Mechanism of the components compatibility of Scutellariae Radix and Coptidis Rhizoma on mice with hyperlipidemia by regulating the Cyp4a family.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (Scutellariae Radix, SR) and Coptis chinensis Franch (Coptidis Rhizoma, CR) is a classic herbal pair used in many Traditional Chinese Medicine formulations in the treatment of hyperlipidemia (HLP). As effective ingredients of the drug pair, the effects and mechanisms of berberine and baicalin in the treatment of HLP in the form of components compatibility are still unclear. AIM OF THE STUDY: To explore the mechanism of the components compatibility of SR and CR in the treatment of HLP. MATERIALS AND METHODS: The HLP model was established by a high-fat diet. Serum biochemical indexes were detected. Transcriptomics and metabolomics were detected. RT-PCR and Western Blot were used to analyze the effect of RA on the expression of the Cyp4a family during the treatment of HLP. RESULTS: Berberine-baicalin (RA) has a good effect in the treatment of HLP. RA can significantly reduce the body weight and liver weight of HLP, reduce the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein (HDL-C). Through transcriptomic analysis, RA significantly reversed the gene expression of Cyp4a10, Cyp4a12 b, Cyp4a31, and Cyp4a32 in cytochrome P450 family 4 subfamily a (Cyp4a) which related to fatty acid degradation in the liver of HLP mice. The results of fatty acid detection showed that RA could significantly regulate heptanoic acid, EPA, adrenic acid, DH-γ-linolenic acid, and DPA in the cecum of HLP mice. The Cyp4a family genes regulated by RA are closely related to a variety of fatty acids regulated by RA. RT-PCR confirmed that RA could regulate Cyp4a mRNA expression in HLP mice. WB also showed that RA can regulate the protein expression level of Cyp4a. CONCLUSION: The components compatibility of SR and CR can effectively improve the blood lipid level of HLP mice, its mechanism may be related to regulating Cyp4a gene expression and affecting fatty acid degradation, regulating the level of fatty acid metabolism in the body.

Characterizing immune variation and diagnostic indicators of preeclampsia by single-cell RNA sequencing and machine learning.

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

P1 of turnip mosaic virus interacts with NOD19 for vigorous infection.

P1 protein, the most divergent protein of virus members in the genus Potyvirus of the family Potyviridae, is required for robust infection and host adaptation. However, how P1 affects viral proliferation is still largely elusive. In this work, a total number of eight potential P1-interacting Arabidopsis proteins were identified by the yeast-two-hybrid screening using the turnip mosaic virus (TuMV)-encoded P1 protein as the bait. Among which, the stress upregulated NODULIN 19 (NOD19) was selected for further characterization. The bimolecular fluorescent complementation assay confirmed the interaction between TuMV P1 and NOD19. Expression profile, structure, and subcellular localization analyses showed that NOD19 is a membrane-associated protein expressed mainly in plant aerial parts. Viral infectivity assay showed that the infection of turnip mosaic virus and soybean mosaic virus was attenuated in the null mutant of Arabidopsis NOD19 and NOD19-knockdown soybean seedlings, respectively. Together, these data indicate that NOD19 is a P1-interacting host factor required for robust infection.

[Effects of different carbon addition modes on the soil priming effect of a subtropical Phyllostachys edulis forest under nitrogen deposition]. / æ°®æ²‰é™ä¸‹ä¸åŒç¢³æ·»åŠ æ¨¡å¼å¯¹äºšçƒ­å¸¦æ¯›ç«¹æž—åœŸå£¤æ¿€å‘æ•ˆåº”çš„å½±å“.

Priming effect (PE) plays an important role in regulating terrestrial soil carbon (C) cycling, but the impact of different C addition modes on the PE in subtropical forest ecosystems with increasing nitrogen (N) deposition is unclear. In this study, we investigated the effects of C addition patterns (single or repeated C addition) on soil PE by adding 13C-labeled glucose for 90 d in an incubation experiment with different levels of N application (0, 20, and 80 kg N·hm-2·a-1). The different patterns of glucose addition significantly increased soil organic C (SOC) mineralization and produced positive PE. Single glucose addition resulted in stronger PE than repeated addition. PE was significantly weakened with increasing N application levels, indicating that N deposition inhibited soil excitation in Phyllostachys edulis forests. The cumulative PE was significantly negatively correlated with ß-N-acetylaminoglucosidase (NAG) and peroxidase (PEO) activities, and was significantly positively correlated with microbial biomass P (MBP) and potential of hydrogen (pH). Our findings indicated that, when acting together on soil, N application and C addition could strongly affect soil C stocks by stimulating the mineralization of native soil organic matter in subtropical forests. The findings further indicated that single C addition model might overestimate the effect of exogenous readily decomposable organic C on PE and ignore the effect of N deposition on PE, which in turn would overestimate the mineralization loss of forest SOC.

Pregestational diabetes mediates the association between maternal obesity and the risk of congenital heart defects.

AIMS/INTRODUCTION: We aimed to explore whether the association between obesity and congenital heart defects (CHDs) can be mediated by maternal pregestational diabetes (PGDM). MATERIALS AND METHODS: We included 53,708 mother-infant pairs with deliveries between 2017 and 2019 from the Birth Cohort in Shenzhen. Mothers were categorized into four groups: the underweight group (body mass index [BMI] <18.5), normal weight group (18.5 ≤ BMI < 24), overweight group (24 ≤ BMI < 28) and obesity group (BMI ≥28). Multivariable logistic regression models were used to evaluate the association between BMI and CHDs. Mediation analysis was used to confirm the effect of PGDM on the association between maternal obesity and CHDs. RESULTS: The proportion of obese individuals in the Birth Cohort in Shenzhen was 2.11%. Overall, 372 (0.69%) infants were diagnosed with CHDs. Maternal obesity was associated with an increased risk of CHDs (odds ratio 1.97, 95% confidence interval 1.14-3.41). The mediation effect of PGDM on the association between maternal obesity and CHDs was significant (odds ratio 1.18, 95% confidence interval 1.06-1.32). The estimated mediation proportion was 24.83%. CONCLUSIONS: Maternal obesity was associated with increased risk for CHDs, and PGDM partially mediated the association between maternal obesity and CHDs.

Fasting plasma glucose in the first trimester is related to gestational diabetes mellitus and adverse pregnancy outcomes.

PURPOSE: To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population. METHODS: We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities. RESULTS: The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P < 0.05). The univariate analysis showed that first-trimester FPG was strongly associated with risks of outcomes including GDM, cesarean section, macrosomia, GHD, primary cesarean section, and LGA (all OR > 1, all P < 0.05), furthermore, the risks of GDM, primary cesarean section, and LGA was increasing with first-trimester FPG as early as it was at 4.19-4.63 mmol/L. The multivariable analysis showed that the risks of GDM (ORs for FPG 4.19-4.63, 4.63-5.11 and 5.11-7.0 mmol/L were 1.137, 1.592, and 4.031, respectively, all P < 0.05) increased as early as first-trimester FPG was at 4.19-4.63 mmol/L, and first-trimester FPG which was also associated with the risks of cesarean section, macrosomia and LGA (OR for FPG 5.11-7.0 mmol/L of cesarean section: 1.128; OR for FPG 5.11-7.0 mmol/L of macrosomia: 1.561; OR for FPG 4.63-5.11 and 5.11-7.0 mmol/L of LGA: 1.149 and 1.426, respectively, all P < 0.05) and with its increasing, the risks of LGA increased. Furthermore, the nomogram had a C-indices 0.771(95% CI: 0.763~0.779) and 0.770(95% CI:0.758~0.781) in training and testing validation respectively, which showed an acceptable consistency between the observed, validation and nomogram-predicted probabilities, the DAC curve analysis indicated that the nomogram had important clinical application value for GDM risk prediction. CONCLUSIONS: FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.

[Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats].

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1ß(IL-1ß), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

[Control effect of blue light on Bemisia tabaci]. / è“å ‰å¯¹è”¬èœçƒŸç²‰è™±çš„æŽ§åˆ¶ä½œç”¨.

Light is a important way in controlling vegetable pests. In this work, we examined the effects of blue light on Bemisia tabaci on cucumbers, as well as on nutrients, secondary metabolites, and resistance-related enzymes in cucumbers. Results of the direct repellent test showed that blue light had a strong repellent effect on B. tabaci, which increased with light intensity and exposure time. The repellent effect of direct light was stronger than that of transmitted light under the same light intensity and time. The population decline rate of B. tabaci was 77.7% after direct exposure to 1200 lx blue light for 5 min, being 17.4% higher than that of transmitted light. After 2 min exposure to 1750 lx blue light, the population decline rate was 41.2%, which was 10.6% higher than that of transmitted light. Under the condition of pot culture, blue light also had a good repellent effect on B. tabaci on leaves. The corrected population decline rate of B. tabaci reached 88.5% after 5 h exposure to 100 lx blue light. Blue light affected the development of B. tabaci. In addition, blue light significantly increased the contents of soluble sugar, free protein, total phenols and flavonoids in cucumber leaves, decreased the content of proline. The contents of trans-ß-farnesene, trans-2-hexenal, cis-4-heptanal, trans-ß-ocilene, D-carvone, longifolene and 3-carene, and the activities of peroxidase, catalase, superoxide dismutase, ascorbate peroxidase were significantly increased. The results suggested that blue light could drive off B. tabaci and influence the resistance of cucumber. 100 lx blue light had a good control effect on B. tabaci.

Rational Design of 2-Substituted DMAP-N-oxides as Acyl Transfer Catalysts: Dynamic Kinetic Resolution of Azlactones.

A novel concept that conversion of chiral 2-substituted DMAP into its DMAP-N-oxide could significantly enhance the catalytic activity and still be used as an acyl transfer catalyst is presented. A new type of chiral 2-substituted DMAP-N-oxides, derived from l-prolinamides, has been rationally designed, facilely synthesized, and applied in the dynamic kinetic resolution of azlactones. Using simple MeOH as the nucleophile, various l-amino acid derivatives were produced in high yields (up to 98% yield) and enantioselectivities (up to 96% ee). Furthermore, α-deuterium labeled l-phenylalanine derivative was also obtained. Experiments and DFT calculations revealed that in 2-substituted DMAP-N-oxide, the oxygen atom acted as the nucleophilic site and the N-H bond functioned as the H-bond donor. High enantioselectivity of the reaction was governed by steric factors, and the addition of benzoic acid reduced the activation energy by participating in the construction of a H-bond bridge. The theoretical chemical study indicated that only when attack directions of the chiral catalyst were fully considered could the correct calculation results be obtained. This work paves the way for the utilization of the C2 position of the pyridine ring and the development of chiral 2-substituted DMAP-N-oxides as efficient acyl transfer catalysts.

Rice immune sensor XA21 differentially enhances plant growth and survival under distinct levels of drought.

Drought is a complex stress that limits plant growth and crop production worldwide. The mechanisms by which plants coordinately respond to distinct levels of water deficits (e.g., mild, moderate or severe drought) remain elusive. Here we demonstrate that the rice immune sensor XA21 promotes survival of rice seedlings during dehydration stress. XA21 expression increases deposition of lignin and cellulose in the xylem vessels and their surrounding cells. Inhibition of aquaporin water channels by mercuric chloride eliminates XA21-mediated dehydration survival, suggesting that XA21 enables plant survival during drought, probably by protecting xylem functionality. In contrast to prevailing observations of stress tolerance genes, XA21 is also capable of enhancing rice growth during moderate drought. Thus, XA21 acts as a mediator for stress protection and plant growth under water-limiting conditions.

Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report.

BACKGROUND: Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. CASE PRESENTATION: We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. CONCLUSION: This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.

Regio- and Diastereoselective Spirocyclopropanation of Benzofuran-Derived Azadienes through 1,4-Addition-Induced Dearomatization Reaction under Mild Conditions.

A Cs2CO3-mediated [2 + 1] cycloaddition of benzofuran-derived azadienes (BDAs) with bromomalonate by using a dearomatization strategy has been developed. Through this process, BDAs serve as a potential 2-atom synthon in the construction of a range of functionalized spirocyclopropane derivatives, such as spirobenzofuran-2-cyclopropanes and spiroindane-2-cyclopropanes.

Two Nucleoporin98 homologous genes jointly participate in the regulation of starch degradation to repress senescence in Arabidopsis.

BACKGROUND: Starch is synthesized during daylight for temporary storage in leaves and then degraded during the subsequent night to support plant growth and development. Impairment of starch degradation leads to stunted growth, even senescence and death. The nuclear pore complex is involved in many cellular processes, but its relationship with starch degradation has been unclear until now. We previously identified that two Nucleoporin98 genes (Nup98a and Nup98b) redundantly regulate flowering via the CONSTANS (CO)-independent pathway in Arabidopsis thaliana. The double mutant also shows severe senescence phenotypes. RESULTS: We find that Nucleoporin 98 participates in the regulation of sugar metabolism in leaves and is also involved in senescence regulation in Arabidopsis. We show that Nup98a and Nup98b function redundantly at different stages of starch degradation. The nup98a-1 nup98b-1 double mutant accumulates more starch, showing a severe early senescence phenotype compared to wild type plants. The expression of marker genes related to starch degradation is impaired in the nup98a-1 nup98b-1 double mutant, and marker genes of carbon starvation and senescence express their products earlier and in higher abundance than in wild type plants, suggesting that abnormalities in energy metabolism are the main cause of senescence in the double mutant. Addition of sucrose to the growth medium rescues early senescence phenotypes of the nup98a-1 nup98b-1 mutant. CONCLUSIONS: Our results provide evidence for a novel role of the nuclear pore complex in energy metabolism related to growth and development, in which Nup98 functions in starch degradation to control growth regulation in Arabidopsis.

Analysis of Soybean Somatic Embryogenesis Using Chromosome Segment Substitution Lines and Transcriptome Sequencing.

Soybean is an important cash crop that is widely used as a source of vegetable protein and edible oil. The regeneration ability of soybean directly affects the application of biotechnology. In this study, we used the exogenous hormone 2,4-D to treat immature embryos. Different levels of somatic incidence were selected from the chromosome segment substitution lines (CSSLs) constructed by SN14 and ZYD00006. Transcriptome sequencing of extreme materials was performed, and 2666 differentially expressed genes were obtained. At the same time, a difference table was generated by combining the data on CSSL rearrangement. In the extreme materials, a total of 93 differentially expressed genes were predicted and were then analyzed by cluster analysis and Gene Ontology (GO) annotation. After screening and annotating the target genes, three differentially expressed genes with hormone pathways were identified. The expression patterns of the target genes were verified by real-time quantitative PCR (qRT-PCR). Haplotype polymorphism detection and linkage disequilibrium analysis were performed on the candidate gene Glyma.09g248200. This study provided more information on the regulation network of soybean somatic embryogenesis and regeneration processes, and further identified important genes in the soybean regeneration process and provided a theoretical basis for accelerating the application of biotechnology to soybean for improving its breeding efficiency.

Analysis of miRNAs Targeted Storage Regulatory Genes during Soybean Seed Development Based on Transcriptome Sequencing.

Soybeans are an important cash crop and are widely used as a source of vegetable protein and edible oil. MicroRNAs (miRNA) are endogenous small RNA that play an important regulatory role in the evolutionarily conserved system of gene expression. In this study, we selected four lines with extreme phenotypes, as well as high or low protein and oil content, from the chromosome segment substitution line (CSSL) constructed from suinong (SN14) and ZYD00006, and planted and sampled at three stages of grain development for small RNA sequencing and expression analysis. The sequencing results revealed the expression pattern of miRNA in the materials, and predicted miRNA-targeted regulatory genes, including 1967 pairs of corresponding relationships between known-miRNA and their target genes, as well as 597 pairs of corresponding relationships between novel-miRNA and their target genes. After screening and annotating genes that were targeted for regulation, five specific genes were identified to be differentially expressed during seed development and subsequently analyzed for their regulatory relationship with miRNAs. The expression pattern of the targeted gene was verified by Real-time Quantitative PCR (RT-qPCR). Our research provides more information about the miRNA regulatory network in soybeans and further identifies useful genes that regulate storage during soy grain development, providing a theoretical basis for the regulation of soybean quality traits.

Chiral DMAP-N-oxides as Acyl Transfer Catalysts: Design, Synthesis, and Application in Asymmetric Steglich Rearrangement.

A DMAP-N-oxide, featuring an α-amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O-acylated azlactones afforded C-acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP-N-oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP-N-oxides for asymmetric acyl transfer reactions.

MARCH3 attenuates IL-1ß-triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI.

The proinflammatory cytokine IL-1ß plays critical roles in inflammatory and autoimmune diseases. IL-1ß signaling is tightly regulated to avoid excessive inflammatory response. In this study, we identified the E3 ubiquitin ligase membrane-associated RING-CH-type finger 3 (MARCH3) as a critical negative regulator of IL-1ß-triggered signaling. Overexpression of MARCH3 inhibited IL-1ß-triggered activation of NF-κB as well as expression of inflammatory genes, whereas MARCH3 deficiency had the opposite effects. MARCH3-deficient mice produced higher levels of serum inflammatory cytokines and were more sensitive to inflammatory death upon IL-1ß injection or Listeria monocytogenes infection. Mechanistically, MARCH3 was associated with IL-1 receptor I (IL-1RI) and mediated its K48-linked polyubiquitination at K409 and lysosomal-dependent degradation. Furthermore, IL-1ß stimulation triggered dephosphorylation of MARCH3 by CDC25A and activation of its E3 ligase activity. Our findings suggest that MARCH3-mediated IL-1RI degradation is an important mechanism for attenuating IL-1ß-triggered inflammatory response.

Efficient synthesis of tetrazole hemiaminal silyl ethers via three-component hemiaminal silylation.

An efficient route to construct 2,5-disubstituted tetrazole hemiaminal silyl ethers via one-pot three-component hemiaminal silylation of 5-substituted tetrazoles, aldehydes, and silyl triflates was developed. Diverse 2,5-disubstituted tetrazole hemiaminal silyl ethers were obtained with 37 : 63->99 : 1 regioisomeric ratios. The regioselectivities of this reaction were significantly affected by steric hindrance and the conjugation effects of substitutions on the 5-position of tetrazoles.

Dual-Emission SG7@MOF Sensor via SC-SC Transformation: Enhancing the Formation of Excimer Emission and the Range and Sensitivity of Detection.

In this study, a water stable metal-organic framework FIR-53 is applied as a single-crystal container for anion exchange. The exceptional chemical stability and low crystallographic symmetry of FIR-53 makes it possible to determine anionic guests. Through ion exchange and single-crystal to single-crystal (SC-SC) transformation, 8-hydroxypyrene-1,3,6-trisulfonate (SG7, solvent green 7, ion form as SG73-) is introduced into the pores of FIR-53 to obtain SG7@FIR-53. Because of the spatial confinement and partition effect, SG7@FIR-53 shows the bright exciter emission of SG7 ions. Interestingly, the composite SG7@FIR-53 exhibits a sensitive fluorescence quenching response against Cr2O72- and MnO4- in aqueous solution. Especially, the detection limit toward MnO4- is as low as 0.12 ppb, which is the smallest value to date. Moreover, the prepared SG7@FIR-53 film also displays a broad response to nitro explosives in vapor/aqueous phase. Compared with the results of FIR-53, the range and sensitivity were greatly improved.

Asymmetric Synthesis of Chiral Acyclic Purine Nucleosides Containing a Hemiaminal Ester Moiety via Three-Component Dynamic Kinetic Resolution.

An efficient route to construct chiral acyclic purine nucleosides containing a hemiaminal ester moiety is reported via three-component dynamic kinetic resolution of purines, aldehydes, and acid anhydrides. The procedure provides diverse chiral acyclic purine nucleoside analogues in a regioselective manner with good yields (up to 93% yield) and excellent enantioselectivities (up to 95% ee). Furthermore, the chiral (acyloxyalkyl)-5-fluorouracil could also be generated as a potential prodrug of 5-fluorouracil.