SNP discovery of PRKAB1 gene and their associations with growth traits in goats.

AMPK plays an important role in regulating the metabolism of carbohydrate, lipid and protein in an organism, and is considered to be a key regulator of cellular energy homeostasis. In recent years, attention has been drawn to AMPK subunit polymorphisms and their association with economical traits of domestic animals and fowls. PRKAB1 encodes the ß1 regulatory subunit of AMPK, and it has been reported that PRKAB1 may be applied in breeding programs of meat-type chicken. To date, the polymorphism of goat PRKAB1 gene and its associations remain unknown. In this paper, the polymorphism of PRKAB1 gene was detected in 316 goats of three breeds. A total of four novel single nucleotide polymorphisms (SNPs) of PRKAB1 gene were revealed by sequence analysis. Among them, three were in the coding region (285 C > A, 297 C > A, 309 C > T), and they were all synonymous. One was in the intron (229 A > G). The associations between polymorphic loci and the growth traits of Xuhuai and Haimen goats were analyzed, and significant associations were found in body length index and trunk index (p < 0.05) for Xuhuai breed, while no significant associations in Haimen breed. Our results provide useful information for the improvement and breeding of Chinese native goats.

ZCCHC14 regulates proliferation and invasion of non-small cell lung cancer through the MAPK-P38 signalling pathway.

ZCCHC14 is a CCHC-type zinc finger protein which is expressed in tissues in human and mouse. The function of ZCCHC14 in tumours remains unclear. In this research, we explored the expression, function and related molecular mechanisms of ZCCHC14 in human non-small cell lung cancer (NSCLC). Immunochemistry staining showed that ZCCHC14 was low-expressed or absent in NSCLC tissues. In NSCLC patients, the low expression of ZCCHC14 in tumour tissues was significantly correlated with TNM stage, differentiation degree and adverse clinical outcome (P < .05). The proliferation and invasion ability of cancer cells transfected with ZCCHC14 CRISPR/Ca9 KO plasmids was significantly enhanced (P < .05). Immunoblotting analysis indicated that the expression of p-P38, cyclinD1 and MMP7 were significantly up-regulated after disabling ZCCHC14 (P < .05). We used MAPK-P38 pathway inhibitor doramapimod (BIRB 796) to inhibit P38 signalling pathway activity and determined that the agent significantly disrupted the function of ZCCHC14 and hindered the proliferation and invasion of the tumour. The finding revealed that ZCCHC14 can regulate proliferation and invasion of NSCLC through the P38 pathway. ZCCHC14 plays a crucial regulatory role in the development of NSCLC and may become a zinc finger target for clinical treatment.

Distribution characteristics and influencing factors of homocyteine in an apparently healthy examined population.

BACKGROUND: Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. METHODS: Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). RESULTS: Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P < 0.001), and the proportion of males, smoking, and drinking were higher than the low-Hcy group, the difference was statistically significant (P < 0.001); Hcy of the abnormal GLU group is higher than the normal GLU group (P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P < 0.001); Hcy of people with abnormal UA and Urea was higher than that of people with normal renal function (P < 0.001, P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (ß = - 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (ß = 0.055, SE = 0.016, P < 0.001), lnUA and lnHcy were positive correlated (ß = 0.043, SE = 0.019, P = 0.022). CONCLUSION: Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

MTNR1B gene on susceptibility to gestational diabetes mellitus: a two-stage hospital-based study in Southern China.

Large-scale studies on genetic risk loci for melatonin receptor 1B (MTNR1B) gene and GDM risk have not been well generalized to the Chinese population. In this study, we performed two-stage case-control study: 1.429 pregnant women: 753 GDM/676 controls in the Southern Chinese population by genotyping 5 SNPs (rs10830963, rs1387153, rs2166706, rs1447352, and rs4753426) in MTNR1B. Genotypes were determined using the Sequenom MassARRAY platform and TaqMan allelic discrimination assay. Interactions between genetic variants and age/BMI as predictors of GDM risk were evaluated under the logistic regression model. In the first stage, the SNP rs10830963 was discovered to be potentially related to GDM risk (additive model: OR = 1.27, 95%CI = 1.05-1.55, P = 0.025), which was further confirmed in the second stage with a similar effect (additive model: OR = 1.53, 95%CI = 1.19-1.98, P = 0.005). In the combined stage, the G allele of rs10830963 was potentially associated with GDM risk (additive model: OR = 1.36, 95%CI = 1.17-1.59, P < 0.001; dominant model: OR = 1.45, 95%CI = 1.15-1.83, P = 0.005). The rs10830963 interacted with age and BMI to contribute to GDM risk in the combined participants. And, the similar interactive effects for the other four SNPs also exist. These findings offer the potential to improve our understanding of the etiology of GDM, and particularly of biological mechanisms.

Zbed3 promotes proliferation and invasion of lung cancer partly through regulating the function of Axin-Gsk3ß complex.

Our previous work showed that Zbed3 is overexpressed in nonsmall cell lung cancer and that down-regulation of Zbed3 inhibited ß-catenin expression and cancer cell proliferation and invasiveness. Here, we investigated Zbed3's ability to promote lung cancer cell proliferation and invasion and the involvement of the Axin/TPC/glycogen synthase kinase 3ß (Gsk-3ß) complex to the response. Coimmunoprecipitation assays showed that wild-type Zbed3 bound to Axin but a Zbed3 mutant lacking the Axin binding site did not. In A549 and H1299 lung cancer cells, Zbed3 overexpression promoted cancer cell proliferation and invasiveness, as well as Wnt signalling and expression of downstream mediators, including ß-catenin, cyclin D1 and MMP7 (P < 0.05). In contrast, the Zbed3 mutant failed to enhance ß-catenin expression (P > 0.05), and its ability to promote cancer cell proliferation and invasiveness was much less than wild-type Zbed3 (P < 0.05). The ability of Zbed3 to increase ß-catenin levels was abolished by Axin knockdown in A549 cells (P > 0.05). Similarly, treating the cells with a GSK-3ß inhibitor abolished Zbed3's ability to increase ß-catenin levels and Wnt signalling. These results indicate that Zbed3 enhances lung cancer cell proliferation and invasiveness at least in part by inhibiting Axin/adenomatous polyposis coli/GSK-3ß-mediated negative regulation of ß-catenin levels.

ZCCHC9 promotes proliferation and invasion of lung cancer through regulating the JNK pathway.

ZCCHC9 is a type of CCHC type zinc-finger containing protein which was found to be expressed in some tissues including brain and testicles in mice. Expression and function of ZCCHC9 in human tissues including cancer was largely unknown. In this study, we investigated the expression and function of ZCCHC9 in human non-small cell lung cancer (NSCLC) and the related molecular mechanism. Immunochemistrical standing showed that ZCCHC9 was mainly located in the nucleus in bronchial epithelial cells and epithelial cells of submucosal glands (58.3% [14/24]). But in NSCLC cells ZCCHC9 was mainly located in the cytoplasm and the positive rate was 54.5% (60/110). Ectopic cytoplasmic expression of ZCCHC9 in cancer tissues was significantly associated with advanced TNM stages (III+IV), lymph node metastasis, and poor clinical outcome (P < 0.05). Overexpression of cytoplasmic ZCCHC9 using transfection of ZCCHC9 cDNA in A549 and NCI-H1299 cells significantly upregulated the proliferation and invasion of these cancer cells in vitro (P < 0.05). Western blot study showed that overexpression of cytoplasmic ZCCHC9 significantly upregulated expression of p-JNK, Cyclin D1, and MMP7 (P < 0.05). Next we used the inhibitor of JNK pathway to inhibit the activity of the JNK pathway and the results showed that co-addition of SP600125 significantly abolished the function of ZCCHC9 to promote the proliferation and invasion of cancer cells. These results indicate that cytoplasmic ZCCHC9 could promote the proliferation and invasion of NSCLC through the JNK pathway and may be a promising cancer maker.

The function of BED finger domain of Zbed3 in regulating lung cancer cell proliferation.

Zbed3, a BED finger domain-containing protein was found to promote cancer proliferation by regulating ß-catenin expression through interacting with Axin. But whether and how BED finger domain function in regulating cancer proliferation is unknown. We constructed five mutants of Zbed3, which lacks the Axin-Zbed3 binding site, and the 43 to 52, 69 to 77, 87 to 92, and 97 to 104 sequences in BED finger domain, respectively and named them as Z-A, Z1, Z2, Z3, and Z4. Transfection of both wild-type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05), but not Z2 (P > 0.05) significantly upregulated ß-catenin expression in NCI-H1299 cells. Overexpression of both wild-type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05) but not Z2 (P > 0.05) significantly promoted cancer cell proliferation and invasion. The ability of proliferation (P < 0.05) but not invasion (P < 0.05) of cancer cells transfected with Z1 and Z4 was significantly lower than that with wild-type Zbed3 and Z3. Overexpression of wild-type Zbed3 (P < 0.05) but not the mutant Z-A, which lacks the binding site with Axin and Z2 (P > 0.05) significantly upregulated the interaction of Axin and Zbed3, ß-catenin expression and the activity of Wnt signaling. Both overexpression of wild-type Zbed3 and the mutant Z1 and Z4 significantly upregulated the activity of Wnt signaling and promoted cancer cell proliferation (P < 0.05) but only overexpression of wild-type Zbed3 (P < 0.05), but not the mutant Z1, and Z4 (P > 0.05), significantly upregulated the expression of proliferating cell nuclear antigen (PCNA) in NCI-H1299 cells. These results indicate that Zbed3 may promote lung cancer cell proliferation through regulating PCNA expression besides regulating ß-catenin expression and BED finger domain can impact on this function.

An LC-MS/MS assay with a label-free internal standard for quantitation of serum cystatin C.

Cystatin C is considered as an alternative to the evaluation of glomerular filtration rate. In this study, we highlighted an LC-MS/MS approach for the absolute quantitation of serum cystatin C based on label-free internal standards. A tryptic peptide (ALDFAVGEYNK) was selected as the surrogate whilst analogue (ALDFAVGEYQK) served as an internal standard. After denaturation, reduction, alkylation, digestion and concentration, the target peptides were separated on an LC column and monitored under MRM. The calibration range was from 0.25 mg/L to 15 mg/L with LLOQ of 0.05 mg/L and LOD of 0.03 mg/L, respectively. The certified reference material (ERM-DA471) was determined at 5.12 mg/L with bias of 6.57%. The recovery was between 89.68% and 92.43%. The RSD of intra- and inter-assay imprecision were both <10%. Good stability was also observed. The assay also demonstrated that the quantification of native cystatin C in human serum could be achieved using label-free internal standards. The assay was robust, cheap and sensitive.

Hes3 Enhances the Malignant Phenotype of Lung Cancer through Upregulating Cyclin D1, Cyclin D3 and MMP7 Expression.

Hes3 is a basic helix-loop-helix factor gene, which was found to be involved in neural cell differentiation. Expression and clinicopathological significance of Hes3 in non-small cell lung cancer was not clear. In this study, we used immunohistochemistry to examine Hes3 expression in normal human lung and non-small cell lung cancer tissues. Hes3 expression was detected in cytoplasm and nucleus. Hes3 expression in bronchial epithelial cells and epithelial cells of submucosal glands was relatively weak and the positive rate was of 30.3% (10/33). Hes3 expression in non-small cell lung cancer tissues (51.8% (58/112)) was significantly higher than that in normal lung tissues (p < 0.05). Hes3 expression in cancer tissues was significantly associated with poor differentiation, advanced TNM stages, lymph node metastasis, and a shorter patient survival time (p < 0.05). In vitro study showed that overexpression of Hes3 in A549 cells significantly promoted cancer cell proliferation and invasion, while inhibition of Hes3 expression significantly downregulated cancer cell proliferation and invasion (p < 0.05). Western blotting showed that overexpression of Hes3 significantly upregulated expression of Cyclin D1, Cyclin D3, and MMP7 in A549 cells, while inhibition of Hes3 expression in LK2 cells significantly downregulated the expression of these molecules (p < 0.05). These results indicated that Hes3 may contribute to the malignant phenotype of non-small cell lung cancer, possibly through regulation of Cyclin D1, Cyclin D3, and MMP7, and may be a promising cancer marker.

Endometriosis in the rectum accompanied by hemorrhoids leading to diagnostic pitfalls: a rare case report.

BACKGROUND: Hemorrhoid is a common anorectal disease. Hemorrhoids accompanied by endometriosis are unusual. As endometriosis in the rectum may mimic many other diseases, including cancer and inflammation, its diagnosis may be difficult, especially when it is combined with other diseases. CASE PRESENTATION: Here, we present a rare case of a patient with hemorrhoids accompanied by endometriosis in the rectum. The endometriosis mass was detected by digital rectal examination and CT scan and confirmed by pathological examination. The mass was approximately 0.8 cm × 0.6 cm and located in the muscularis and submucosa of the rectum 8 cm from the anus. CONCLUSIONS: In this case, hemorrhoid is a common disease of rectum and anal canal. However, when it is complicated by another rare disease, the rare one can be easily neglected because of the existence of the common one, especially when the two diseases have similar lesions or symptoms. We suggest that strict physical examination, such as the digital rectal examination in the current case, is critical for correct disease diagnosis.

Sellar and suprasellar granular cell tumor of the neurohypophysis: A rare case report and review of the literature.

Granular cell tumors of the neurohypophysis are rare tumors with a WHO grade of I. Symptomatic tumors are even more rare. In this case, we present a 50-year-old patient with a sellar and suprasellar granular cell tumor of the neurohypophysis, who reported headaches, blurred vision and unsteady gait. CT imaging showed a sellar and suprasellar mass approximately 2.9 cm in diameter with clear boundaries. Histologically, the tumor lacked any obvious atypia and contained densely arranged polygonal tumor cells with abundant granular eosinophilic cytoplasm. Staining for Alpha-1 AntiChymotrypsin (AACT), TTF-1 and PAS was diffusely positive, and S-100 staining was focally positive in the tumor cells. CD34, CK, EMA, GFAP and HMB45 staining were negative. The Ki-67 index was < 1%. According to these findings, the tumor was diagnosed as a symptomatic granular cell tumor of the neurohypophysis. We suggest that identifying the location of the tumor with imaging is helpful for understanding the granular cell tumor of the neurohypophysis. Prompt diagnosis and treatment are critical for patients.

A metastasized hepatocellular carcinoma in the capsule of an undescended testis in the right inguinal area: report of a rare case.

BACKGROUND: Hepatocellular Carcinoma (HCC) is the most common primary carcinoma of the liver, which mainly metastasizes through the portal vein system. CASE PRESENTATION: Here, we report an extremely rare case in which HCC metastasized to the capsule of an undescended testis in the right inguinal area of the patient. A tumor approximately 8.8 × 7.0 cm in size was found in the patient's liver during a health check-up. Initially, it was considered a metastatic tumor because the patient was found to have cryptorchidism, which had been left untreated before he presented to our hospital. The patient underwent a radical orchiectomy via inguinal approach, and the resected testis in the right inguinal region was examined via microscopy. The cancer cells were arranged in nests and showed abundant red or clear cytoplasm and marked nuclear atypia. Immunohistochemical staining showed that the tumor cells were positive for CK, CK8/18, AFP, hepatocyte, GCP3, but negative for PLAP, CD10, CD30, CD34, and vimentin. CONCLUSION: According to these findings, the tumor in the inguinal region was considered a metastatic HCC arising from the liver, rather than a seminoma that had originated in the undescended testis. We suggest that during the diagnosis of malignancies, metastatic tumors should always be considered in the differential diagnosis even if the original presentation is at rare metastatic sites or concurrent with other disease(s).

Human circular RNA hsa_circ_0000231 clinical diagnostic effectiveness as a new tumor marker in gastric cancer.

BACKGROUND: Owing to the subtlety of initial symptoms associated with gastric cancer (GC), the majority of patients are diagnosed at later stages. Given the absence of reliable diagnostic markers, it is imperative to identify novel markers that exhibit high sensitivity and specificity. Circular RNA, a non-coding RNA, plays an important role in tumorigenesis and development and is well expressed in body fluids. AIMS: In this study, we aimed to identify hsa_circ_0000231 as a new biomarker for the diagnosis of GC and to assess its clinical diagnostic value in serum. METHODS AND RESULTS: The stability and correctness of hsa_circ_0000231 was determined by agarose gel electrophoresis, Rnase R assay and Sanger sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was designed to discover the expression level of hsa_circ_0000231 and whether it has dynamic serum monitoring capability. The correlation between hsa_circ_0000231 and clinicopathological parameters was analyzed by collecting clinical and pathological data from GC patients. In addition, diagnostic efficacy was assessed by constructing receiver operating characteristic curves (ROC). Hsa_circ_0000231 exhibits a stable and consistently expressed structure. In GC serum, cells, and tissues, it demonstrates reduced expression levels. Elevated expression levels observed postoperatively suggest its potential for dynamic monitoring. Additionally its expression level correlates with TNM staging and neuro/vascular differentiation. The area under ROC curve (AUC) for hsa_circ_0000231 is 0.781, indicating its superior diagnostic value compared to CEA, CA19-9, and CA72-4. The combination of these four indicators enhances diagnostic accuracy, with an AUC of 0.833. CONCLUSIONS: The stable expression of hsa_circ_0000231 in the serum of gastric cancer patients holds promise as a novel biomarker for both the diagnosis and dynamic monitoring of GC.

A portable CRISPR-Cas12a triggered photothermal biosensor for sensitive and visual detection of Staphylococcus aureus and Listeria monocytogenes.

The detection of foodborne pathogens is crucial for ensuring the maintenance of food safety. In the present study, a portable CRISPR-Cas12a triggered photothermal biosensor integrating branch hybrid chain reaction (bHCR) and DNA metallization strategy for sensitive and visual detection of foodborne pathogens was proposed. The sheared probes were utilized to block the locker probes, which enabled preventing the assembly of bHCR in the absence of target bacteria, while target bacteria can activate the cleavage of sheared probes through CRISPR-Cas12a. Therefore, the locker probes functioned as initiating chains, triggering the formation of the branching double-stranded DNA consisting of H1, H2, and H3. The silver particles, which were in situ deposited on the DNA structure, functioned as a signal factor for conducting photothermal detection. Staphylococcus aureus and Listeria monocytogenes were selected as the foodborne pathogens to verify the analytical performance of this CRISPR-Cas12a triggered photothermal sensor platform. The sensor exhibited a sensitive detection with a low detection limit of 1 CFU/mL, while the concentration ranged from 100 to 108 CFU/mL. Furthermore, this method could efficiently detect target bacteria in multiple food samples. The findings demonstrate that this strategy can serve as a valuable reference for the development of a portable platform enabling quantitative analysis, visualization, and highly sensitive detection of foodborne bacteria.

YY1-induced LncRNA-TUG1 elevates YOD1 to promote cell proliferation and inhibit bortezomib sensitivity in multiple myeloma.

Taurine upregulated gene 1 (TUG1) has been implicated in the onset and progression of various malignancies. The current study aimed to evaluate the biological function and potential mechanisms of TUG1 in multiple myeloma (MM) progression. TUG1 knockdown in MM cells was investigated in vitro and in vivo to evaluate the role of TUG1. We also predicted the transcription factor (TF) that bound to TUG1 together with the downstream target genes of the TUG1-TF interaction, and evaluated the regulatory mechanism of TUG1 in cell assays. TUG1 knockdown reduced the cell's proliferative and migratory capabilities while increasing apoptosis and bortezomib sensitivity in vitro and inhibiting tumorigenesis in vivo. TUG1 was found in the nucleus of MM cells and was found to be positively regulated by the TF-YY1. Further in vitro mechanistic investigations indicated that the YY1-TUG1 complex targeted YOD1 to regulate MM progression.

Polymorphisms of diacylglycerol acyltransferase 2 gene and their relationship with growth traits in goats.

Diacylglycerol acyltransferase (DGAT) plays a critical role in the synthesis of triacylglycerol. In this study, PCR-SSCP and DNA sequencing methods were employed to screen the genetic variations of DGAT-2 gene in 299 goats from three breeds (Boer goat, Chinese Xuhuai white goat and Chinese Haimen goat). Three fragments of DGAT-2 gene were investigated, only exon 3 of DGAT-2 gene showed polymorphism. The alignment between nucleotide sequences of NM_205793.2 in GenBank and the sequencing results of three PCR products with different patterns revealed that there was one mutation (A → G) in exon 3 of DGAT-2 gene, which resulted in amino acid change (Lys → Arg) and constructed two genotypes (AA, AB). The frequencies of allele A and genotype AA were dominant in all three breeds. And there was no significant difference for genotypic and allelic frequencies among the three breeds. The genotype distributions were in good agreement with Hardy-Weinberg equilibrium (P > 0.05) in each breed. Significant statistical differences were only found in withers heights (P < 0.05) in Xuhuai goat between genotypes. The results indicated that individuals with genotype AA were significantly higher than those of individuals with genotype AB in withers height (P < 0.05). No polymorphism was detected in the intron 3, exon 8 and 3' flanking region. So we suggested that DGAT-2 gene had the close relationship with growth traits in goats. And this mutation could be used as a perfect molecular marker for marker-assisted selection (MAS) in animal genetics and breeding.

The Mobile Phone Addiction and Depression Among High School Students: The Roles of Cyberbullying Victimization, Perpetration, and Gender.

Objective: To examine the relation between mobile phone addiction and high school students' depression, and its inner mechanism-the sequential mediating roles of the cyberbullying victimization and the cyberbullying perpetration in this relationship. Methods: 1297 high school students were recruited to complete the Smartphone Addiction Scale, European Cyberbullying Intervention Project Questionnaire and the Center for Epidemiological Studies Depression Scale. Results: (1) Mobile phone addiction was positively correlated with and high school students' depression; (2) cyberbullying victimization and the cyberbullying perpetration significantly mediated the relation between mobile phone addiction and high school students' depression, which contained tow mediating paths-the independent mediating effects of cyberbullying victimization and the sequential mediating effect of cyberbullying victimization and the cyberbullying perpetration; (3) there are gender differences in the sequential mediation model, and boys who are victims of cyberbullying are more likely to develop into cyberbullying perpetrators than girls. Conclusion: The results of this study indicate that depression among high school students with mobile phone addiction can be eliminated through the development of cyberbullying victimization and the cyberbullying perpetration.

Polymorphism in a microsatellite of the acrp30 gene and its association with growth traits in goats.

Acrp30 plays a critical role in the regulation of glucose and lipid homeostasis. In this study, polymorphism of the Acrp30 gene was detected by PCR-SSCP and DNA sequencing methods in 321 individuals from three goat breeds, and the association of Acrp30 gene polymorphism with growth traits in the three goat breeds was analyzed. A novel insert/deletion (GT)(5) microsatellite sequence was detected in the 5' flanking region of the gene. Three genotypes (AA, AB, and BB) were found in three breeds. There was moderate genetic diversity in the locus in the analyzed populations. Significant associations were observed between the genotypes of the locus and growth traits in the Boer goat population. The chest circumference of individuals with genotype BB was significantly greater than that of individuals with genotype AA.

Serum hsa_circ_0087776 as a new oncologic marker for the joint diagnosis of multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy caused by abnormal proliferation of bone marrow plasma cells, which lacks diagnostic markers and has a general prognosis. At present, the understanding of its pathogenesis provides the basis for the combined diagnosis and new targeted therapy of the disease. In this study, quantitative real-time PCR was used to detect 136 MM patients and 74 healthy controls, and the clinical application value of hsa_circ_0087776 as a new tumor marker and combined diagnosis was evaluated. The results showed that the expression of hsa_circ_0087776 was significantly lower in serum of MM patients (P-value < 0.0001), and the expression was consistent in MM cells. In the analysis of clinicopathological parameters, it was found that there were significant statistical differences with MM stage and renal injury. In addition, it significantly increased the sensitivity with ALB, ß2-MG joint diagnosis, to provide a basis for diagnosis, improve the prognosis of the disease, improve the survival of patients and quality of life. These studies suggest that hsa_circ_0087776 can be used as a new oncology marker for the combined diagnosis of MM.Impact statement: Various evidences have shown that the role of circRNA in the occurrence and development of diseases is potentially unknown and untapped. Therefore, it has a broad prospect to find circRNA specifically expressed in MM patients for combined diagnosis and targeted therapy of MM. However, MM lacks such specific tumor markers. Therefore, the discovery of new specific tumor markers for combined diagnosis is an important milestone in the development of medical history. In the research, we founded hsa_circ_0087776 can be used as a new oncology marker for combined diagnosis of MM.

Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents.

Mimicking the nitric oxide (NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis (ISR) effectively. However, the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component. Herein, we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species (e.g., Cu-DOTA coordination complex) and glycocalyx-like component (e.g., heparin) to create a durable endothelium-mimicking surface. The stent surface was firstly coated with polydopamine (pDA), followed by a surface chemical cross-link with polyamine (pAM) to form a durable pAMDA coating. Using a stepwise grafting strategy, Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry. Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules, this proposed strategy could provide 62.4% bioactivity retention ratio of heparin, meanwhile persistently generate NO at physiological level from 5.9 ± 0.3 to 4.8 ± 0.4 × 10-10 mol cm-2 min-1 in 1 month. As a result, the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis, inflammation, and intimal hyperplasia, enhanced re-endothelialization, and hence efficiently reduced ISR.