C–H Amination of Purine Derivatives via Radical Oxidative Coupling

An oxidative coupling reaction between purines and alkyl ethers/benzyl compounds was developed to synthesize a series of N9 alkylated purine derivatives using n-Bu4NI as a catalyst and t-BuOOH as an oxidant. This protocol uses commercially available, inexpensive catalysts and oxidants and has a wide range of substrates with a simple operation

C–H Amination of Purine Derivatives via Radical Oxidative Coupling

An oxidative coupling reaction between purines and alkyl ethers/benzyl compounds was developed to synthesize a series of N9 alkylated purine derivatives using <i>n</i>-Bu₄NI as a catalyst and <i>t</i>-BuOOH as an oxidant. This protocol uses commercially available, inexpensive catalysts and oxidants and has a wide range of substrates with a simple operation

Image1_Comparison of Gene Expression Between Resistant and Susceptible Families Against VPAHPND and Identification of Biomarkers Used for Resistance Evaluation in Litopenaeus vannamei.TIF

Acute hepatopancreatic necrosis disease (AHPND) has caused a heavy loss to shrimp aquaculture since its outbreak. Vibrio parahaemolyticus (VPAHPND) is regarded as one of the main pathogens that caused AHPND in the Pacific white shrimp Litopenaeus vannamei. In order to learn more about the mechanism of resistance to AHPND, the resistant and susceptible shrimp families were obtained through genetic breeding, and comparative transcriptome approach was used to analyze the gene expression patterns between resistant and susceptible families. A total of 95 families were subjected to VPAHPND challenge test, and significant variations in the resistance of these families were observed. Three pairs of resistant and susceptible families were selected for transcriptome sequencing. A total of 489 differentially expressed genes (DEGs) that presented in at least two pairwise comparisons were screened, including 196 DEGs highly expressed in the susceptible families and 293 DEGs in the resistant families. Among these DEGs, 16 genes demonstrated significant difference in all three pairwise comparisons. Gene set enrichment analysis (GSEA) of all 27,331 expressed genes indicated that some energy metabolism processes were enriched in the resistant families, while signal transduction and immune system were enriched in the susceptible families. A total of 32 DEGs were further confirmed in the offspring of the detected families, among which 19 genes were successfully verified. The identified genes in this study will be useful for clarifying the genetic mechanism of shrimp resistance against Vibrio and will further provide molecular markers for evaluating the disease resistance of shrimp in the breeding program.</p

Table_1_Comparative Transcriptome Analysis Reveals the Adaptation Mechanism to High Salinity in Litopenaeus vannamei.docx

As an euryhaline commercial species, the Pacific white shrimp Litopenaeus vannamei can be cultured under a wide range of salinities. However, different families showed various tolerance to high salinity. In order to elucidate the underlying mechanisms, a comparative transcriptome approach was used to find the differences between tolerant families and susceptible families at the transcriptional level. There were 98 and 58 differentially expressed genes (DEGs) between tolerant and susceptible families under normal and high-salinity conditions, respectively. The DEGs upregulated in tolerant families were mostly enriched in the biological process of response to a stimulus. Nine crustacyanin (CRCN)-encoding genes in this Gene Ontology (GO) term showed significantly higher expression levels in the tolerant families than those in susceptible families, suggesting that crustacyanins might play important roles in shrimp tolerance to high salinity. After high-salinity treatment, a total of 233 and 109 DEGs were identified from tolerant and susceptible families, respectively. Serine-type endopeptidase activity, serine-type peptidase activity, and serine hydrolase activity were the top three GO terms in the tolerant families after high-salinity treatment. Further analysis illustrated that these three GO terms were also the top three enriched GO terms for the DEGs specifically upregulated in the tolerant families after high-salinity stress. Meanwhile, four genes annotated in serine proteases families in these three GO terms were upregulated in the tolerant families but not changed in the susceptible families after high-salinity stress. These results indicated that serine proteases should play key roles in shrimp tolerance to high salinity. This study provides important information for understanding the mechanism of shrimp tolerance to high-salinity stress and would be useful for further molecular breeding of shrimp varieties with high-salinity tolerance.</p

Table_2_Comparative Transcriptome Analysis Reveals the Adaptation Mechanism to High Salinity in Litopenaeus vannamei.docx

As an euryhaline commercial species, the Pacific white shrimp Litopenaeus vannamei can be cultured under a wide range of salinities. However, different families showed various tolerance to high salinity. In order to elucidate the underlying mechanisms, a comparative transcriptome approach was used to find the differences between tolerant families and susceptible families at the transcriptional level. There were 98 and 58 differentially expressed genes (DEGs) between tolerant and susceptible families under normal and high-salinity conditions, respectively. The DEGs upregulated in tolerant families were mostly enriched in the biological process of response to a stimulus. Nine crustacyanin (CRCN)-encoding genes in this Gene Ontology (GO) term showed significantly higher expression levels in the tolerant families than those in susceptible families, suggesting that crustacyanins might play important roles in shrimp tolerance to high salinity. After high-salinity treatment, a total of 233 and 109 DEGs were identified from tolerant and susceptible families, respectively. Serine-type endopeptidase activity, serine-type peptidase activity, and serine hydrolase activity were the top three GO terms in the tolerant families after high-salinity treatment. Further analysis illustrated that these three GO terms were also the top three enriched GO terms for the DEGs specifically upregulated in the tolerant families after high-salinity stress. Meanwhile, four genes annotated in serine proteases families in these three GO terms were upregulated in the tolerant families but not changed in the susceptible families after high-salinity stress. These results indicated that serine proteases should play key roles in shrimp tolerance to high salinity. This study provides important information for understanding the mechanism of shrimp tolerance to high-salinity stress and would be useful for further molecular breeding of shrimp varieties with high-salinity tolerance.</p

Image_1_Comparative Transcriptome Analysis Reveals the Adaptation Mechanism to High Salinity in Litopenaeus vannamei.tif

As an euryhaline commercial species, the Pacific white shrimp Litopenaeus vannamei can be cultured under a wide range of salinities. However, different families showed various tolerance to high salinity. In order to elucidate the underlying mechanisms, a comparative transcriptome approach was used to find the differences between tolerant families and susceptible families at the transcriptional level. There were 98 and 58 differentially expressed genes (DEGs) between tolerant and susceptible families under normal and high-salinity conditions, respectively. The DEGs upregulated in tolerant families were mostly enriched in the biological process of response to a stimulus. Nine crustacyanin (CRCN)-encoding genes in this Gene Ontology (GO) term showed significantly higher expression levels in the tolerant families than those in susceptible families, suggesting that crustacyanins might play important roles in shrimp tolerance to high salinity. After high-salinity treatment, a total of 233 and 109 DEGs were identified from tolerant and susceptible families, respectively. Serine-type endopeptidase activity, serine-type peptidase activity, and serine hydrolase activity were the top three GO terms in the tolerant families after high-salinity treatment. Further analysis illustrated that these three GO terms were also the top three enriched GO terms for the DEGs specifically upregulated in the tolerant families after high-salinity stress. Meanwhile, four genes annotated in serine proteases families in these three GO terms were upregulated in the tolerant families but not changed in the susceptible families after high-salinity stress. These results indicated that serine proteases should play key roles in shrimp tolerance to high salinity. This study provides important information for understanding the mechanism of shrimp tolerance to high-salinity stress and would be useful for further molecular breeding of shrimp varieties with high-salinity tolerance.</p

Deoxygenative Cross-Coupling of C(aryl)–O and C(amide)O Electrophiles Enabled by Chromium Catalysis Using Bipyridine Ligand

Deoxygenative cross-coupling between unactivated C–O and unsaturated CO electrophiles remains an unsolved challenge in synthetic chemistry. Here, we report the deoxygenative cross-coupling of C–O/CO electrophiles by reaction of unactivated aryl esters with unsaturated amides, enabled by chromium catalysis. Inexpensive and simple CrCl3 salt combined with bipyridine ligand, magnesium reductant, and chlorosilane, shows high reactivity in promoting the deoxygenative coupling between C–O and CO bonds involving hydrogen transfer. This reaction provides a strategy to form pharmaceutically interesting diarylmethylated amines, by forging C­(sp2)–C­(sp3) bonds with impeding the competing ester homocoupling and carbonyl reduction that usually occur under reductive conditions. Mechanistic studies based on high-resolution mass spectrometry analysis and deuterium-labeling experiments indicate that cleavage of ester C–O bonds by Cr and subsequent silylation leads to the formation of arylated silachromate, which regioselectively adds to carbonyls of amides through reductive elimination and deoxygenative hydrogen transfer, resulting in the reductive cross-coupling of C­(aryl)–O and C­(amide)O electrophiles

Knockdown of DDR2 inhibited proliferation, activation and induced necrosis in HSCs and changed the body features of rats.

<p>(a) Hoechst 33342 and PI staining of necrosis of HSC-T6 cells with acetaldehyde treatment for the indicated times. Live cells show a low level of fluorescence; apoptotic cells show a higher level of blue fluorescence, and necrotic cells show low-blue and high-red fluorescence. Arrows show necrotic cells. (b) Immunohistochemical staining for α-SMA in liver tissue (400×magnification); arrows show positive stained cells. (c) Quantification of Hoechst 33342 and PI staining. 0, cells without acetaldehyde treatment (n = 5). (d) Quantification of MTT results (n = 8). (e) Quantification of immunohistochemical staining for α-SMA (n = 20). (f) Quantification of biochemistry (n = 10). (g) Body weight and (h) liver weight to body weight (n = 10 each). Data are mean ± SD. *P<0.05, **P<0.01.</p

Ethic committe approval in English.

IntroductionWe investigated the epidemiology of Cytochrome P450 (CYP) 3A4 genotype and the relationship between CYP3A4 genotype and alcohol drinking habits.Materials and methodsA single-centered retrospective study was conducted on 630 patients who underwent CYP3A4*1G genetic testing. Their relevant information on epidemiology and etiology was collected. Laboratory testing, including CYP3A4*1G genotype, liver function tests, and serum lipid measurements were performed. Bi-variate logistic regressions were used to examine the relationship between variables. The relationship between alcohol drinking and CYP3A4*1G genotype was estimated. Demographic and clinical features were analyzed. Participants with drinking history were divided into non-heavy drinking and heavy drinking groups. Liver function and dyslipidemia of participants with drinking histories were compared between CYP3A4*1G mutation (GA+AA) and wild-type (GG) groups.ResultsParticipants with CYP3A4*1G mutation(GA+AA) had an increased adjusted odds ratio (AOR) of 2.56 (95% CI, 1.4–4.65; P = 0.00) for alcohol abuse when compared with participants without CYP3A4 mutation (GG). In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury levels and serum lipid levels between CYP3A4*1G mutant and wild-type groups. Patients with CYP3A4*1G mutation had an increased AOR of cardiac-vascular diseases and malignant diseases compared with patients without CYP3A4*1G mutation. The epidemiology had no difference between GA and AA group.ConclusionThe study indicated that there was association between alcohol drinking and CYP3A4*1G genetic mutation. In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury and dyslipidemia between CYP3A4*1G mutant and wild-type groups. CYP3A4*1G mutation was also related to cardiac-vascular diseases and malignant diseases.</div