Digital finance and M&As: An empirical study and mechanism analysis.

With the rapid growth and wide application of digital technology, enterprises have entered the digital era with both opportunities and challenges existing. Mergers and acquisitions are one of the most efficient ways to integrate resources and achieve profit growth, giving enterprises advantages in competing in the new mode of economic growth. Based on this, this research tries to explore whether the development of digital finance will contribute to the emergence of M&As activities through combining M&As data of the Chinese stock market with the digital finance inclusion index between 2012 and 2020. The results show that the development of digital finance largely influences M&As activities through lower acquirers' financial constraints. We further replace digital finance with three sub-indexes including coverage breadth, usage depth, and digitalization level to explore the impact of different dimensions of digital finance on M&As. Results show that coverage breadth plays a more important role. In addition, heterogeneity tests reveal that the relationship between the development of digital finance and M&As activities varies significantly. The influences of digital finance on private and western and central enterprises are more significant compared with state-owned and eastern enterprises. According to the study, since the development of digital finance can be an efficient way to ease financial constraints and boost M&As activities, the government should promote the development of digital finance while companies strive to make the most use of it.

Breakthrough Path of Low-Level Equilibrium of China's Policy-Oriented Financing Guarantee Market.

Policy-oriented financing guarantee schemes are widely adopted in the world to alleviate the financing difficulties of small and medium-sized enterprises. However, the development level of policy-oriented financing guarantee market in China has not reached the desired high-level equilibrium target, even though governments have issued a series of guiding policies. Accordingly, based on the evolutionary game theory, this study establishes and analyzes the game model between local governments, guarantee institutions, and banks. Then, the breakthrough effects of different paths on the low-level equilibrium of the guarantee market are simulated. The results show that strengthening superior government's performance appraisal intensity can only partially delay the "window period" of the low-level equilibrium, while adjusting local governments' compensation coefficients or increasing banks' risk sharing ratio have further synergistic effects on the realization of the high-level equilibrium. Additionally, dynamic reward and penalty mechanism of the local governments can effectively restrain the unbalanced state of financing guarantee market caused by banks' excess compensation risk, and finally impel the stabilization of the high-level equilibrium state.

A Broad-Spectrum Catalytic Amidation of Sulfonyl Fluorides and Fluorosulfates*.

A broad-spectrum, catalytic method has been developed for the synthesis of sulfonamides and sulfamates. With the activation by the combination of a catalytic amount of 1-hydroxybenzotriazole (HOBt) and silicon additives, amidations of sulfonyl fluorides and fluorosulfates proceeded smoothly and excellent yields were generally obtained (87-99 %). Noticeably, this protocol is particularly efficient for sterically hindered substrates. Catalyst loading is generally low and only 0.02 mol % of catalyst is required for the multidecagram-scale synthesis of an amantadine derivative. In addition, the potential of this method in medicinal chemistry has been demonstrated by the synthesis of the marketed drug Fedratinib via a key intermediate sulfonyl fluoride 13. Since a large number of amines are commercially available, this route provides a facile entry to access Fedratinib analogues for biological screening.

Electrooxidative and Regioselective C-H Azolation of Phenol and Aniline Derivatives.

A general and practical protocol was developed for the regioselective C-H azolation of phenol and aniline derivatives by electrooxidative cross-coupling. The reaction occurs under metal-, oxidant-, and reagent-free conditions, allowing access to a wide variety of synthetically useful heteroarene derivatives. The reaction also tolerates a broad range of functional groups and is amenable to gram-scale synthesis. Finally, a preliminary mechanistic study indicated that a radical-radical-combination pathway might be involved in the coupling reaction.

Resveratrol induced apoptosis in human gastric carcinoma SGC-7901 cells via activation of mitochondrial pathway.

BACKGROUND: Resveratrol is a natural polyphenolic compound and its anticancer effect has been receiving considerable attention. Previous studies showed that resveratrol could inhibited the growth of human gastric carcinoma cells and apoptosis induction was an important mechanism. However, whether mitochondrial pathway was involved in resveratrol-induced apoptosis in human gastric cancer was not very clear. METHODS: The cells were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Annexin V/PI staining assay, mitochondrial membrane depolarization, cell morphological assessment, cytochrome c release assay, and Western blotting assay. RESULTS: In this study, we found that resveratrol induced apoptosis in human gastric carcinoma SGC-7901 cells. Cleaved PARP was observed and caspase-3 was activated by resveratrol. Next, the mitochondrial membrane potential of cells dissipated after the cells were treated by resveratrol. Moreover, we found that pro-caspase 9 was downregulated and cytochrome c released from mitochondrial to the cytosol. We also found that the expression ratio of Bax/Bcl-2 was increased in the treated cells. We finally showed that resveratrol inhibited the proliferation of SGC-7901 xerograph in vivo. CONCLUSIONS: Collectively, our findings demonstrate that resveratrol triggers apoptosis via mitochondrial pathway in SGC-7901 cells, which provide more basis for resveratrol acting as antitumor agents in cancer therapy.

[Analysis of C.3925_3929 deletional mutations of APC gene in pedigrees with familial adenomatous polyposis].

OBJECTIVE: To analyze the characteristics of germline mutations of adenomatous polyposis coli (APC) gene in pedigrees affected with familial adenomatous polyposis (FAP). METHODS: Genomic DNA was extracted from peripheral blood samples from members of the 13 FAP pedigrees. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large fragment deletions of the APC gene. Subsequently, potential mutation was screened from all exons of the APC gene with PCR amplification and direct sequencing. RESULTS: Germline mutations have been identified in 5 FAP pedigrees, which included c.3184_3187delCAAA, c.5432C>T, c.3925_3928delAAAA and c.3925_3929del AAAAG(in two pedigrees). Small deletional mutations were found primarily in the area of AAAAG tandem repeat sequences. CONCLUSION: C.3925_3929 located in AAAAG tandem repeats is probably the hot spot for APC gene mutations, which are mostly deletional mutations, especially the 5 bp base deletion at codon 1309.

Analysis of Small Fragment Deletions of the APC gene in Chinese Patients with Familial Adenomatous Polyposis, a Precancerous Condition.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly caused by mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectal polyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-year old if total proctocolectomy is not performed. So identification of APC germline mutations has great implications for genetic counseling and management of FAP patients. In this study, we screened APC germline mutations in Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristics of Chinese FAP patients. MATERIALS AND METHODS: The FAP patients were diagnosed by clinical manifestations, family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards, genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerase chain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification (MLPA) for large duplications and/or deletions. RESULTS: We found 6 micromutations out of 14 FAP pedigrees, while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p. Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13), c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and all deletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA and two c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in the CAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5'-CCTGAACA-3' ,3'-ACAAGTCC-5 palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon 1309. CONCLUSIONS: Though there were no novel mutations found as the pathogenic gene of FAP in this study, we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especially the 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene.

Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro.

Curcumin, the major pigment of the dietary spice turmeric, has the potential for chemoprevention by promotion of apoptosis. Here, we investigated the molecular mechanisms of curcumin in glycolytic inhibition and apoptotic induction in human colorectal cancer HCT116 and HT29 cells. On the one hand, curcumin downregulated the expression and activity of hexokinase II (HKII) in HCT116 and HT29 cells in a concentration-dependent manner, but had little effect on the other key glycolytic enzymes (PFK, PGM, and LDH). On the other, curcumin induced dissociation of HKII from the mitochondria, resulting in mitochondrial-mediated apoptosis. Furthermore, the phosphorylation of mitochondrial HKII through AKT was responsible for the curcumin-induced dissociation of HKII, which was different from the mechanism of HKII inhibitor 3-BrPA. These results have important implications for the metabolism reprogramming effect and the susceptibility to curcumin-induced mitochondrial cytotoxicity through the regulation of HKII, and provide a molecular basis for the development of naturally compounds as novel anticancer agents for colorectal carcinoma.

Pseudorabies viral replication is inhibited by a novel target of miR-21.

The pseudorabies virus (PRV) is a porcine virus classified as a member of the Alphaherpesvirinae subfamily of Herpesviridae. Recent studies have confirmed that viruses regulate the gene expression in host cells. Commonly affected genes include oxidative-stress response genes, genes involved in the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) signaling pathway, and interferon- and interleukin-related genes. However, the post-transcriptional regulation of host genes following PRV infection is hitherto unclear. In this study, we used miRNA microarray approaches to assess miRNA expression in PRV-infected porcine kidney 15 cell line (PK-15), and observed that miR-21 was expressed at high level 12h after the cells were infected with PRV. Furthermore, we identified chemokine (C-X-C motif) ligand 10 (CXCL10), also named interferon-γ inducible protein-10 (IP-10), as a novel target gene of miR-21. IP-10 was down-regulated at 4h after PRV infection. PRV replication was significantly inhibited by IP-10 overexpression.

Plasma post-operative miR-21 expression in the prognosis of gastric cancers.

Tumor-associated microRNAs have been detected in serum or plasma, but whether plasma microRNA-21 (miR-21) could be a potential circulating biomarker for gastric cancer (GC) prognosis in Chinese is still uncertain. Real-time quantitative reverse transcription PCR (qRT-PCR) was employed in this study to compare the relative expression of miR-21 between pre-operative and post-operative paired plasmas from 42 patients with primary GCs. The results showed that the expression levels of miR-21 in the post-operative plasmas were significantly reduced by an average of 18.2 times in all patients when compared to the pre-operative plasmas, and by 22.1 times in the subgroup of patients without family history, while only 1.76 times in the subgroup of patients with a family history. With respect of clinicopathological characteristics, the plasma miR-21 expression was highly associated with differentiation degree and lymph node metastasis rate. The results suggested plasma miR-21 could be a novel potential biomarker for GC prognosis and evaluation of surgery outcomes, especially in patients without a family history.

[Mutation screening of LKB1 gene in familial Peutz-Jeghers syndrome patients].

OBJECTIVE: To screen for potential mutations of LKB1 gene in Chinese familial Peutz-Jeghers syndrome (PJS) patients and analyze their clinical manifestations. METHODS: Eleven PJS families were collected and genomic DNA of peripheral blood was extracted. Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands. Mutation screening of the probands were carried out by PCR and direct sequencing. Two hundred and fifty healthy adults were enrolled as normal controls, for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquid chromatography was carried out to verify the mutation identified in the patients. RESULTS: Nine germline mutations were identified in eight PJS patients, which included 7 point mutations, 1 deletion and 1 insertion. Among these, 4 were considered to be pathogenic, of which 2 were de novel, 4 were considered to be polymorphism, and 1 was uncertain. CONCLUSION: LKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients. Most mutations are point mutations.

Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population.

BACKGROUND: Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have been associated with risks of many cancers, little is known about their etiology role in gastric cancer (GC) and the potential interacting role with lifestyle factors known to damage DNA. METHODS: A population-based study was conducted in 3 counties (Jintan, Taixing and Huaian) of Jiangsu Province, the high-risk areas of GC in China. We investigated the association of polymorphisms IVS12-6T>C and IVS10+12G>A in MSH2 gene with the risk of GC and the potential gene-lifestyle interaction. RESULTS: The risk of GC was found to be associated with the IVS12-6C allele (CC vs TT, OR=2.34, 95% CI: 1.17-4.71) and IVS10+12A allele (GA or AA vs GG, OR=1.55, 95% CI: 1.14-2.21; and GA vs GG, OR=1.51, 95% CI: 1.04-2.17). Stratified analysis indicated that an increased risk of GC also was observed in: suspected familial subjects carrying the IVS12-6T>C (OR=1.68, 95% CI: 1.27-2.66) or IVS10+12G>A (OR=2.57, 95% CI: 1.53-4.10); or younger subjects carrying the IVS12-6T>C (OR=2.15, 95% CI: 1.24-3.91) or IVS10+12G>A (OR=2.23, 95% CI: 1.20-4.33); or male subjects carrying the IVS10+12G>A (OR=1.64; 95% CI: 1.10-2.54). Furthermore, the combined IVS12-6CC and IVS10+12AA genotypes also significantly increased the risk of GC (OR=2.12, 95% CI: 1.22-3.66). Statistically significant interactions were observed between: IVS10+12G>A and drinking, high pickled food or fried food intake (OR=2.32; 95% CI: 1.43-3.78, OR=2.55; 95% CI: 1.48-4.21 and OR=2.88; 95% CI: 1.70-4.94, respectively); and IVS12-6T>C and high pickled food intake or fried food intake (OR=2.65; 95% CI: 1.62-4.47 and OR=2.48; 95% CI: 1.42-4.13, respectively). CONCLUSION: The IVS10+12G>A and IVS12-6T>C polymorphisms in MSH2 gene appear to be associated with risk of GC in this Chinese population. Risk for GC, stratified by related genotypes, was further modified by drinking, high pickled food or fried food intake. Larger prospective studies are needed to confirm these findings.

Molecular characterization of the porcine STAT4 and STAT6 genes.

Signal transducers and activators of transcription (STATs) are members of a recently identified family of transcription factors that activate gene transcription in response to a number of different cytokines. STAT4 and STAT6 were activated by interleukin (IL)-12 and IL-4 stimulation, which were important for the generation of Th1 and Th2 cells. In this study, we cloned the cDNA sequences and analyzed the genomic structure of porcine STAT4 (poSTAT4) and STAT6 (poSTAT6) genes. Chromosome localization assigned these two genes to SSC15 and SSC5, and they were most closely linked to maker SWR1002 and DK. The RT-PCR revealed that both genes were expressed in eight diverse tissues, with the highest level in small intestine, followed by lung, kidney, muscle and stomach, whereas expressions in heart, liver and spleen were relatively weak. Transient transfection indicated that poSTAT4 and poSTAT6 proteins distributed throughout the whole porcine hip artery endothelial cell. A single nucleotide polymorphism (A/G), which can be recognized by restriction enzyme TaiI, was identified at the 3' untranslated region of poSTAT6, and genotyping results showed apparent variation in allele frequency between Chinese indigenous and western breeds.

Characterization of the porcine p65 subunit of NF-κB and its association with virus antibody levels.

NF-κB p65 subunit plays important roles in controlling both innate and adaptive immunity. Here we report the characterization of porcine NF-κB p65 subunit (pp65). pp65 shows high similarity to other mammalian counterparts. pp65 mRNA expression was mainly observed in lung, spleen, liver and small intestine. Furthermore, overexpression of pp65 activates NF-κB in porcine endothelial cell line PIEC, porcine alveolar macrophages cell line 3D4/21 and porcine primary fetal fibroblasts. A COOH-terminal truncation derivative of pp65 (pp65RHD) has been identified as a specific transdominant inhibitor of NFκB. Association study was performed on the selected SNP and indel. The results revealed that the SNP BglI was significantly associated (P<0.05) with pig reproduction and respiratory syndrome virus antibody level (PRRSV-AB) (0 day and 17 days), the classical swine fever virus (CSFV) antibody blocking rates (CSFV-AB) (0 day and 17 days) and pseudorabies virus antibody level (PRV-AB) (0 day and 32 days).

A new familial gastric cancer-related gene polymorphism: T1151A in the mismatch repair gene hMLH1.

We designed to understand the effects of the T1151A gene polymorphism in the hMLH1 gene on the pathogenesis of familial gastric cancer. Peripheral blood DNA from 113 patients with familial gastric cancer or suspected familial gastric cancer that were newly identified in the same year, along with 180 healthy subjects, was subjected to polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and DNA sequencing of exon 12 in the hMLH1 gene. Our results as following, the T1151A detection rate was remarkably higher in patients with familial gastric cancer or suspected familial gastric cancer compared to normal control patients (P < 0.05). Stratified analysis showed that there was a significant difference in the detection rate between the control group and elderly patients whose age of onset was greater than 50 years old (P < 0.05). The detection rate of patients from high-risk families were relatively high (P < 0.05). An especially significant distribution was observed in patients who had suffered precancerous diseases related to gastric cancer (P < 0.01). In conclusion, familial gastric carcinoma families in China carrying the T1151A polymorphism may have a higher risk of suffering from gastric cancer. This gene polymorphism can be used as a candidate screening index for high-risk populations.

[Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma].

OBJECTIVE: To investigate the therapeutic effect and biological changes of hepatic arterial perfusion of p53 gene via port catheter system (PCS) on advanced hepatocellular carcinoma. METHODS: A total of 48 cases of advanced hepatocellular carcinoma were divided into the experimental group (30) and the control group (18). Transiliac external artery PCS implantation was performed in all cases. p53 gene was perfused into target artery confirmed by angiography. In the experimental group, 10(12) VP of p53 gene and 20 mg OPT were employed every week as a course for 21 days. In the control group, only 20 mg OPT was used. KPS, AFP and the survival period, RECIST (response evaluation criteria in solid) tumor were analyzed. Flow cytometry (FCM) and micronucleus (MN) assay in vivo were used to detect p53 gene mutation and spontaneous micronucleus formation in peripheral blood of the experimental group. RESULTS: The experimental group were performed 1 to 8 courses. There was a significant difference with AFP level and KPS in the experimental group(P < 0.05). However there was no significant difference (P > 0.05) in the control group. After one month, survival rate of the the experimental group and the control group was 96.6% and 94.4%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After three months, survival rate of the the experimental group and the control group was 83.3% and 55.6%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After six months, survival rate of the the experimental group and the control group was 50.0% and 11.1%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After nine months, survival rate of the the experimental group and the control group was 23.3% and 0%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After twelve months, survival rate of the the experimental group and the control group was 6.67% and 0%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). The depression of p53 expression was observed in the HCC patients who were employed four times of intervention operations. The difference of p53 expression between before and after interventional rAd-p53 therapy were statistically significant (P < 0.01). The frequency of MN depressed by the rAd-p53 was seen in the patients, and the differences of the frequency of MN between before and after interventional rAd-p53 therapy were statistically significant (P < 0.05). CONCLUSION: p53 gene sequential infusion via hepatic artery is effective for advanced hepatocellular carcinoma. The biological study will play a important role in selecting the therapeutic dose and judging therapeutic efficacy by means of guiding and monitoring.

[Association of IVS10+12G>A polymorphism in hMSH2 gene with colorectal cancer in Chinese].

OBJECTIVE: To investigate the association of the single-nucleotide polymorphism (SNP) IVS10+12 G>A in hMSH2 gene with colorectal cancer in a Chinese population of Jiangsu province. METHODS: A case-control study to investigate whether this SNP affects the risk of developing colorectal cancer was conducted. Subjects included 108 colorectal cancer patients and 180 healthy individuals. Peripheral white blood cell DNA was obtained from all subjects. The hMSH2 gene IVS10+12 G>A was genotyped using a PCR-based DHPLC, the existence of IVS10+12 G>A was verified by DNA sequencing. RESULTS: The allele frequency of the IVS10+12 G>A in the hMSH2 gene in the healthy individuals was 51.7%. There was significant difference in the frequency of the IVS10+12 G>A between patients and healthy controls (P<0.05), and between familial patients and healthy controls (P<0.05). There was also significant difference of the frequency of the IVS10+12 G>A between patients younger than 50 years, and patients with high consumption of fried food and pickled vegetable and healthy controls respectively (P<0.05). CONCLUSION: This SNP may be associated with colorectal cancers in Chinese. Further investigation with larger sample size is needed.

[Mismatch repair gene hMLH1 A655G/A polymorphism and colorectal cancer].

OBJECTIVE: To investigate the etiological role of hMLH1 gene A655 polymorphism in colorectal cancer. METHODS: A case-control study was carried out, including 115 colorectal cancer patients and 135 healthy people as control. Genomic DNA was extracted from peripheral white blood cell from all the subjects. Polymorphism was detected by PCR-based DHPLC analysis and verified by DNA sequencing. RESULTS: The hMLH1 gene A655G polymorphism was detected in 3.0% of healthy people and 11.3% of colorectal cancer patients (P<0.01), and the difference was significant (P<0.01). The hMLH1 gene A655G polymorphism was detected in 8.2% of tubular adenocarcinoma or tubular-papillary adenocarcinoma and 27.8% of mucinous adenocarcinoma, which was also significant (P<0.05).Meanwhile, hMLH1 gene A655G polymorphism was not associated with age, gender and lymphatic metastasis (all P>0.05). CONCLUSIONS: The hMLH1 gene A655G polymorphism may play a role in the pathogenesis of colorectal cancer. Determination of the polymorphism may be a potential marker to predict the prognosis of colorectal cancer patients.

[Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis].

OBJECTIVE: To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli (APC) gene in 3 familial adenomatous polyposis (FAP) pedigrees and to screen large fragment deletions in the APC gene. METHODS: DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR (MSP) and DNA sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene. RESULTS: No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family. CONCLUSION: Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.