum starvation induced protein expression. Cells were grown to 70% confluency in DMEM containing 10% FBS. These cells were washed with PBS and fed with DMEM media omitting FBS for various time points. The resulting cells were harvested and the total RNAs and whole cell lysates were extracted and the expression of DRAM mRNA and protein was examined by qRT-PCR or western blot. GAPDH were used as an internal control. (D) Inhibition of protein synthesis does not affect serum starvation-induced DRAM expression in HepG2 cells. Cells were treated with CHX (10 mM) under serum deprivation for 24 hrs, and total RNA was extracted for analysis of the DRAM expression by real-time PCR. All results are presented as means±S.D. of three independent experiments. **, <i>p</i><0.01 level using t-test.</p

Serum deprivation induces changes in histone modification at the DRAM promoter locus in Hep3B cells.

<p>Hep3B cells were prepared for chromatin IP (ChIP) assays. The chromatin DNAs were immunoprecipitated with antibodies specific to H3K4me3 (A), anti-di-acetyl-H3 (B), anti-H3K9me2 (C) and anti-tetra-acetyl-H4 (D), and the enriched DNA fragments flanking the DRAM promoter were analyzed by quantitative PCR. Data were presented as the amount of DNA recovered by specific antibodies relative to DNA enriched by the appropriate IgG controls. The results were expressed as the means±standard deviations of three independent experiments. *: P<0.05.</p