Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

Production improvement of FK506 in Streptomyces tsukubaensis by metabolic engineering strategy.

AIMS: Study of the effect of isoleucine on the biosynthesis of FK506 and modification of its producing strain to improve the production of FK506. METHODS AND RESULTS: Metabolomics analysis was conducted to explore key changes in the metabolic processes of Streptomyces tsukubaensis Δ68 in medium with and without isoleucine. In-depth analysis revealed that the shikimate pathway, methylmalonyl-CoA, and pyruvate might be the rate-limiting factors in FK506 biosynthesis. Overexpression of involved gene PCCB1 in S. tsukubaensis Δ68, a high-yielding strain Δ68-PCCB1 was generated. Additionally, the amino acids supplement was further optimized to improve FK506 biosynthesis. Finally, FK506 production was increased to 929.6 mg L-1, which was 56.6% higher than that in the starter strain, when supplemented isoleucine and valine at 9 and 4 g L-1, respectively. CONCLUSIONS: Methylmalonyl-CoA might be the key rate-limiting factors in FK506 biosynthesis and overexpression of the gene PCCB1 and further addition of isoleucine and valine could increase the yield of FK506 by 56.6%.

[Diagnosis and treatment of divided nevus of the penis in children: A case report and literature review].

OBJECTIVE: To explore the diagnosis and treatment of divided nevus of the penis (DNP) in children. METHODS: We retrospectively analyzed the clinical data on a case of DNP treated by surgical resection and transplantation of free skin graft of the inner preputial plate, and searched PubMed, CNKI and Wanfang database prior to March 2021 for relevant literature, followed by analysis of the clinical characteristics, diagnosis and treatment of DNP. RESULTS: The free skin graft on the left side of the glans survived well. Postoperative pathology showed the DNP to be a complex pigmented nevus. The patient was followed up for 3 months, during which no obvious color difference was observed in the appearance of the glans, and nor evident abnormality in the function and sensation of the penis. A total of 12 studies meeting the inclusion criteria were retrieved from the databases, reporting the clinical features, diagnosis and treatment of 36 cases of DNP. Most of the lesions were found between 6 and 15 years old. Preoperative diagnostic methods included skin biopsy, puncture biopsy, and electronic dermatoscopy, surgical treatments involved transplantation of free skin graft of the inner preputial plate, transplantation of free skin graft of oral mucosa, direct resection and suturing, dressing change after resection, and laser therapy. The postoperative pathological types of DNP included intradermal nevus, mixed nevus, melanocytic nevus, blue nevus, epithelioid melanocytoma, and malignant melanoma. All the patients were successfully treated with excellent prognosis. CONCLUSION: Divided nevus of the penis in children is a rare type of pigmented nevus. Dermoscopy can effectively improve the accuracy of clinical diagnosis of the disease. Surgical treatment of DNP before puberty is recommended, and transplantation of free skin graft of the inner prepuce is one of the effective methods for its treatment, with the advantages of minor trauma, less blood loss during and after operation, and good cosmetic effect.

TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy.

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

Pulmonary toxicity and RNA sequencing analyses of mouse in response to exposure to cellulose nanofibrils.

OBJECTIVE: The growing applications of nanocelluloses in the fields of advanced nanocomposites, electronics, and medical devices necessitate investigation of their potential adverse effects on human health. The lungs are the primary and the most important route for the entry of nanocelluloses into the human body in occupational settings. However, data on the pulmonary toxicity of cellulose nanofibrils (CNFs) and its molecular mechanism are limited. This study investigated the pulmonary toxicity of CNFs and its genomic expression using the RNA sequencing approach. MATERIALS AND METHODS: Female C57BL/6 mice were administered CNFs at 50 µg/mouse by oropharyngeal aspiration. Samples were collected at 3 and 14 days after exposure to CNFs (DAEC). RESULTS: At three DAEC, the microscopic sections of lungs revealed a significant inflammatory response. In terms of gene expression alterations, 94 genes were up-regulated, and 107 genes were down-regulated. Most of these differentially expressed genes were involved in the inflammatory and immune responses, including chemokines, NK cells, killer cell lectin-like receptors, CD antigens, T cell-specific GTPases, immunity-related GTPase family M members, and interferon-induced proteins encoding genes. However, only 9 and 26 genes at 14 DAEC were significantly up- and down-regulated, respectively. CONCLUSIONS: The pathological analysis of lung sections and the analysis of sequencing data suggested that the homeostasis of mice lungs was restored at 14 DAEC. The findings of this study provide insights into the pulmonary toxicity, and underlying toxicological mechanisms, caused by exposure to CNFs, and are useful for the assessment of the potential toxicity of nanocelluloses.

[Correlation of micropenis with abnormal chromosomal karyotype in peripheral blood lymphocytes].

OBJECTIVE: To explore the relationship between micropenis and chromosomal karyotype abnormality. METHODS: We collected the clinical data on 375 children with congenital micropenis treated in Wuhan Children's Hospital from July 2018 to April 2020, analyzed their chromosomal karyotype in the peripheral blood lymphocytes and investigated the correlation of chromosomal karyotype abnormality with micropenis. RESULTS: Of the 375 cases of micropenis, 28 (7.5%) were found with chromosomal karyotype abnormality, including 21 cases of abnormal sex chromosomal karyotype (2 cases of 47,XXY, 1 case of 47,XYY, 1 case of 48,XXXY, 12 cases of 46,X,Yqh-, 4 cases of 46,X,Yqh+, and 1 case of 46,X,inv［Y］［p11q11］), accounting for 75% of the total cases of abnormal karyotype. Autosomal karyotype abnormality was detected in 7 cases, constituting 25% of the total cases of abnormal karyotype, including 2 cases of 46,XY,inv (9)(p12q13), 1 case of 46,XY,14pstk +, 1 case of 46,XY,15cenh +, 1 case of 46,XY,15ps +, 1 case of 46,XY,13pstk +, and 1 case of 46,XY,1qh +. The detection rate of abnormal sex chromosomal karyotype was significantly higher than that of autosomal abnormal karyotype. CONCLUSIONS: Chromosomal karyotype abnormality, especially the abnormal karyotype of sex chromosome, can cause the abnormality of the reproductive organ, which may be one of the important causes of micropenis.

Kinetics of 5-hydroxymethylfurfural formation in the sugar-amino acid model of Maillard reaction.

BACKGROUND: As a potential health hazard, 5-hydroxymethylfurfural (HMF) has been detected in thermally processed foods high in sugar and amino acids. In order to analyze HMF quantitatively and investigate the kinetics of its formation, high-performance liquid chromatography was employed to determine the content of HMF in six sugar-amino acid thermal reaction models. RESULTS: In thermal reaction models, formation of HMF was significantly affected by sugar and amino acid composition, pH value and heating conditions. HMF formation increased with increasing sugar and amino acid (cysteine excepted) content, temperature and reaction time. A maximum amount of HMF of 1.50 g kg-1 was detected in the sucrose-glutamic acid model at 110 °C and 6 h. Low pH value and added acidic amino acids promoted the formation of HMF, especially in the sucrose-containing system. CONCLUSION: HMF formation followed first-order kinetics in four models, including the model of glucose-cysteine, glucose-glutamic acid, glucose-leucine and sucrose-leucine. In contrast, HMF formation followed zero-order kinetics in the model of sucrose-glutamic acid. The quantity of HMF increased as the quantity of sugar and amino acid increased (cysteine excepted) in six tested models. © 2018 Society of Chemical Industry.

[Clinical characterization of incomplete testicular torsion in children].

OBJECTIVE: To analyze the clinical characteristics of incomplete testicular torsion (ITT) in children in order to gain a deeper insight into the disease. METHODS: This retrospective study included 37 children with ITT treated in our hospital from April 2007 to April 2017. We analyzed the clinical characteristics and results of physical examination, laboratory examination, ultrasonography and treatment. RESULTS: The patients were aged 1－14 (mean 5.7) years, with a high incidence of ITT at 2－4 and 12－14 years and a disease course of 12－96 (48 ± 8) hours. Preoperative color Doppler ultrasonography showed reduced blood flow signals in the affected testis in 31 cases (83.8%) and transverse testis with normal blood flow signals in the other 6 (16.2%). Anticlockwise torsion was found in 27 cases (72.9%), clockwise torsion in 10 (27.1%), 90-degree torsion in 7 (18.9%), 180-degree torsion in 20 (54.0%), 270-degree torsion in 10 (27.1%), intravaginal torsion in 31 (83.8%) and extravaginal torsion in 6 (16.2%). According to Arda's three grades of testicular tissue bleeding, 16 cases (43.3%) were categorized as grade Ⅰ and 21 (56.7%) as grade Ⅱ, and so the affected testes were preserved in all the cases during the operation. The patients were followed up for 12 months postoperatively, which revealed testicular atrophy in 6 cases (16.2%). CONCLUSIONS: ITT occurs in children at a young age, of less than 360 degrees in all cases, mostly 180 degrees, and the survival rate of the affected testis is high after surgery. Reduction in testicular blood flow signals at preoperative color Doppler examination is an important indication in the diagnosis of the disease.

[Laparoscopic orchiopexy for inguinal palpable cryptorchidism].

OBJECTIVE: To investigate the feasibility and advantages of laparoscopic orchiopexy in the treatment of inguinal palpable cryptorchidism. METHODS: This study included 773 cases of inguinal palpable cryptorchidism with 869 undescended testes, 218 on the left, 459 on the right and 96 bilaterally. The patients were aged 6 months to 8 years, averaging 20 months. The surgical procedures involved cutting open the posterior peritoneal wall with the ultrasonic scalpel, dissecting the spermatic cord close to the inferior pole of the kidney, separating the posterior peritoneum from the vas deferens, severing the testicular gubernaculum, pulling the testis back into the abdominal cavity and, with the vas deferens protected, bringing the testis down into the scrotum and getting it fixed. RESULTS: All the operations were successfully performed, with an average operation time of 34.8 ± 5.4 minutes and no conversion to open surgery. Ipsilateral patent processus vaginalis was found in 692 (89.5%) of the 773 cases, and contralateral concealed hernia in 233 (34.4%) of the 677 cases of unilateral cryptorchidism, which were all treated by high ligation of the hernial sac. There was no subcutaneous emphysema intraoperatively or vomiting, abdominal distension, wound bleeding and obvious pain postoperatively. The patients were followed up for 6 to 18 months, during which, regular Doppler ultrasonography revealed that the testes were located in the scrotum with no testicular retraction and atrophy, inguinal hernia or hydrocele. CONCLUSIONS: Laparoscopic orchiopexy is safe and effective for the treatment of inguinal palpable cryptorchidism, and meanwhile can be used for the detection and management of contralateral concealed hernia and the prevention of metachronous inguinal hernia.

[The Study of the Effect and Mechanism of Glucagon Like Peptide-1 in Bleomycin-induced Pulmonary Fibrosis in Mice].

OBJECTIVE: To investigate the potential value and mechanisms of glucagon like peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2 mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days after BLM infusion, the number of total cells, macrophages and neutrophils, lymphocytes, and the content of transforming growth factor-beta 1 (TGF-ß1) in bronchoalveolar lavage fluid (BALF) were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. Real time(RT)-qPCR and Western blot were used to evaluate the expression of α-smooth muscle actin (α-SMA) and vascular cell adhesion molecule-1 (VCAM-1). The phosphorylation of nuclear factor-kappa B (NF-κB) p65 was also assessed by Western blot. DNA binding of NF-κB p65 was measured through TransAMTMNF-κB p65 transcription factor ELISA kit. RESULTS: GLP-1 reduced inflammatory cells infiltration and the content of TGF-ß1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM-induced overexpression of α-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phospho-NF-κB p65/total-NF-κB p65 and NF-κB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. CONCLUSION: BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.

Genomic and physiological analysis reveals versatile metabolic capacity of deep-sea Photobacterium phosphoreum ANT-2200.

Bacteria of the genus Photobacterium thrive worldwide in oceans and show substantial eco-physiological diversity including free-living, symbiotic and piezophilic life styles. Genomic characteristics underlying this variability across species are poorly understood. Here we carried out genomic and physiological analysis of Photobacterium phosphoreum strain ANT-2200, the first deep-sea luminous bacterium of which the genome has been sequenced. Using optical mapping we updated the genomic data and reassembled it into two chromosomes and a large plasmid. Genomic analysis revealed a versatile energy metabolic potential and physiological analysis confirmed its growth capacity by deriving energy from fermentation of glucose or maltose, by respiration with formate as electron donor and trimethlyamine N-oxide (TMAO), nitrate or fumarate as electron acceptors, or by chemo-organo-heterotrophic growth in rich media. Despite that it was isolated at a site with saturated dissolved oxygen, the ANT-2200 strain possesses four gene clusters coding for typical anaerobic enzymes, the TMAO reductases. Elevated hydrostatic pressure enhances the TMAO reductase activity, mainly due to the increase of isoenzyme TorA1. The high copy number of the TMAO reductase isoenzymes and pressure-enhanced activity might imply a strategy developed by bacteria to adapt to deep-sea habitats where the instant TMAO availability may increase with depth.

Surgical correction of congenital megaprepuce: a pilot study.

OBJECTIVE: Congenital megaprepuce (CMP) is a rare penile deformity that usually requires surgical correction. This study was performed to examine the efficacy of the modified Sugita procedure for repairing CMP in pediatric patients. METHODS: We retrospectively analyzed the clinical data of pediatric patients with CMP treated by a surgeon using the modified Sugita procedure in our hospital from January 2019 to April 2021. RESULTS: Twenty patients were enrolled, and their median age at surgery was 70.5 months (range, 60-96 months). All surgeries were successful, and no complications occurred during the operation. The postoperative foreskin had moderate edema in five patients, and soaking in 10% hypertonic saline resulted in disappearance of the edema within 4 to 8 weeks. The follow-up duration was 6 to 20 months (median, 10 months). No other complications occurred, such as dehiscence or hematoma. CONCLUSIONS: The modified Sugita procedure for correction of CMP produces excellent cosmesis and a low complication rate. Our study indicates that the modified Sugita procedure is a safe and feasible treatment option.

[Sarcolemma tissue of prepubertal concealed penis: pathological characterization and clinical implication].

OBJECTIVE: To evaluate the histopathological characteristics and clinical implication of sarcolemma tissue in prepubertal concealed penis. METHODS: After measurement of the penile length, 10 prepubertal children with congenital concealed penis underwent modified Devine's operation (treatment group), and another 10 normal prepubertal children received circumcision (control group). The anatomic features of the penile sarcolemma tissue was observed intraoperatively, and its fibrosis was evaluated by Masson trichrome staining. RESULTS: The penile length of the treatment group was significantly shorter than that of the control group preoperatively ([1.49 +/- 0.17 ] cm vs [4.26 +/- 0.23 ] cm, P < 0.01). The degree of penile concealment was correlated with the distal point of the attachment of its sarcolemma fibrous tissue: the closer the distal attachment point was to the coronary ditch, the more serious was penile concealment. The proportion of the area of collagen fibers in the penile sarcolemma tissue was significantly higher in the treatment group than in the control ([65.6 +/- 6.9]% vs [37.1 +/- 4.7]%, P < 0.01). CONCLUSION: Sarcolemma fibrosis was obvious in congenital concealed penis, and the key to its management is drastic removal of all the fibrous sarcolemma tissue.

High expression of delta-like ligand 4 predicts poor prognosis after curative resection for pancreatic cancer.

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC. METHODS: Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan-Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression. RESULTS: There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14-4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22-4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42-9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04-10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001). CONCLUSIONS: High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.

Low expression of IGFBP7 is associated with poor outcome of pancreatic ductal adenocarcinoma.

BACKGROUND: Insulin-like growth factor binding protein 7(IGFBP7) has been implicated as a potential tumor suppressor in various human cancers, although the role of IGFBP7 in pancreatic ductal adenocarcinoma (PDAC) is still unknown. We investigated the expression pattern and clinical significance of IGFBP7 in human PDAC. METHODS: IGFBP7 expression was evaluated by immunohistochemistry in 190 patients with PDAC who underwent surgical tumor resection. Expression of IGFBP7 was correlated with that of p53 and Ki-67, clinicopathologic features. We also evaluated overall survival (OS) according to expression of IGFBP7 by Kaplan-Meier and Cox regression analyses. RESULTS: IGFBP7 expression was significantly downregulated in pancreatic cancer tissues compared with adjacent normal pancreas (P < 0.001) and was inversely associated with Ki-67 expression (r = -0.284, P < 0.001). No significant relationships were found for clinicopathologic features, such as diameter of tumor, node status, grade, and stage. Importantly, low expression of IGFBP7 was associated with poor OS, and this was also significant in multivariate Cox regression analysis (hazard ratio [HR], 1.38; 95 % confidence interval [95 % CI], 1.00-1.91; P = 0.05). CONCLUSIONS: We demonstrate for the first time that IGFBP7 is downregulated in pancreatic cancer, and low expression of IGFBP7 is correlated with increased proliferation and poor postoperative survival. IGFBP7 may be a tumor suppressor in PDAC.

PIWIL1 interacting RNA piR-017061 inhibits pancreatic cancer growth via regulating EFNA5.

PIWI (P element induced wimpy testis) integrating RNAs (piRNAs) are small non-coding RNAs with the length of approximately 30 nucleotides that plays crucial roles in germ cells and adult stem cells. Recently, accumulating data have shown that piRNA and PIWI proteins are involved in tumorigenesis. However, the roles of PIWI proteins and piRNAs in pancreatic cancer are still elusive. Here, we showed that piR-017061 is significantly downregulated in pancreatic cancer patients' samples and pancreatic cancer cell lines. Furthermore, we studied the function of piR-017061 in pancreatic cancer and our data revealed that piR-017061 inhibits pancreatic cancer cell growth in vitro and in vivo. Moreover, we analyzed the genomic loci around piR-017061 and identified EFNA5 as a novel target of piR-017061. Importantly, our data further revealed a direct binding between piR-017061 and EFNA5 mRNA mediated by PIWIL1. Mechanically, piR-017061 cooperates with PIWIL1 to facilitate EFNA5 mRNA degradation and loss of piR-017061 results in accumulation of EFNA5 which facilitates pancreatic cancer development. Hence, our data provided novel insights into PIWI/piRNA-mediated gene regulation and their function in pancreatic cancer. Since PIWI proteins and piRNA predominately express in germline and cancer cells, our study provided novel therapeutic strategy for pancreatic cancer treatment.

Rapid synthesis of flavor compound 4-ethyloctanoic acid under microwave irradiation.

Rapid synthesis of 4-ethyloctanoic acid by means of microwave irradiation is described. Diethyl malonate reacted with 2-ethyl-1-bromohexane in the presence of sodium ethoxide to give diethyl (2-ethylhexyl)malonate (1b). 1b was saponified in the solution of ethanol and potassium hydroxide and then acidified to form (2-ethylhexyl)propanedioic acid (1c), and 1c was heated and decarboxylized to give 4-ethyloctanoic acid (1d). The influence of reaction temperature and reaction time on the yield of 1b and the effect of reaction time on the yield of 1c and 1d were investigated in order to optimize the synthetic conditions. The relative optimal conditions for the synthesis of 1b were a mole ratio of sodium to diethyl malonate to 2-ethylhexyl bromide of 0.1:0.11:0.11, a reaction temperature of 80-85 °C, and a reaction time of 2-2.5 h. The yield of 1b was about 79%. 1b was saponified for 30 min and then acidified to form 1c, and the yield of 1c was 96%. 1c was heated for 16 min at 180°C to give 1d, and the yield of 1d was about 90%. The overall yield of 1d is 70% under microwave irradiation. The reaction time was reduced greatly. In order to compare the result of microwave irradiation with that of an oil bath, the reactions were also performed in an oil bath. The structures of intermediates, product and by-product were confirmed by HRMS, (1)H NMR, (13)C-NMR and IR.

Pulsed Laser Ablation in Water Synthesis of Black TiO2-Graphene Oxide Nanocomposites and the Enhanced Photocatalytic Performance.

Black TiO2-graphene oxide (GO) nanocomposites are synthesized via the pulsed laser ablating TiO2 powders and GO in deionized water. The simple process enables the preparation of black TiO2 nanoparticles and anchors them onto the GO sheet in one step. The TiO2-GO nanocomposites exhibit greatly enhancement for photocatalytic degradation of Rhodamine B (RB) dye in comparison with the pristine and the ablated black TiO2. The heterojunction structure plays an important role in efficient charge separation, which reduces the recombination of photogenerated electrons and holes. The unique two-dimensional structure of GO enables the composite to have a large specific surface area, and prevents the agglomeration of TiO2 nanoparticles, which are beneficial to the photocatalytic performance of the composite.

Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk.

BACKGROUND: Disease-related single nucleotide polymorphisms (SNPs) based genetic risk score (GRS) has been proven to provide independent inherited risk other than family history in multiple cancer types. AIM: To evaluate the potential of GRS in the prediction of pancreatic cancer risk. METHODS: In this case-control study (254 cases and 1200 controls), we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma (PDAC) risk in the Chinese population. The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject (personal genotyping information of the SNPs) and was weighted by external odd ratios (ORs). RESULTS: GRS was significantly different in cases and controls (1.96 ± 3.84 in PDACs vs 1.09 ± 0.94 in controls, P < 0.0001). Logistic regression revealed GRS to be associated with PDAC risk [OR = 1.23, 95% confidence interval (CI): 1.13-1.34, P < 0.0001]. GRS remained significantly associated with PDAC (OR = 1.36, 95%CI: 1.06-1.74, P = 0.015) after adjusting for age and sex. Further analysis revealed an association of increased risk for PDAC with higher GRS. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to have PDAC (OR: 1.99, 95%CI: 1.30-3.04, P = 0.002). Participants with intermediate GRS (1.0-1.9) were 39% more likely to have PDAC (OR: 1.39, 95%CI: 1.03-1.84, P = 0.031). A positive trend was observed (P trend = 0.0006). CONCLUSION: GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.

Isolation and identification of the umami peptides from shiitake mushroom by consecutive chromatography and LC-Q-TOF-MS.

Umami is critical to the taste of shiitake mushroom. To isolate and identify umami peptides, fractions from hydrolyzed dried shiitake mushroom were separated by ultrafiltration, gel filtration chromatography (GFC), and reversed-phase high-performance liquid chromatography (RP-HPLC). Separations were combined with sensory evaluations (grading and taste dilution analysis) and analysis of electronic tongue, which were used to identify the most umami component in shiitake mushroom. Low-molecular-weight fractions (MW < 3 kDa) have the strongest flavor in the shiitake mushroom hydrolysate. In the 3 subfractions separated from low-molecular-weight fractions (MW < 3 kDa) by GFC, the second subfraction (F2) was selected for RP-HPLC analysis. The first peak (G1) in RP-HPLC was identified by LC-Q-TOF-MS, and 2 tripeptides and 3 dipeptides were identified. The amino acid sequence of these peptides were Gly-Cys-Gly, Glu-Pro-Glu, Cys-Met, Val-Phe, and Gly-Glu.